Blackwell Publishing LtdOxford, UKBIJBiological Journal of the Linnean Society0024-4066The Linnean Society of London, 2006? 2006
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655672
Original Article
GENOMIC CREATIVITY AND NATURAL SELECTION
F. P. RYAN
Biological Journal of the Linnean Society, 2006, 88, 655–672. With 1 figure
Genomic creativity and natural selection: a modern
synthesis
FRANK P. RYAN*
Sheffield South-West Primary Care Trust, 5 Old Fulwood Road, Sheffield S10 3TG, UK
Received 14 December 2004; accepted for publication 5 December 2005
In the early 1930s, the synthesis of Darwinian natural selection, mutation, and Mendelian genetics gave rise to the
paradigm of ‘modern Darwinism’, also known as ‘neo-Darwinism’. This has contributed greatly to our understanding.
But increasing knowledge of other mechanisms, including endosymbiosis, genetic and genomic duplication, polyploidy, hybridization, epigenetics, horizontal gene transfer in prokaryotes, and the modern synthesis of embryonic
development and evolution, has widened our horizons to a diversity of possibilities for change. All of these can be
gathered under the umbrella concept of ‘genomic creativity’, which, in partnership with natural selection, affords a
more comprehensive modern explanation of evolution. © 2006 The Linnean Society of London, Biological Journal
of the Linnean Society, 2006, 88, 655–672.
ADDITIONAL KEYWORDS: biological species concept – gene splicing – neo-Lamarckism – phenotypic selection – saltationism – viral symbionts.
INTRODUCTION
As recently as 1998, the highly respected Ernst Mayr
stated: ‘The young biologist of today . . . knows that
gene mutations are the only raw material of evolution’
(Mayr, 1998). A similar viewpoint is expounded in a
popular textbook (Hartl & Jones, 1998) and in the otherwise laudable review by Endler & McLellan (1988),
for whom mutation is a catch-all including gene duplication, transposable elements, and ‘hybrid dysgenesis’. Why, when there is so much evidence to the
contrary, do many knowledgeable biologists still insist
that mutation is the exclusive raw material of evolution? As Rudolf A. Raff, professor of biology at Indiana
University and a leading thinker in evolutionary
development, remarks: ‘Our attitudes towards the
great problems of biology are conditioned by historical
contingencies’ (Raff, 1996).
MUTATION
Darwin (1859) was well aware that natural selection
required hereditable variation to choose from,
although he was uncertain as to how such variation
*Corresponding author. E-mail: [email protected]
arose. In retrospect, this was often attributed to his
failure to grasp Mendelian inheritance (Mendel,
1866), but Mendelism alone would not have provided
him with a sufficient source of novelty. During his lifetime there were reservations about Darwin’s theory
from within the mainstream of biology and, after his
death in 1882, these doubts gathered momentum. In
the words of Julian Huxley, introducing the synthesis
concept in 1942: ‘The really important criticisms have
fallen upon natural selection as an evolutionary principle, and have centred round the nature of inheritable
variation’ (Huxley, 1942: 17). So it was that, in the
opening years of the 20th Century, such criticisms provoked a period of crisis that Huxley labelled ‘the
eclipse of Darwinism’, a term that was subsequently
borrowed by Bowler for the title of his book (Bowler,
1992). The first convincing explanation of variation
came from De Vries proposal of mutation (De Vries,
1906), which, when amalgamated with Mendelian
inheritance, provided the raw material for natural
selection in the new all-embracing synthesis. This
rationalization came about in the 1930s as a result of
a gradual accumulation of ideas from many authorities, including Chetverikov (1926) in the Soviet Union;
Fisher (1930) and Haldane (1932) in Britain; and
Wright (1931) and Dobzhansky (1937) in the United
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
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F. P. RYAN
States of America. Variously known as ‘modern Darwinism’ or ‘neo-Darwinism’, it had an enormous influence on the biological sciences.
Johannsen had previously defined the concepts of
phenotype and genotype, while incidentally coining
the term gene (Johannsen, 1911). Meanwhile, geneticists, in particular Morgan and his group (Morgan,
1911), had confirmed both the nature of genes and the
reality of mutations. With the elucidation of the molecular structure of DNA (Watson & Crick, 1953), genes
were identified as individual packets, or ‘cistrons’, of
nucleotide sequences that were perceived both to store
hereditary information and to act as templates for the
translation of this information to the amino acid
sequences in the corresponding polypeptide chains.
Today, we know that evolutionary processes are more
complex than they appeared in the 1930s and that
selection can operate at a number of different levels,
both genetic and phenotypic. Recently, a number of
biologists, disaffected with what they perceive as the
failings of the gene-centred mutation-plus-selection as
the explanation of evolution, have rebelled in various
ways (Goodwin, 1994; Lewontin, 1998; WestEberhard, 2003; Jablonka & Lamb, 2005). This has
been further complicated by the abandonment of the
one-gene–one-protein concept. Individual genes are
made up of a number of exons, separated by noncoding
introns, and the shuffling of exons from one or more
genes, contributes to the coding of different proteins,
through ‘alternative splicing’ (Gilbert, 2003). Known
as ‘splicing isoforms’, these are a frequent finding in
the human genome (Croft et al., 2000). To illustrate
the extremes to which this can operate, the current
record goes to the Drosophila Dscam gene (this plays a
fundamental role in guiding axons to their targets
during nervous system development), which contains
24 exons, translating, in theory, to some 38 000 potential proteins (Gilbert, 2003). Nevertheless, for most
biologists, the basic tenets of evolution still pertain,
even if they need some extrapolation and readjustment to embrace all mechanisms for change. Evolution derives from genomic (not solely genetic) novelty,
under the influence of natural selection, the latter, at
the population level, introducing various constraining,
adaptive, rate-determining and direction-determining
influences (Endler & McLellan, 1988) that link phenotypic and, ultimately, genomic change to the living
environment.
Mutations are defined as a source of novelty arising
from errors in copying the nucleotide sequences of
DNA. There are many different types of mutation,
classified by function (Hartl & Jones, 1998), but the
most important discrimination is between mutations
that affect structural genes and those that affect
developmental pathways. Mutations that change
developmental pathways are of particular importance
to the evolution of anatomical form. Muller called
these ‘neomorphic mutations’ because they cause the
expression of a developmental gene at a time when the
wild-type (normal) gene is not normally expressed. In
Drosophila, for example, ectopic expression of the gene
known as ‘eyeless’ results in parts of compound eyes,
complete with pigments, in abnormal locations, such
as on the antennae or on the wings. Other mutations
are known to affect developmental pathways in a more
quantitative way. A recent discovery by Karen Sears
and colleagues at the University of Colorado, suggests
that change in the expression pattern of a gene known
as BMP2 drives the elongation of digits during bat
development (Hecht, 2004; Sears, Behringher &
Niswander, 2004). BMP2 is expressed at a much
higher level in the growth plates of bats than in those
of other mammals (K. E. Sears, pers. comm.). Bat
wings appear suddenly in the fossil record, suggesting
that the necessary change, assumed to be a mutation
in the developmental pathways for BMP2, happened
in a relatively short time period, geologically
speaking.
In the words of the pioneering evolutionary biologist
Eric H. Davidson, the synthesis theory of mutationplus-selection ‘has generated a vast calculus for analysing adaptive and selective processes’ (Davidson,
2001). Many familiar concepts have derived from this,
including fitness, selection pressure, population genetics, selfish gene thinking (Dawkins, 1976), punctuated
equilibrium (Gould & Eldredge, 1977), and the
systematics of phylogeny and cladistics. It is hardly
surprising that many biologists have come to regard
mutation-plus-selection as the exclusive explanation
of evolution. However, this has come under pressure
from a growing litany of alternative mechanisms of
genomic creativity that requires not so much a
revolution in theory as a widening of conceptual
understanding.
SYMBIOSIS
Some 319 species of hummingbirds live almost
entirely on nectar, a dependence that has led to specialized joints in their wings that enable them to hover
with pinpoint accuracy over the appropriate flower.
Flower and bird are partners in a mutualistic
exchange of food for the bird and assistance with fertilization for the flower. In an even tighter partnership, at least one quarter of all described fungi, an
estimated 12 000–20 000 species, enter into associations with 40 genera of photosynthetic algae to form
some 13 500 species of lichens. This strategy is so successful that lichens are the most enduring and widespread of life forms. We classify such partnerships as
‘symbioses’, a term first defined by de Bary in 1878 as
‘the living together of differently named organisms’
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GENOMIC CREATIVITY AND NATURAL SELECTION
(Sapp, 1994). His definition included parasitism, commensalism and mutualism. Implicit was the role of
symbiosis as a force in evolution, which was subsequently conceptualized with the term ‘symbiogenesis’
(Merezhkovskii, 1910).
Symbiogenesis does not contradict Darwinism but it
differs from the mutation-plus-selection paradigm of
neo-Darwinism in several respects. A symbiosis begins
when two or more dissimilar species come together to
pool pre-evolved traits, genes or even whole genomes.
Natural selection does not create the symbiosis de
novo but it edits the partnership once it has become
established. For example, selection has shaped the columnia flower and the bill of the hummingbird to fit
one another, thus developing and stabilizing the relationship. This is an example of an ‘exosymbiosis’ (also
known as ‘ectosymbiosis’). A more powerful form of
symbiosis is known as ‘endosymbiosis’. In Mayr’s opinion, the evolutionary transition from bacterium to the
eukaryotic cell was the single most important step in
the history of life. In 1970, Lynn Margulis theorized
that the first nucleated cells were created by the serial
fusion, or ‘endosymbiosis’, of pre-existing prokaryotes
(Margulis, 1970). One such endosymbiont gave rise to
mitochondria, which still retain residual prokaryotic
DNA. Rickettsia prowazeki, an obligate intracellular
parasite and the cause of epidemic typhus, is the closest known α-proteobacterium to the single ancestor of
all present-day mitochondria (Andersson et al., 1998;
Gray, 1998). An independent series of endosymbiotic
unions with various photosynthetic microbial partners
gave rise to chloroplasts, which also retain varying
amounts of residual DNA (Ryan, 2002/2003).
Bermudes & Margulis (1987) have proposed that the
evolution of 27 of the 75 phyla in the classification of
Margulis & Schwartz (1998) and many lesser taxa
involved the symbiotic incorporation of organelles that
had once been free-living microbes, including Cnidaria, Acanthocephala, Pentastoma, and Ventimentifera. Symbiogenesis also contributed to the evolution
of mycorrhizal plants, which amount to some 97% of
all terrestrial varieties, as well as 15 protist and two
fungal phyla. It also contributed to the evolution of
legumes with their nitrogen-fixing rhizobial bacteria,
many wood-eating cockroaches and termites, ruminant mammals, and luminous fish. John Maynard
Smith and Eörs Szathmáry, who looked at symbiogenesis from a Darwinian perspective, concluded that it
has played an important role in three of their ‘five
major transitions’ that led to the evolution of biodiversity (Maynard Smith & Szathmáry, 1995, 1999).
The very vagueness of De Bary’s original definition
has proven useful in embracing the diverse manifestations of symbiosis, but it has proved problematic in
its extrapolation to modern concepts of symbiogenesis.
To clarify this, I redefined symbiogenesis:
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Symbiogenesis is evolutionary change arising from the interaction of different species. It takes two major forms: endosymbiosis, in which the interaction is at the level of the genomes,
and exosymbiosis, in which the interaction may be behavioural
or involve the sharing of metabolites, including gene-coded
products (Ryan, 2002/2003).
Where behavioural exosymbioses, such as pollination
mutualisms, imply a certain degree of physical contact, metabolic exosymbioses do not require intimate
contact, merely the sharing of metabolites. Meanwhile, the creativity of endosymbiosis is given clear
and separate emphasis. Endosymbiosis is viewed as a
mechanism for saltatory change arising from the
immediate sharing of pre-evolved genes, and is seen at
its most powerful in the blending of whole genomes.
Increasing study at the genomic level has revealed
the complex nature of many endosymbioses. For example, the nodulation and fixation genes of the rhizobia,
Mesorhizobium loti, are encoded on the bacterial chromosome in the form of a 500-kb ‘symbiosis island’ that
can be transferred from a symbiotic to nonsymbiotic
strain of mesorhizobia in the field due to the presence
of a P4 phage integrase that is intrinsic to the symbiosis island (Sullivan & Ronson, 1998). The subtlety
and complexity of such interactions illustrates a key
application of this redefinition of symbiogenesis,
which includes the potential of viral infection of host
germ cells as a widespread but little-explored source of
endosymbiotic creativity.
ENDOSYMBIOTIC VIRUSES
Perhaps the most familiar example of viral–eukaryotic
symbiosis is seen in the parasitoid wasps, which
include approximately 25 000 species in symbiotic
partnerships with approximately 20 000 species of
polydnaviruses. In many such examples, the viral
genome has been integrated into the wasp genome
(Whitfield, 1990). Genome sequencing of a polydnavirus has revealed a complex organization (Espagne
et al., 2004) and a conserved gene family has been
found in viruses of different wasp subfamilies, which
would fit with a common phylogenetic origin (Provost
et al., 2004). Estimations of the first establishment of
the endosymbiosis, based on mitochondrial 165 rRNA
and cytochrome oxidase subunit I genes and the
nuclear 28SrRNA gene of the polydnavirus-bearing
clade of braconid wasps, suggest a unique integration
event 73.7 ± 10 Mya (Belle et al., 2002; Whitfield,
2002), emphasizing stability over time. Such endosymbiotic unions of viruses and their hosts are far from
unusual. Indeed, it is becoming increasingly clear that
endosymbiotic unions of viruses and hosts have influenced the evolution of life throughout most, if not all,
of biodiversity.
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
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F. P. RYAN
Luis P. Villarreal is a professor in the Department of
Molecular Biology and Biochemistry and director of
the Center for Virus Research at the University of California, Irvine. The author of the viral evolution chapter in Field’s Virology, he was commissioned by the
American Society for Microbiology to write a landmark book on the implications for host evolution of the
creative power of viruses (Villarreal, 2005). Villarreal
believes that ‘host colonization harnesses the creative
power of viruses [that] create new genes from stitching together lots of smaller genes’ (L. P. Villarreal,
pers. comm.). Viral genomes have been sequenced to
analyse the evolution of their lineages. Formerly,
many biologists assumed that viruses borrowed these
genes from their hosts but, when Villarreal analysed
these lineages, he discovered that 80% of viral genes
have no counterparts in the eukaryotic genetic database, confirming that viruses are enormously creative
in the manufacture of new genes. Viruses are also
extremely creative in the manufacture of novel
regulatory and epigenetic pathways. This genomic creativity is available for subsequent virus-host endosymbiotic unions.
In pandemic form, viruses alter species gene pools
through a process that I have labelled ‘plague culling’
(Ryan, 2002/2003). In endosymbiotic form, Villarreal
& DeFilippis (2000) believe that DNA viruses may
have contributed key DNA polymerases to the eukaryotic lineage. Recent evidence points to the origin of
introns through an invasion colonization of eukaryotic
protein-coding genes by genetic parasites after their
divergence from prokaryotes (Mattick, 1994). Where
group I introns are self-splicing mobile elements and
often code for a DNA transposase protein, group II
introns code for a reverse transcriptase-like protein
and are thought to have originated in the RNA world
(Gilbert, 1986; Villarreal, 2005). These intron systems
are not characteristic of prokaryotic cells but several
are present in prokaryotic viruses and DNA viruses,
suggesting a possible viral origin (Bhattacharya,
Friedl & Damberger, 1996; Landthaler et al., 2002;
Villarreal, 2005). Villarreal and his Australian colleague, Philip Bell, have independently suggested that
a double-stranded DNA virus may have helped create
the earliest common ancestor of the eukaryotic
nucleus (Villarreal & Bell, 2001). In his book, Villarreal makes an important distinction between the consequences of ‘persistent’ as opposed to ‘acute’ viral
infections (Villarreal, 2005). Persistent viruses do not
usually follow the Lotta–Volterra models of predator–
prey relationships; they are not associated with high
level production of progeny; and, as a rule, they cause
unapparent, generally asymptomatic, infections. Such
strategies ensure the maintenance and stability of the
viral genome. In many cases, the persistent virus
becomes incorporated into the host genome. Persistent
viral infections include the temperate bacteriophages
of bacteria and the endogenous retroviruses that
infect animals and plants. In no taxon has the relationship between endogenous retroviruses and their
hosts been so extensively examined as in vertebrates,
mainly primates, and humans in particular, with
implications for human evolution, physiology and
disease.
Retroviruses have two very different life strategies.
The ‘exogenous retrovirus’, HIV1, reproduces within
the somatic tissues of infected individuals and infects
the human population through various person-to-person transmission strategies. Endogenous retroviruses
(ERVs) spread through germline transmission, their
genes replicating in Mendelian fashion as an integral
part of the sexual and cellular reproduction of the
host. Some 8% of the human genome consists of
human endogenous retroviruses, or HERVs, and,
approximately one half of our DNA comprises HERV
genes, fragments, and derivatives (Medstrand, de
Lagemaat & Mager, 2002; Bannert & Kurth, 2004).
Many HERVs are unique to humans (Barbulescu
et al., 1999). Recently, a new virus, HERV-K113, was
discovered on chromosome 19 in just 29% of people of
mainly African, Asian, and Polynesian extraction. This
suggests that it entered the human genome after the
last great migration of modern humans from Africa
(Turner et al., 2001; J. Lenz, pers. comm.). An origin
through exogenous infection is strongly suggested by
the fact that this virus, like HERV-H/RGH-2, which is
circumstantially associated with multiple sclerosis,
has not yet entirely lost its horizontal transmissibility.
However, the great majority of HERVS are no longer
infectious in the exogenous sense.
HERVs have the same genomic structure as existing exogenous retroviruses, such as HIV-1. Although
we cannot be sure that the exogenous forebears of our
human endogenous retroviruses behaved as highly
virulent infections, it appears likely that they originated as a series of mammalian, primate and hominid
pandemics, with repeated species gene pool culling.
There is some circumstantial evidence for this in primates from the comparison of mitochondrial and tissue compatibility genes in humans and chimpanzees
(Gagneux et al., 1999; Zhao et al., 2000; De Groot
et al., 2002). HERVs are the viral equivalent of the
microbial symbioses that gave rise to mitochondria
and chloroplasts. However, once viruses enter a
genome, their capacity for evolutionary innovation
remains persistently active. Millions of years after initial genomic incorporation, and despite the policing of
natural selection, endogenous retroviruses can interact with newly arrived exogenous viruses or with
other genetic components and regulatory mechanisms, thus increasing evolutionary ‘plasticity’ (Löwer,
Löwer & Kurth, 1996).
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
GENOMIC CREATIVITY AND NATURAL SELECTION
Although many HERVs have been degraded into
fragments, these can be still be recognized from their
three pathognomic genes, gag, pol, and env, and their
flanking long-terminal repeats (LTRs) (Fig. 1). These
genes are further subdivided into regions with different functions. For example one region of the env gene
codes for the surface protein of the virus while other
regions are responsible for inducing host cell fusion
and immunosuppression. Vast numbers of HERVs
have entirely lost their genes but can still be recognized from the tens of thousands of solitary LTRs that
still retain a variety of genetic potentials.
Given their interactive nature within the genome,
HERVs have obvious potential for genetic disorders
and human diseases, including interference with
fertility, autoimmune disorders, and carcinogenesis
(Ryan, 2004). The human genome is massively colonized by LTRs and the long and short interspersed
repeats, known as LINES and SINES. Investigation of
HERVs and their genomic derivatives has shed new
light on animal evolution and physiology.
In 1996, Roy J. Britten, of the California Institute of
Technology, showed ten examples in eukaryotes where
mobile elements had been inserted into gene regions
and were found to modify transcriptional control (Britten, 1996). Two of these mobile elements were the
long-chain terminal repeats of retroviruses. All such
viral elements appeared to have been preserved by
selection over long periods of time. In Australia,
Rachel O’Neill and colleagues have shown how retroviruses inhabiting the centromeres are remodelling
the chromosomes of interspecies hybrid rock wallabies, thus helping to create new species (O’Neill,
O’Neill & Graves, 1998, O’Neill, Eldredge & Graves,
2001). Meanwhile, phylogenetic and sequence analysis in humans has persuaded Hughes & Coffin (2001)
that HERVs may have induced large scale deletions,
duplications and chromosome reshuffling, thereby
playing a role in human evolution. The soviet geneticist, Eugene D. Sverdlov, also suggests that newly
integrated HERVs may have changed the pattern of
gene expression and thus played a significant role in
the evolution and divergence of the hominids (Sverdlov, 2000). HIV-1 has the capacity to fuse mammalian
cells into multinucleated inflammatory aggregates.
Fusion of cells is also a characteristic feature of the
syncytium, a key membrane of the mammalian placenta, which forms the physiological barrier between
maternal and foetal circulations. There is overwhelming evidence that several endogenous retroviruses,
5' LTR
gag
pol
env
5' LTR
Figure 1. Common genomic strcture of exogenous and
endogenous retroviruses.
659
including members of the families ERV-3, HERV-W,
and HERV-FRD, play an important role in the anatomical construction and physiological function of the
syncytium, with their env genes coding for the proteins syncytin and syncytin 2, which fuse mammalian
cells (Blond et al., 2000; Mi et al., 2000; Blaise et al.,
2003; Ryan, 2004). Rote, Chakrabarti & Stetzer (2004)
have concluded that the viral proteins syncytin, syncytin 2, and ERV-3 env play differing but essentially
complementary roles in human placentation. A less
developed endosymbiotic interaction between ERVs
and marsupial pregnancy has also been demonstrated
(Villarreal, 2005), with implications for mammalian
evolution that are both obvious and profound.
HERV LTRs contain regulatory elements that act as
promoters, enhancers, silencers, and polyadenylation
signals that may influence the cellular expression of
proteins (Dunn, Medstrand & Mager, 2003). HERVderived promoters of various potencies are frequently
found in human promoter regions. These may also
play important roles in embryological development.
For example, Andersson and colleagues have shown
that HERV-R (also known as ERV-3) is highly
expressed in many human foetal tissues, including the
adrenal cortex, kidney tubules, tongue, heart, liver,
and the central nervous system, as well as in the sebaceous glands of normal skin (Andersson et al., 1996,
2002; Ryan, 2004). Moreover, in such studies, HERV-R
has been correlated with organ-specific expression,
suggesting a role in tissue development and differentiation. There is growing evidence for similar roles for
HERVs throughout the primates. Indeed, given the
explosion of ERVs that accompanied the origins of the
vertebrates (Villarreal, 2005), it is likely that endosymbiotic endogenous viral interactions have played
integral roles in the evolution of vertebrates.
The integration of HERVs was assumed to be irreversible until Medstrand et al. (2002) showed they
could be removed, perhaps through chromosome deletions, but more likely through sexual homologous
recombination. The retention of HERVs in the human
genome must therefore involve positive selection, but
how then do we rationalize such endosymbiotic creativity with natural selection? In the opinion of the
late John Maynard Smith, there is a key difference to
how selection works in symbiogenesis compared to
neo-Darwinian evolution Maynard Smith, 1991).
Rather than, or perhaps even in addition to, operating
at an individual (or single gene) level, in symbiogenesis, ‘mutations in the genes of the symbiont will be
selected only if they increase the fitness of the host’.
But even this enlightenment fails to grasp that, in
endosymbiotic union, symbiont and host are one, in
the same way that Maynard Smith categorizes the
eukaryotic organism as a whole, ‘all of whose genes
(nuclear or cytoplasmic) will be selected to maximize
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F. P. RYAN
the inclusive fitness of the carrier’. Thus, in symbiogenesis, selection operates at the level of the partnership. This was classically demonstrated by Jeon (1991,
2004) with the union of D strain of Amoeba proteus
and Legionella-like X-bacterium in which the endosymbiotic union of amoeba and plague bacterium
stabilized within 1 year of first infection, such that
neither symbiont nor host could survive in the absence
of the other. This helps us to understand the nature of
the interaction between human endogenous retroviruses and the rest of the human genome.
When Bonnnaud et al. (2004) tracked the action of
natural selection on the 40 million-year-old HERV-W
locus, ERVWE1 (whose env gene codes for syncytin) in
chimpanzee, gorilla, orang-utan, and gibbon, they
found that a genetic sequence crucial to the gene’s
fusogenic action has been conserved by natural selection over the tens of millions of years of primate divergence. The action of negative selection at partnership
level would also help explain several other observed
features of HERVs, where attrition through gene loss
or inactivation by mutation has eliminated their original exogenous independence.
GENE AND GENOME DUPLICATION
In the same year that Lynn Margulis published her
theory of endosymbiotic origins of the eukaryotic cell,
Susumu Ohno, a geneticist working at the City of
Hope Medical Center, Duarte California, published an
equally iconoclastic theory in his book, Evolution by
Gene Duplication (Ohno, 1970). Where the presumed
ancestral prokaryotes contain a few thousand genes,
the descendent multicellular eukaryote genomes were
far larger and more complex. For example, the fruit
fly Drosophila melanogaster contains 13 600 genes
(Adams et al., 2000), the ascidian Ciona intestinalis
has 16 000 genes (Dehal et al., 2002), the sea urchin
Strongylocentrotus purpuratus has 27 350 genes
(Cameron et al., 2000), and the human genome has
been variously estimated at from 25 000 to 32 000
genes (International Human Genome Sequencing
Consortium, 2001; Venter et al., 2001). This requires
evolutionary mechanisms that increase total gene
numbers within the genome, allowing the new genes
to adapt to new physiological and developmental roles.
Ohno proposed that this had arisen through genetic,
polygenetic and even whole genome duplication. Suggested mechanisms ranged from tandem duplications
to polyploidy, which offered ‘duplication of all gene
loci . . . in one fell swoop’ (Ohno, 1970: 98). Polyploidy
can arise through a failure in one of the meiotic reduction divisions, most commonly the first, so that the
unreduced sperm, or ovum, is diploid instead of haploid. Subsequent fertilization involving permutations
of one or two diploid gametes will result in triploidy or
tetraploidy, respectively. Polyploidy can also arise
through hybridization, or sexual union of different
species. When tetraploidy derives from genome duplication in a single diploid ancestral species it is known
as autotetraploidy and, when it arises through hybridization, it is known as allotetraploidy. The evolutionary implications of the two mechanisms are somewhat
different. Autotetraploidy results in an immediate
doubling of homologous gene content, with redundant
genes freed to evolve outside the constraints of natural
selection, although there is no sudden increase in
genetic diversity. Allotetraploidy, in uniting dissimilar
genomes, gives rise to sudden large-scale increase in
genetic diversity, a saltatory effect akin to endosymbiotic union.
Triploidy cannot reduce to haploid eggs or sperm
during meiosis because three cannot divide into two
equal parts. This is why the hybrid of a tetraploid
watermelon crossed with a diploid watermelon results
in a triploid, which is seedless. A putative humanchimpanzee hybrid would also be sterile because the
diploid complement of the great apes, other than the
human, is 2 × 24. This led Muller to state that polyploidy could play little part in animal evolution (Muller,
1925). In fact, triploidy is not an intermediate state in
the formation of even ploidy. It was an unfortunate
consequence of such mistaken early opinion that the
study of polyploidy in plants and animals was biased
for most of the following century (Mable, 2004). Today,
we know that triploids can reproduce through parthenogenesis (e.g. in the whiptail lizard, Cnemidophorus
uniparens). Occasionally, triploids can even reproduce
sexually. The male green toad, Bufo pseudoraddei
baturae, which inhabits an isolated region of the Karakoram mountain range, reduces its sperm to haploid
by premeiotic elimination of one complete set of chromosomes whereas the triploid female creates diploid
ova by premeiotic duplication of one set of chromosomes. Thus fertilization of the diploid egg by the haploid sperm restores the zygote to triploidy (Stöck et al.,
2002). Otto & Whitton (2000) concede that, although
polyploidy is rarer in animals than in plants, there are
now hundreds of examples of recent and ancient polyploidization events even in animals. Even ploidy, in
particular tetraploidy, appears to be the most malleable and constructive mechanism of polyploidy for animal and plant genomes. Moreover, recent genomic
analyses suggest that tetraploidy may have played an
important part in the evolution of vertebrates.
Ohno’s most challenging proposition was that there
had been two rounds of genomic duplication in vertebrate evolution. Today, although his calculations of
gene numbers and his timings of the two duplication
events have required correction, his proposition is
gaining support (Spring, 1997, 2003; Skrabanek &
Wolfe, 1998; Furlong & Holland, 2004).
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GENOMIC CREATIVITY AND NATURAL SELECTION
Hox genes possess a conserved 183 nucleotide
sequence, known as the homeobox sequence, which
encodes a conserved DNA binding structure, the
homeodomain (Gehring, 1998; Martinez & Amemiya,
2002). These are ancient in their evolution and,
although body plans change from phylum to phylum,
the genes themselves show remarkable conservation.
Where humans have four clusters of homeobox genes,
invertebrates, such as insects and sea urchins, and
more importantly still, primitive chordates such as
Amphioxus, have only one. Sequencing suggests that
the four homeobox clusters found in humans must
have arisen by duplication of an ancestral single cluster (Schughart, Kappen & Ruddle, 1989; Finnerty &
Martindale, 1998; De Rosa, 1999). Holland and colleagues have demonstrated similar four-fold increases
between Amphioxus and humans in two other developmental clusters, a parahox cluster containing three
genes (Brooke, Garcia-Fernandez & Holland, 1998;
Pollard et al. 2000) and the NK homeobox genes (Luke
et al., 2003). This is further supported by the discovery
of sets of similar genes found scattered throughout the
human chromosomes, a finding confirmed by other
studies in which duplicated genes were found to litter
the human genome (Lundin, 1993; Pebusque et al.,
1998; Furlong & Holland, 2004). In a further systematic and objective analysis of Ohno’s theory, Ken Wolfe
and colleagues at Trinity College, Dublin, analysed
the human genome to identify far more such paralogous chromosomal regions that could be explained
by alternative mechanisms (McLysaght, Hokamp &
Wolfe, 2002), concluding that there had to be a minimum of one round of whole genome duplication leading to polyploidy in human evolution. Furlong &
Holland (2004), although cautious in drawing conclusions from homeobox gene duplication alone, admit
that, in reviewing the phylogenetic information available from a wider screening of Amphioxus and vertebrate genes, Ohno was probably right in his contention
of two whole genome duplications in the vertebrate
lineage: the first corresponding to the origins of the
cephalochordates and hagfish (c. 510 Mya) and the
second perhaps between the lamprey and origins of
cartilaginous fish (c. 420 Mya). This theory has been
labelled the 2R hypothesis, while some authors have
proposed increasing it to 3R or even 4R, but with these
additional duplications confined to teleost fish (Meyer
& Schartl, 1999; Málaga-Trillo & Meyer, 2001; Meyer
& Van de Peer, 2003).
An alternative hypothesis has been advanced to
explain these findings: adaptive assembly through a
combination of tandem duplication and adaptive shuffling (Hughes, 1998; Furlong & Holland, 2004). Possibly a combination of whole genome duplications and a
series of adaptive assemblies may have contributed.
Meanwhile, authorities differ on the likely mechanism
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of the whole genome duplications. Where Meyer looks
to autotetraploidy, he admits that after such a great
period of time and genetic change ‘it is impossible to
differentiate between the two alternatives’ (personal
communication). Wolfe on the other hand agrees with
Spring that it is most likely to have arisen through
allotetraploidy (Spring, 1997; A. P. Wolfe: pers.
comm.). If this interpretation is correct, there were
two key saltations in vertebrate evolution, arising
from sexual crossing between different species.
HYBRIDIZATION
Darwin devoted a chapter to hybridization in The
Origin, but, viewing speciation as strictly divergent,
he failed to develop the idea of reticulate evolution.
During the 1930s, Dobzhansky and Mayr further
dismissed hybridization as maladaptive, no more than
a tool for understanding the process of speciation
(Arnold, 1997: 7; Mable, 2004). They went further, pioneering the ‘Biological Species Concept’ (BSC), which
sees reproductive barriers to cross-species breeding as
an integral component of ‘speciation’. Muller predicted
the same for dioecious plants. However, some botanists resisted this and Lotsy, for example, insisted that
hybridization was a primary mechanism for evolutionary change (Lotsy, 1916). Such was the prejudice
against hybrids among zoologists, it led to the notorious hybrid policy of the US Endangered Species act of
1973, which deemed hybrids unworthy of conservation, a policy that had to be rescinded in 1990 (Mallet,
2005). In recent decades, a growing number of biologists have come to interpret the BSC is a general
guide, and not an immutable law. Advances in genetic
mapping have revealed several pathways by which
plant hybrid lineages can be stabilized, including apomixis (asexual reproduction via seed), allopolyploidy,
and homoploid speciation (Rieseberg & Noyes, 1998;
Buerkle et al., 2000). Two species of sunflower, Helianthus annuus and Helianthus petiolaris, are endemic to
central and western USA while three species, Helianthus anomalus, Helianthus deserticola and Helianthus paradoxus, grow in extreme environments such
as the dry, sandy soils of Nevada and Utah, or the salt
marshes of West Texas. Rieseberg and colleagues at
Indiana University have shown that whereas
H. annuus and H. petiolaris are diploid, those species
surviving the extreme environments are homoploid
hybrids of the two other species, dating back to interspecies unions between 60 000 and 200 000 years ago
(Rieseberg et al., 2003). The hybrids displayed a survival advantage through a variety of mechanisms,
including increased leaf succulence and a better ability to extrude mineral ions. Rieseberg et al. (2003)
expresses the opinion that hybridization provides a
‘largely unexplored mechanism for large and rapid
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F. P. RYAN
adaptive transitions, such as the colonization of
discrete and divergent ecological niches . . . because,
unlike mutation, it provides genetic variation at hundreds or thousands of genes in a single generation’.
Rieseberg & Noyes (1998) concluded that allopolyploidy is the most frequent solution to the problems of
hybrid sterility and segregation, with genome duplication leading to the formation of meiotically normal
and gametically fertile allopolyploids. Moreover,
genome duplication also leads to instantaneous reproductive isolation between the new allopolyploid offspring and its parental species. Mapping data
indicates that the situation is even more complex
when the polyploid hybrids are derived from more
closely related genomes. And it is different again
where the hybrid embodies homoploid recombination
of the haploid gametes, in which case deterministic
natural selection for the most fertile or viable hybrid
segregants, rapid chromosomal evolution, and the
availability of habitats suitable for the establishment
of hybrid neospecies all appear to play a critical role.
Many dioecious plants, including the crops of wheat,
maize, sugar cane, coffee, cotton, and tobacco are polyploid, whether through human or natural crossing.
Recent estimates suggest that 70% of angiosperms
have gone through one or more cycles of chromosome
doubling and the frequency of polyploidy in pteridophytes could be as high as 95% (Soltis & Soltis, 1999).
There has been a significant renaissance of interest in
polyploidy over the last decade and this has helped
redefine crucial evolutionary aspects. Where in the
past biologists had assumed that most polyploid species of plant were of a single origin, recurrent origins
are now seen to be the rule, disabusing the notion that
such events were mere happenstance. Over a 50-year
period of observation in a region of eastern Washington and adjacent Idaho, two allotetraploid species of
goatsbeard, Tragonopagon mirus and Tragonopagon
miscellus, may have formed, respectively, 12 and 20
times (Soltis & Soltis, 1999). Rather than a single
polyploidy event leading to a genetically uniform tetraploid species, the new perception is of multiple polyploidies involving different parental genotypes and
resulting in a diverse array of polyploid genotypes.
Subsequent hybridization between these polyploid
genotypes adds even further to genetic variety. In consequence, Soltis & Soltis (1999) suggest that rather
than thinking of plants in terms of origin of ‘species’ it
might be more appropriate to think of them as the origins of ‘recognized species’. Other workers, such as
Martinson et al. (2001), have confirmed Rieseberg’s
contention that hybridization in plants, rather than
being ‘a negative factor as is commonly argued’ may
provide important genetic variation with both ecological and evolutionary significance. Similar potential
evolutionary benefit has also been shown in hybrid
yeasts (Masneuf et al., 1998; Groth, Handen & Piskur,
1999; Marinoni et al., 1999). Moreover, although less
ubiquitous than in plants, hybridization is being
increasingly recognized as an important source of evolutionary novelty in animals.
HYBRIDIZATION IN ANIMALS
In 1925, when Muller drew conclusions from sexual
determination in Drosophila, he assumed that the
Drosophila model extended to most animals. Today, we
know that the Drosophila system of sex determination
is the exception even among dipterans (Sturtevant,
1965). Orr (1990) argued that the rarity of polyploidy
in animals was due to disruption of the dosage compensation mechanism necessary to maintain genetic
balance between males and females for genes found on
the fully functional sex chromosome. Such unbalance
was assumed to be lethal. However, Mable accepts
that, where this might apply in groups such as mammals, the Muller argument no longer explains the
scarcity of polyploidy in all animals (Mable, 2004).
Most animals do not reproduce through heterogamy,
but employ a range of different sex determination systems. In many taxa, the sex of an individual is determined after fertilization by environmental influences,
such as temperature, population density, environmental chemicals, and other cues. For Raff, the differences
between the mechanisms of sex determination of flies,
nematodes, and vertebrates is such as to ‘present a
gulf almost as profound as that separating their body
plans (Raff, 1996: 375). Rather than extrapolating
from Drosophila and mammals, where polyploidy is
admittedly rare, Mable suggests that we widen our
horizons to ask two pertinent questions. Why is polyploidy more common in some animal groups than in
others? What features do these taxa share with plants
that promote evolution through polyploidization?
Fish are the most diverse vertebrate group, with an
estimated 24 618 species. Many marine species,
including fish, exhibit external fertilization, which
often involves broadcast spawning. Like the pollination strategies of plants, this may facilitate evolution
through hybridization. In 1955, C. L. Hubbs documented over 130 instances of interspecies hybridization in fish, more so in fresh water than salt water
species, and particularly where a large population of
one species was living in close proximity to a much
smaller population of another species (Hubbs, 1955).
More recently, numerous examples of polyploidy and
hybridization across the cladogram of higher fishes
were confirmed by Le Comber & Smith (2004), who
noted that polyploid orders are diverse and, as in
plants, that polyploidy has evolved more than once in
the same taxa. Observing significant phenotypic and
life cycle effects of polyploidy, such as increased body
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GENOMIC CREATIVITY AND NATURAL SELECTION
size, faster growth rate, longer life, and greater ecological stability, they concluded that polyploidy may be
a more widespread evolutionary phenomenon in fishes
than is usually appreciated, offering important potential for speciation. One advantage of hybrid vigour is
the potential for increased resistance to a stressful
environment. This was observed in a recent crisis in
Norwegian rivers, where Atlantic salmon were under
threat from lethal infection with the parasitic worm,
Gyrodactylus salaris. Here, trout–salmon hybrids
were more resistant to lethal infection, resulting in an
increase of hybrid populations from less than 1% to
33% (Bazilchuk, 2004).
Reticulate evolution through hybridization has been
reported by Madeleine van Oppen and colleagues in
corals on the Great Barrier Reef (Márquez et al., 2002;
Miller & van Oppen, 2003), where, in a single night,
up to 150 species of the highly cross-fertile genus
Acropora spawn within hours of each other in the
same ecology. High cross-fertilization rates were found
in vivo, and molecular tree topologies confirmed nonmonophyletic patterns that bore little similarity to
cladistic analysis based on skeletal morphology or to
the fossil record, leading them to conclude that hybridization has contributed to the enormous success of the
species (Van Oppen et al., 2001; AIMS, 2003). Hybridization and polyploidy are becoming increasingly recognized in other genera of corals as well as a wide
variety of marine invertebrates (Pfenninger, Reinhardt & Streit, 2002). In an ongoing study of the
genomic consequence of hybridization in marine invertebrates, Raff and colleagues have shown that recombinational crosses between directly and indirectly
developing species of sea urchin have resulted in novel
gene expression (Nielsen et al., 2000) and novel
ontogenetic pathways (Raff et al., 1999), leading to
the creation of new larval morphology. In perhaps
the boldest, and probably the most controversial, of
hybridization theories, the marine biologist, Donald
Williamson, has studied interphyletic hybridization of
marine invertebrates to advance the theory that
marine larval forms have been transferred between
taxa through a wide variety of hybridizations
(Williamson, 2003).
Recently Mallet (2005) has reviewed the comparative data on hybridization in animals, noting that rarity on a per individual basis is not typified by rarity on
a per species basis. Indeed, fast-track speciation
through homoploid hybridization has recently been
confirmed in Helioconius butterflies, with reproductive isolation deriving from novel wing coloration patterns (Mavárez et al., 2006). He also disagrees with
Mayr’s contention that hybridization in animals
almost never results in gene flow and introgression.
Other authors have reported hybridization in a wide
variety of animal taxa, including insects (Bilton,
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Goode & Mallet, 1999; Harini & Ranamachandra,
2003; Schwartz et al., 2005), birds, including Darwin’s
finches (Grant & Grant, 1992, 1994), and amphibians.
Rana esculenta, a hybrid of Rana lessonae and Rana
ridibunda, has been so successful that it occupies
large parts of the ecology of the parental species (Hotz
et al., 1998). Autopolyploidy and alloploidy are also
common in amphibians, facilitated by the fact that the
sex chromosomes are in an initial state of differentiation (Bogart, 1980; Kobel, 1985; Beçak & Kobashi,
2004). Indeed, as Mable (2004) reports, there appears
to be such flexibility in sex determination in amphibians that it could allow polyploidy without sex disruption. For example, in Rana rugosa, variation in sexdetermining mechanisms has been reported in a
single species (Nishioka & Hannada, 1994), with
some populations showing male heterogamy and
some showing female heterogamy while others switch
to environmentally determined sex under certain
conditions.
Among the mammals, hybrids are not uncommon
between closely related species. For example, the Scottish red deer, Cervus elaphus, has been shown to
hybridize with the Japanese sika deer, Cervus nippon
(Goodman et al., 1999). The hybrid offspring were
found to be normally fertile and there was no evidence
for selection against introgression either way. Hybridization has also been demonstrated between grey
wolves and coyotes (producing ‘red wolves’), among
marsupials such as rock wallabies (O’Neill et al., 1998;
O’Neill et al., 2001), and among the great cats (e.g.
producing subspecies of panther). There is also an
extensive literature on hybrids in nonhuman primates
(Laas, 2001). As whole genomes are sequenced, the
complex nature of evolution, involving different mechanisms of genomic creativity, is increasingly evident.
One such example is the putative endosymbiotic bacterial origin of a cellulose synthesis gene that may
have contributed to the evolution of the fibrous tunic
of ascidians (Dehal et al., 2002). If Patterson and colleagues are correct in their interpretation of comparative sequencing of the chimpanzee and human
genomes, homoploid hybridisation took place between
apes and humans over the first million years or so
after their initial divergence, contributing to the evolution of the human chromosome X (Patterson et al.,
2006).
Recently, Gallardo and colleagues reported the
discovery of the first tetraploid mammal, a desertdwelling red viscacha rat, Tympanoctomys barrerae
(Gallardo et al., 1999). This species has the largest
chromosome complement of any mammal (4n = 102)
and belongs to a monotypic clade of South American
rodents that includes Octomys mimax. The hybridization event that led to T. barrerae is estimated to have
occurred approximately 6.5 Mya (Gallardo & Kirsch,
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2001; Gallardo et al., 2004), suggesting stability over
time for the hybrid genome. Gallardo and colleagues
have also confirmed that another recently described
desert rodent species, Pipanacoctomys aureus (Mares
et al., 2000) is a closely related tetraploid species, with
92 chromosomes. The two allotetraploid species have
evolved an ingenious heterogametic solution to meiosis. T. barrerae sperm contains 51 bivalent chromosomes which behave like diploids in a process known
as ‘diploidization’. This is made possible because the
male possesses three X and one Y chromosomes, with
one of the X chromosomes showing distal end-to-end
bivalency with the Y chromosome. Meiosis in the
male P. aureus also involves diploidization, with 46
bivalents, while females possess four X chromosomes.
The evolution of a stable sex ratio in newly formed
allotetraploid animals with a dominant Y-mechanism
is discussed by Otto & Whitton (2000), and this exposition is congruous with Gallardo’s findings.
Adding such examples to the growing evidence of a
putative hybrid origin of the recurrent genomic duplication in vertebrates, it appears likely that hybridization has played, and is still playing, a major role in the
evolution of plants and an important, if lesser role, in
the evolution of animals. Frequency of hybridization
vs. mutation as a source of novelty is meaningless
because a single recombinational or allopolyploidy
event may have major evolutionary significance, as
seen in the 2R hypothesis and in the studies of Rieseberg and Raff. It remains to be seen whether hybrid
speciation in animals is punctuated, much as Rieseberg & Noyes (1998) concluded from their study of
plants, with long periods of hybrid-zone stasis followed by abrupt transitions in which parental species
are displaced by hybrid neospecies. Other studies
have highlighted the extensive scale and rapidity
of genomic reorganization following polyploidization,
including a number of important non-Mendelian
(epigenetic) phenomena, some of which come into
operation immediately while others manifest more
gradually over an evolutionary time scale (Liu & Wendel, 2002, 2003). Although knowledge is still scarce, it
would appear that retrotransposons may play an
important role in such genomic rationalization (Soltis
& Soltis, 1999; Matzke et al., 2004; Melayah et al.,
2004), although this is neither essential not inevitable
(Baumel et al., 2002). Such endogenous retroviral
elements have been implicated in a ‘diverse array of
evolutionary phenomena’, including genomic restructuring, insertion mutagenesis, the conferring of tissuespecific or developmental regulatory changes, and
epigenetic effects, generating novel genotypes that can
rapidly lead to the origin of new species (Soltis &
Soltis, 2000; Liu & Wendel, 2002). Indeed, epigenetic
novelty is increasingly seen as an important mechanism of evolution in its own right.
EPIGENETICS
Epigenetics has been defined as the study of heritable
changes in gene expression that occur without a
change in DNA sequence (Wolffe & Matzke, 1999; Wu
& Morris, 2001). The term and concept was first
defined by the developmental biologist, Conrad H.
Waddington (Van Speybroeck, 2002), and epigenetics
is currently undergoing a major expansion that comprises a hierarchy of contexts at the intracellular,
intercellular, and organismic level, including the
structural organization and evolution of the genome
(Van Speybroeck, 2000; Van de Vijver, Van Speybroeck
& De Waele, 2002). Cellular (and thus tissue and
organ) differentiation in complex life forms depends
on the stable repression of unwanted genes. This is
largely controlled by epigenetic mechanisms that are
transmitted to future generations by means of ‘epigenetic inheritance systems’ (EIS) (Jablonka & Lamb,
2005). The same authors specify four types of EIS that
play a role in what has been termed ‘cell memory’.
These include ‘steady-state systems’, where a gene,
after being turned on (e.g. by some external or internal
cue), transcribes a product that, through a selfsustaining feedback loop, maintains the activity of
that gene. Descendents of the cell with the specified
gene will inherit this activity, even if the original cue
for gene activation is no longer operative. Most selfsustaining loops are complex, involving several genes,
regulatory regions, and proteins. Interestingly, the
more complex loops are more likely to be stable.
‘Structural inheritance’, as seen in the architectural
memories of ciliates such as Paramecium, was first
described by Beisson & Sonneborn et al. (1965). The
subject has been developed by others, notably
Cavalier-Smith (2004), who has extended it to the selfperpetuating cell membranes and the endoplasmic
reticulum, which he refers to as the ‘membranosome’.
Prions are a very topical example of structurally
inherited entities of considerable importance both theoretically and in medicine.
Jablonka and Lamb’s third epigenetic inheritance
system is through ‘chromatin marking’. Chromatin is
an umbrella term for the DNA, RNA, proteins such as
histones, and other molecules that together constitute
the structure of chromosomes. The same DNA
sequence can be packaged differently in different cell
types, which in turn may determine how accessible it
is for transcription. Certain non-DNA features of chromatin, known as ‘chromatin marks’, may influence
transcription while also being inherited by future generations. The most familiar of these is methylation of
cytosine, which, if densely present in a gene, may prevent transcription. Because chromatin marks may be
affected by environmental factors, Jablonka and Lamb
see in this a potential mechanism for the inheritance
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GENOMIC CREATIVITY AND NATURAL SELECTION
of acquired characteristics; in other words, a neoLamarckian pattern of inheritance (Jablonka & Lamb,
1995). Other chromatin marks include alterations in
the protein complexes that bind to DNA (e.g. gene
expression can be effected through acetylation on the
K9 and K4 lysines of the N-terminal tails of the histones). For some biologists, these suggest a ‘histone
code’ for gene expression and suppression. In many
cases, more than one form of chromatin mark is operational and, indeed, they may influence each other.
Their fourth and final form of epigenetic inheritance
system is through ‘regulatory RNAs’, the best known
of which is RNA interference, or RNAi. First reported
in the late 1990s, these short-chain double-stranded
RNA molecules silence gene expression by binding to
complementary messenger RNAs, when they either
trigger mRNA elimination or they arrest mRNA
translation to protein (Henikoff, 2002; Downard,
2004). Once again, this mechanism may interact with
another; for example, RNAi has been shown to direct
DNA methylation in plants (Mette et al., 2000). To
Jablonka and Lamb’s four EIS systems, I would add a
fifth: ‘paramutation’. In paramutation, two alleles of a
gene interact so that one of the alleles is epigenetically
silenced, and this silenced state, which may involve
increased cytosine methylation, is genetically transmissible (Walker, 1998).
Although it is obvious that epigenetic inheritances
systems were essential for the evolution of complex
organisms, with their differentiated cells, tissues, and
organs, this was thought to be restricted to inheritance through mitosis across cell lineages. However, in
a form known as ‘genomic imprinting’, epigenetic
information had long been seen to be inherited.
Genomic imprinting probably takes place during
gametogenesis but only manifests when both maternal and paternal alleles are present after fertilization,
when only one allele will be expressed whereas the
other remains inactive. In fact, the optimum method
of imprinting is through methylation, which is carried
out by the enzyme DNA methyltransferase in mammals (Delaval & Feil, 2004). Despite awareness of
methylation, it remained problematic, and controversial, to imagine that epigenetic alteration in the germ
line could be a significant mechanism of evolutionary
novelty that was transmitted through meiosis to new
generations. Such views are changing, with epigenetic
inheritance increasingly being demonstrated as a
source of evolutionary novelty in fungi, plants, and
mammals (Roemer et al., 1997; Walker, 1998; Morgan
et al., 1999; Martienssen & Colot, 2001; Stam et al.,
2002; Rakyan et al., 2003; Anway et al., 2005).
Imprinting has also been demonstrated to have a
role in normal human development (Weksberg et al.,
2003) and alteration in epigenetic controls has been
shown to play an important role in human diseases,
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including diabetes, infertility, mental illness, cardiovascular disease, hereditary abnormalities, and
cancers, as well as providing biomarkers for early
diagnosis and prevention (Wolffe & Matzke, 1999;
Walter & Paulsen, 2003; Bjornsson, Fallin & Feinberg,
2004; Feinberg & Tycko, 2004; Klein, 2005). Genomic
imprinting is now a core part of any genetics curriculum and is becoming increasingly familiar to clinicians
(Clayton-Smith, 2003). Meanwhile, the emerging field
of epigenetics is changing views of environmental
influences on health, so much so that, in 2004, the US
National Institutes of Health has funded the first
centre for the comprehensive study of epigenetics and
disease at the Johns Hopkins Medical School in
Baltimore.
EVOLUTIONARY DEVELOPMENT
Evolutionary development, or EvoDevo, is purportedly
the youngest of the evolutionary disciplines having
been granted its own division in the Society for Integrative and Comparative Biology as recently as 1999
(Goodman & Coughlin, 2000). Brian Hall, Professor of
Biology at the University of West Australia in Perth,
has defined it as the study of how development
impinges on evolution and how development itself has
evolved (Hall, 1992). In a recent review of how this
works, Carroll (2005a) acknowledges the early contributions to evolutionary development made by King &
Wilson (1975), Britten, Davidson, and Jacob (Britten
& Davidson, 1969, 1971; Jacob, 1977). He also notes
that two-thirds of the sequences exposed to selection
in the human genome are noncoding, in the sense they
do not translate to proteins (Waterston et al., 2002).
This, he cautions, might lead to unrealistic expectations about what can be learned from comparisons of
genome sequences alone. Raff looks back on much of
the evolutionary preoccupations of the past as being
overly concerned with what he terms ‘microevolution’
as seen in laboratory populations and in the wild,
‘including mutation, the nitty-gritty of gene flow
between populations, the close work of selection and
speciation itself ’ (Raff, 1996: 30). Davidson (2001: 19)
emphasizes much the same point in stating that ‘classical Darwinian evolution could not have provided an
explanation, in a mechanistically relevant way, of how
the diverse forms of animal life actually arose during
evolution, because it matured before molecular biology
provided explanations of the developmental process’.
Both Raff and Davidson look to changes in gene regulatory networks as the primary study of evolutionary
development because therein lies the key to evolution
of body form. Carroll, while acknowledging that
changes to both regulatory sequences and translational sequences can and do contribute to the evolution of form, also concludes that, although the
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evidence base is still modest, there is adequate basis,
both empirical, and theoretical, to conclude that evolution of morphological anatomy occurs primarily
through changes in regulatory sequences (Carroll,
1995: 1164).
Evolutionary geneticists have long been familiar
with developmental evolution in the form of heterochronic and heterotopic mutations (De Beer, 1958),
which affect developmental timing and spatial situation. These concepts and their histories are defined
and explained by Raff (1996: 258), who emphasizes
that heterotopy is only recently coming under detailed
molecular scrutiny while the many evolutionary
assumptions attributed to heterochronies are the
results of the various processes outlined above, which
are hardly exclusively mutational and are not in
themselves related to developmental timing. We have
touched upon examples of heterotopy in Drosophila
and an interesting example of heterochrony is suggested by Truman & Riddiford (1999) in their novel
hypothesis for the origins of the insect larva and pupa.
Paedogenesis is another example of evolution through
heterochrony, in which a persisting larval form may
give rise to a new evolutionary taxon. It is often misquoted as ‘neoteny’, a condition in which larval characters are retained for prolonged periods of the life
cycle, but in which larvae do not reproduce (Garstang,
1929). Smith extends such preoccupations to the need
to consider sequence heterochrony as well as focusing
on changes in size and shape (Smith, 2002). Clearly, if
we are to understand the contribution of evolutionary
development, then we need to understand key
features of the regulatory apparatus (Carroll, 1995:
1161−1162). Inevitably this is complex.
Individual regulatory proteins function in many different contexts, where the function of the same protein
may be context dependent, with different genetic
targets. Meanwhile, the tissue-specific and temporal
control of gene expression, encoding these regulatory
proteins, is itself typically governed by arrays of regulatory elements embedded in regions that flank the
coding regions and that lie in introns. More than 20%
of human genes, and a much larger percentage of
plant genes, belong to families that are the products of
duplication and divergence. The same gene can, as we
have already seen, encode different proteins. Although
Carroll writes exclusively in terms of mutations, it is
obvious that many, if not all, of the above mechanisms
could alter the coding or expression of a regulatory
protein, and thus in turn potentially affect many pathways. Extrapolating from the literature of mutation, a
single evolutionary novelty affecting multiple pathways, expressing multiple phenotypic traits, will
result in ‘pleiotropic’ change.
Developmental biologists, such as Raff and Davidson, emphasize the role of form in the origins of major
taxa rather than the less dramatic physiological and
minor anatomical changes that commonly lead to speciation within genera. The distinction may sometimes
seem a little artificial. For example, the endosymbiotic
incorporation of mitochondria and chloroplasts did not
immediately give rise to a change in form, yet the
ultimate implications for the developmental form in
a wide diversity of animals and plants were farreaching. In a more speculative sense, if Williamson is
right in theorizing that hybridization across widely
separated taxa may have played a major role in
the Cambrian explosion (Williamson 2006) and if
Villarreal is right in associating the origins of the vertebrates with an explosion in the symbiogenetic interactions of endogenous retroviruses (Villarreal, 2005),
developmental biologists need to consider all modalities for change.
Evolutionary development is a relatively young discipline and much remains to be investigated in the
future. Carroll (1995; 2005b), acknowledges this while
summarizing the growing evidence for the association
between changes in homeotic gene number, regulation
or function, and the evolution of morphological traits
in arthropods, plants, and vertebrates. Davidson looks
to an increasing understanding from the cooption of
regulatory genes to new pattern formation, illustrating this with examples from the very different adult
body plans of the deuterostomes, which have evolved
from relatively conserved regulatory systems despite
their monophyletic origin, and he extrapolates this to
hox cluster patterning and evolutionary changes in
hox gene expression in the arthropods and other taxa
(Davidson, 2001: final chapter). Raff discusses a number of topics that are likely to be involved in future
investigations, including developmental constraints,
modularity, dissociation, and co-option. He agrees
with the over-riding precept of this review that
‘internal rules should not be expected to supersede
Darwinian selection, but rather to complement it’.
Meanwhile, the advance of molecular and developmental studies is pioneering a new overview of
‘macroevolution’ in which it is anticipated that evolutionary development will shed a clearer light on many
as-yet poorly explained areas.
OTHER GENOMIC MECHANISMS
This review does not aspire to be fully comprehensive
of genomic creativity, although I hope to have included
most major categories. One important source that has
not been covered is horizontal gene transfer in microbial evolution, which has a potential so great that
Sorin Sonea suggested that all the strains of bacteria
in the world form a single pool in which ‘temporary,
adaptable symbioses’ that solve problems of survival
are the way of life (Sonea, 1991; Sonea & Mathieu,
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
GENOMIC CREATIVITY AND NATURAL SELECTION
2000). Other examples of horizontal gene transfer in
prokaryotes and eukaryotes are provided by Syvanen
& Kado (1998).
CONCLUSION
We can no longer assume that mutation is the exclusive source of hereditary change any more than we can
assume that genomes are static collections of genes
and DNA. Rather, as in the words of Zhou & Mishra
(2003), ‘present genomes can be viewed as a snapshot
of an ongoing genomic evolutionary process.’ In an earlier publication (Ryan, 2002/2003), I coined the term
‘genomic creativity’ to encompass the multifaceted
source of evolutionary variation. If this umbrella concept is to be useful, I also need to define the genome,
which, for these purposes, is the sum of the various
hereditary components of biodiversity, including the
genetic and translational machinery of the nucleus
and cytoplasm, together with the epigenetic apparatus
for change. Viruses should be treated as living, at the
very least for evolutionary purposes (Ryan, 2002/2003;
Mindell & Villarreal, 2003; Villarreal, 2004). Moreover, in what is essentially an overview of one limb in
a two-limbed process, one should acknowledge the
importance of that second limb, namely the application of selection not only at all levels of the genome,
but also at all levels of phenotypic variation, with the
inevitable extrapolation to population and ecology.
REFERENCES
Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne
JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA,
Galle RF et al. 2000. The genome sequence of Drosophila
melanogaster. Science 287: 2185–2195.
AIMS Research. 2003. Evolutionary hope. Feature published
on line, 29 April. Available at http://www.aims.gov.au/pages/
about/communications/backgrounders/20030429-evolutionaryhope.html
Andersson A-C, Merza M, Venables P, Pontén F,
Sundström J, Cohen M, Larsson E. 1996. Elevated levels
of the endogenous retrovirus ERV3 in human sebaceous
glands. Journal of Investigative Dermatology 106: 125–128.
Andersson GE, Zomorodipour A, Andersson JO,
Sicheritz-Pontén T, Alsmark CE, Podowski RM,
Näslund AK, Eriksson A-S, Winkler HH, Kurland CG.
1998. The genome sequence of Rickettsia prowazeki and the
origin of mitochondria. Nature 396: 133–140.
Andersson A-C, Venables PJW, Tonjes RR, Scherer J,
Eriksson L, Larsson E. 2002. Developmental expression of
HERV-R (ERV-3) and HERV-K in human tissue. Virology
297: 220–225.
Anway MD, Cupp AS, Uzumcu M, Skinner MK. 2005. Epigenetic transgenerational actions of endocrine disruptors
and male fertility. Science 308: 1466–1469.
667
Arnold ML. 1997. Natural hybridisation and evolution.
Oxford: Oxford University Press.
Bannert N, Kurth R. 2004. Retroelements and the human
genome: new perspectives on an old relation. Proceedings of
the National Academy of Sciences of the United States of
America 101: 14572–14579.
Barbulescu M, Turner G, Seaman MI, Deinard AS, Kidd
KK, Lenz J. 1999. Many human endogenous retroviruses K
(HERV-K) proviruses are unique to humans. Current Biology
9: 861–868.
Baumel A, Ainouche M, Kulender R, Schulman AH. 2002.
Retrotransposons and genomic stability in populations of the
young allopolyploid species Spartina anglia C.E. Hubbard
(Poaceae). Molecular Biology and Evolution 19: 1218–1227.
Bazilchuk N. 2004. Salmon crisis in Norway. New Scientist,
28 February, 14.
Beçak ML, Kobashi LS. 2004. Evolution by polyploidy and
gene regulation in Anura. Genetics and Molecular Research
3: 195–212.
Beisson J, Sonneborn TM. 1965. Cytoplasmic inheritance of
the organization of the cell cortex in Paramecium aurelia.
Proceedings of the National Academy of Sciences of the
United States of America 53: 275–282.
Bell PJL. 2001. Viral eukaryogenesis: was the ancestor of the
nucleus a complex DNA virus? Journal of Molecular Evolution 53: 251–256.
Belle E, Beckage NE, Rousselet J, Poirié M, Lemeunier
F, Drezen J-M. 2002. Visualization of polydnavirus
sequences in a parasitoid wasp chromosome. Journal of
Virology 76: 5793–5796.
Bermudes D, Margulis L. 1987. Symbiont acquisition as
neoseme: Origin of species and higher taxa. Symbiosis 4:
185–198.
Bhattacharya D, Friedl T, Damberger S. 1996. Nuclearencoded rDNA group I introns: origin and phylogenetic
relationships of insertion site lineages in the green algae.
Molecular Biology and Evolution 13: 978–989.
Bilton DT, Goode D, Mallet J. 1999. Genetic differentiation
and natural hybridisation between two morphological forms
of the common woodlouse, Oniscus asellus Linnaeus 1758.
Heredity 82: 462–469.
Bjornsson H, Fallin D, Feinberg AP. 2004. An integrated
epigenetic and genetic approach to common human disease.
Trends in Genetics 20: 350–358.
Blaise S, de Parseval N, Bénit L, Heidmann T. 2003.
Genomewide screening for fusogenic human endogenous
retrovirus envelopes identifies syncytin 2, a gene conserved
on primate evolution. Proceedings of the National Academy
of Sciences of the United States of America 100: 13013–
13018.
Blond J-L, Lavillette D, Cheynet V, Bouton O, Oriol G,
Chapel-Fernandes S, Mandrand B, Mallet F, Cosset
F-L. 2000. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta
and fuses cells expressing the type D mammalian retrovirus
receptor. Journal of Virology 74: 3321–3329.
Bogart JP. 1980. Evolutionary implications of polyploidy in
amphibians and reptiles. In: Lewis WH, ed. Polyploidy:
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
668
F. P. RYAN
biological relevance. New York, NY: Plenum Press, 341–
378.
Bonnaud B, Bouton O, Oriol G, Cheynet V, Duret L,
Mallet F. 2004. Evidence of selection on the domesticated
ERVWE1 env retroviral element involved in placentation.
Molecular Biology and Evolution 21: 1895–1901.
Bowler PJ. 1992. The eclipse of Darwinism. Baltimore, MD:
The Johns Hopkins University Press.
Britten RJ. 1996. DNA sequence insertion and evolutionary
variation in gene regulation. Proceedings of the National
Academy of Sciences of the United States of America 93:
9374–9377.
Britten RJ, Davidson EH. 1969. Gene regulation for higher
cells: a theory. Science 165: 349–357.
Britten RJ, Davidson EH. 1971. Repetitive and nonrepetitive DNA sequences and a speculation on the origins of
evolutionary novelty. Quarterly Review of Biology 46: 111–
138.
Brooke NM, Garcia-Fernandez J, Holland PWH. 1998.
The ParaHox gene cluster is an evolutionary sister of the
Hox gene cluster. Nature 392: 920–922.
Buerkle CA, Morris RJ, Asmussen MA, Rieseberg LH.
2000. The likelihood of homoploid hybrid speciation. Heredity 4: 441–451.
Cameron RA, Mahairas G, Rast JP, Martinez P, Biondi
TR, Swartzell S, Wallace JC, Poustka AJ, Livingston
BT, Wray GA, Ettensohn CA, Lehrach H, Britten RJ,
Davidson EH, Hood L. 2000. A sea urchin genome project:
sequence scan, virtual map, and additional resources. Proceedings of the National Academy of Sciences of the United
States of America 97: 9514–9518.
Carroll SB. 1995. Homeotic genes and the evolution of arthropods and chordates. Nature 376: 479–485.
Carroll SB. 2005a. Evolution at two levels: on genes and form.
PLoS Biology 3: e245.
Carroll SB. 2005b. Endless forms most beautiful: the new science of Evo Devo and the making of the animal kingdom.
New York, NY: W.W. Norton Co.
Cavalier-Smith T. 2004. The membranosome and membrane
heredity in development and evolution. In: Hirt RP, Horner
DS, eds. Organelles, genomes and eukaryote phylogeny: an
evolutionary synthesis in the age of genomics. Boca Raton,
FL: CRC Press.
Chetverikov S. 1926. O nekotorykh momentakh evoliutsionnogo protsessa s tochki zreniia sovremennoi geneteki [On
several aspects of the evolutionary process from the viewpoint of modern genetics]. Zhurnal Eksperimental’noi
Biologii, Series A 2: 3–54.
Clayton-Smith J. 2003. Genomic imprinting as a cause of disease. British Medical Journal 327: 1121–1122.
Croft L, Schandorff S, Clark F, Burrage K, Arctander P,
Mattick J. 2000. ISIS, the intron information system,
reveals the high frequency of alternate splicing in the human
genome. Nature Genetics 24: 340–341.
Darwin C. 1859. The origin of species by means of natural
selection. London: John Murray.
Davidson EH. 2001. Genomic regulatory systems. San Diego,
CA: Academic Press.
Dawkins R. 1976. The selfish gene. Oxford: Oxford University
Press.
De Beer G. 1958. Embryos and ancestors. Oxford: Oxford University Press.
De Groot N, Otting N, Doxiadis GGM, BallaJhagjhoorsingh SS, Heeney JL, van Rood JJ, Gagneux
P, Bontrop RE. 2002. Evidence for an ancient selective
sweep in the MHC class I gene repertoire of chimpanzees.
Proceedings of the National Academy of Sciences of the
United States of America 99: 11748–11753.
De Rosa, Grenier JK, Andreeva T, Cook CE, Adoutte A,
Akam M, Carroll SB, Balavoine G. 1999. Hox genes in
brachiopods and priapulids and protostome evolution.
Nature 399: 772–776.
De Vries H. 1906. Species and varieties, their origin by mutation. Chicago, IL: Open Court.
Dehal P, Satou Y, Campbell RK, Chapman J, Degnan B,
De Tomaso A, Davidson B, Di Gregorio A, Gelpke M,
Goodstein DM et al. 2002. The draft genome of Ciona
intestinalis: insights into chordate and vertebrate origins.
Science 298: 2157–2167.
Delaval K, Feil R. 2004. Epigenetic regulation of mammalian
genomic imprinting. Current Opinion in Genetics and Development 14: 188–195.
Dobzhansky T. 1937. Genetics and the origin of species. New
York, NY: Columbia University Press.
Downard J. 2004. Science, medicine and the future: RNA
interference. British Medical Journal 328: 1245–1248.
Dunn CA, Medstrand P, Mager DL. 2003. An endogenous
retroviral long terminal repeat is the dominant promoter for
human β1,3-galactosyltransferase 5 in the colon. Proceedings of the National Academy of Sciences of the United States
of America 100: 12841–12846.
Endler JA, McLellan T. 1988. The processes of evolution:
towards a newer synthesis. Annual Review of Ecology and
Systematics 19: 395–421.
Espagne E, Dupuy C, Huguet E, Cattolico L, Provost B,
Martins N, Poirié M, Periquet G, Drezen JM. 2004.
Genome sequence of a polydnavirus: insights into symbiotic
virus evolution. Science 306: 286–289.
Feinberg AP, Tycko B. 2004. The history of cancer epigenetics. Nature Reviews of Cancer 4: 143–153.
Finnerty JR, Martindale MQ. 1998. The evolution of the
Hox cluster: insights from outgroups. Current Opinions in
Genetics and Development 8: 681–687.
Fisher RA. 1930. The genetical theory of natural selection.
Oxford: Clarendon Press.
Furlong RF, Holland PWH. 2004. Polyploidy in vertebrate
ancestry: Ohno and beyond. Biological Journal of the Linnean Society 82: 425–430.
Gagneux P, Wills C, Gerloff U, Tautz D, Morin PA, Boesch
C, Fruth B, Hohmann G, Ryder OA, Woodruff DS. 1999.
Mitochondrial sequences show diverse evolutionary histories
of African hominoids. Proceedings of the National Academy of
Sciences of the United States of America 96: 5077–5082.
Gallardo MH, Bickham JW, Honeycutt RL, Ojeda RA,
Kohler N. 1999. Discovery of tetraploidy in a mammal.
Nature 401: 341.
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
GENOMIC CREATIVITY AND NATURAL SELECTION
Gallardo MH, Kirsch JWA. 2001. Molecular relationships
among Octodontidae (Mammalia: Rodentia: Caviomorpha).
Journal of Mammalian Evolution 8: 73–89.
Gallardo MH, Kirsch JWA. 2004. Whole-genome duplications in South American desert rodents (Octodontidae). Biological Journal of the Linnean Society 82: 443–451.
Garstang W. 1929. The morphology of the Tunicata, and its
bearings on the phylogeny of the Chordata. Quarterly Journal of Microscopic Science 72: 51–187.
Gehring WJ. 1998. Master control genes in development and
evolution: the homeobox story. New Haven, CT: Yale University Press.
Gilbert W. 1986. The RNA world. Nature 319: 618.
Gilbert SF. 2003. Developmental biology, 7th edn. Sunderland, MA: Sinauer Associates Inc., 130.
Goodman SJ, Barton NH, Swanson G, Abernethy K,
Pemberton JM. 1999. Introgression through rare hybridisation: a genetic study of a hybrid zone between red and sika
deer (Genus Cervus) in Argyll, Scotland. Genetics 152: 355–
371.
Goodman CS, Coughlin BC. 2000. The evolution of evo-devo
biology. Proceedings of the National Academy of Sciences of
the United States of America 97: 4424–4425.
Goodwin B. 1994. How the leopard changed its spots. London:
Weidenfield & Nicholson.
Gould SJ, Eldredge N. 1977. Punctuated equilibria: the
tempo and mode of evolution reconsidered. Paleobiology 3:
115–151.
Grant PR, Grant BR. 1992. Hybridisation in bird species.
Science 256: 193–197.
Grant PR, Grant BR. 1994. Phenotypic and genetic effects of
hybridisation in Darwin’s finches. Evolution 48: 297–316.
Gray MW. 1998. Rickettsia, typhus and the mitochondrial
connection. Nature 396: 109–110.
Groth C, Hansen J, Piskur J. 1999. A natural chimeric yeast
containing genetic material from three species. International
Journal of Systematic Bacteriology 49: 1933–1938.
Haldane JBS. 1932. The causes of evolution. London:
Longmans.
Hall BK. 1992. Evolutionary developmental biology. New York,
NY: Chapman & Hall.
Harini BP, Ramachandra NB. 2003. Evolutionary experimentation through hybridisation under laboratory conditions in Drosophila: evidence for recombinational speciation.
BMC Evolutionary Biology 3: 20.
Hartl DL, Jones EW. 2001. Genetics, analysis of genes and
genomes, 5th edn. Boston, MA: Jones and Bartlett, 728.
Hecht J. 2004. Conference report, Palaeontology: rogue finger
gene got bats airborne. New Scientist, 13 November, 16.
Henikoff S. 2002. Editorial: beyond the central dogma. Bioinformatics 18: 223–225.
Hotz H, Semlitsch RD, Gutmann E, Guex G-D, Beerli P.
1998. Spontaneous heterosis in larval life-history traits of
hemiclonal frog hybrids. Proceedings of the National Academy of Sciences of the United States of America 96: 2171–
2176.
Hubbs CL. 1955. Hybridisation between fish species in
nature. Systematic Zoology 4: 1–20.
669
Hughes AL. 1998. Phylogenetic tests of the hypothesis of block
duplication of homologous genes on human chromosomes 6, 9
and 1. Molecular Biology and Evolution 15: 854–870.
Hughes JF, Coffin JM. 2001. Evidence for genomic rearrangements mediated by human endogenous retroviruses
during primate evolution. Nature Genetics 29: 487–489.
Huxley J. 1942. Evolution: the modern synthesis. London:
Allen & Unwin.
International Human Genome Sequencing Consortium.
2001. Initial sequencing and analysis of the human genome.
Nature 409: 860–921.
Jablonka E, Lamb MJ. 1995. Epigenetic inheritance and evolution: the Lamarckian dimension. Oxford: Oxford University Press.
Jablonka E, Lamb MJ. 2005. Evolution in four dimensions.
Cambridge, MA: MIT Press.
Jacob F. 1977. Evolution and tinkering. Science 196: 1161–
1166.
Jeon KW. 1991. Amoeba and x-bacteria: symbiont acquisition
and possible species change. In: Margulis L, Fester R, ed.
Symbiosis as a source of evolutionary innovation. Cambridge,
MA: MIT Press.
Jeon KW. 2004. Genetic and physiological interactions in the
amoeba-bacteria symbiosis. Journal of Eukaryotic Microbiology 51: 502–508.
Johannsen W. 1911. The genotype conception of heredity.
American Naturalist 45: 129–159.
King MC, Wilson AC. 1975. Evolution at two levels in
humans and chimpanzees. Science 188: 107–116.
Klein G. 2005. Surveillance team against cancer. Nature 434:
150.
Kobel HR. 1985. Sex determination in polyploid Xenopus.
South African Journal of Science 81: 205–206.
Laas BC. 2001. The effects of interbreeding on the morphological and genetic attributes of non-human primates. Online Thesis with detailed discussion and references, http://
www.soa.ilstu.edu/anthropology/theses/laas.
Landthaler M, Begley U, Lau NC, Shub DA. 2002. Two
self-splicing group I introns in the ribonucleotide reductase
large subunit gene of Staphylococcus aureus phage Twort.
Nucleic Acids Research 30: 1935–1943.
Le Comber SC, Smith C. 2004. Polyploidy in fishes: patterns
and processes. Biological Journal of the Linnean Society 82:
431–442.
Lewontin R. 1998. The triple helix. Cambidge, MA: Harvard
University Press.
Liu B, Wendel JF. 2002. Non-Mendelian phenomena in
allopolyploid evolution. Current Genomics 3: 489–505.
Liu B, Wendel JF. 2003. Epigenetic phenomena and the evolution of plant allopolyploids. Molecular Phylogenetics and
Evolution 29: 365–379.
Lotsy JP. 1916. Evolution by means of hybridisation. The
Hague: M. Nijhoff.
Löwer R, Löwer J, Kurth R. 1996. The viruses in all of us:
characteristics and biological significance of human endogenous retrovirus sequences. Proceedings of the National
Academy of Sciences of the United States of America 93:
5177–5184.
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
670
F. P. RYAN
Luke GN, Castro LPC, McLay K, Bird C, Coulson A, Holland PWH. 2003. Dispersal of NK homeobox gene clusters
in amphioxus and humans. Proceedings of the National
Academy of Sciences of the United States of America 100:
5292–5295.
Lundin LG. 1993. Evolution of the vertebrate genome as
reflected in paralogous chromosomal regions in man and the
house mouse. Genomics 16: 1–19.
Mable BK. 2004. ‘Why polyploidy is rarer in animals than in
plants’: myths and mechanisms. Biological Journal of the
Linnean Society 82: 453–466.
Málaga-Trillo E, Meyer A. 2001. Genome duplications and
accelerated evolution of Hox genes and cluster architecture
in teleost fishes. American Zoologist 41: 676–686.
Mallet J. 2005. Hybridization as an invasion of the genome.
Trends in Ecology and Evolution 20: 229–237.
Mares MA, Braun JK, Bárquez RB, Díaz MM. 2000. Two
new genera and species of halophytic desert mammals from
isolated salt flats in Argentina. Occasional Papers of the
Museum of Texas Technical University 203: 1–27.
Margulis L. 1970. Origin of eukaryotic cells. New Haven, CT:
Yale University Press.
Margulis L, Schwartz KV. 1998. Five kingdoms: an illustrated guide to the phyla of life on earth, 3rd edn. New York,
NY: WH Freeman.
Marinoni G, Manuel M, Petersen RF, Hvidtfeldt J, Sulo
P, Pittkur J. 1999. Horizontal transfer of genetic material
among Saccharomyces Yeasts. Journal of Bacteriology 181:
6488–6496.
Márquez LM, van Oppen MJH, Willis BL, Miller DJ. 2002.
Sympatric populations of the highly cross-fertile coral
species Acropora hyacinthus and Acropora cytherea are
genetically distinct. Proceedings of the National Academy of
Sciences of the United States of America 269: 1289–1294.
Martienssen RA, Colot V. 2001. DNA methylation and epigenetic inheritance in plants and filamentous fungi. Science
293: 1070–1074.
Martinez P, Amemiya CT. 2002. Review: genomics of the
Hox gene cluster. Comparative Biochemistry and Physiology,
Part B 133: 571–580.
Martinson GD, Whitham TG, Rurek RJ, Keim P. 2001.
Hybrid populations selectively filter gene introgression
between species. Evolution 55: 1325–1335.
Masneuf I, Hansen J, Groth C, Piskur J, Dubourdieu D.
1998. New hybrids between Saccharamyces sensu stricto
yeast species found among wine and cider production
strains. Applied and Environmental Microbiology 64: 3887–
3892.
Mattick JS. 1994. Introns: evolution and function. Current
Opinion in Genetics and Development 4: 823–831.
Matzke M, Gregor W, Mette MF, Aufsatz W, Kanno T,
Jakowitsch J, Matzke AJM. 2004. Endogenous pararetroviruses of allotetraploid Nicotiana tabacum and its diploid
progenitors, N. sylvestris and N. tomentosiformis. Biological
Journal of the Linnean Society 82: 627–638.
Mavárez J, Salazar CA, Bermingham E, Salcedo C, Jiggins CD. 2006. Speciation by hybridization in Helioconius
butterflies. Nature 441: 868–871.
Maynard Smith J. 1991. A Darwinian view of symbiosis. In:
Margulis L, Fester R, ed. Symbiosis as a source of evolutionary innovation. Cambridge, MA: MIT Press.
Maynard Smith J, Szathmáry E. 1995. The major transitions in evolution. Oxford: Oxford University Press.
Maynard Smith J, Szathmáry E. 1999. The origins of life.
Oxford: Oxford University Press.
Mayr E. 1998. In: Mayr E, Provine WB, eds. The evolutionary
synthesis. Cambridge, MA: Harvard University Press, 20.
McLysaght A, Hokamp K, Wolfe KH. 2002. Extensive
genomic duplication during early chordate evolution. Nature
Genetics 2: 128–129.
Medstrand P, van de Lagemaat LN, Mager DL. 2002. Retroelement distributions in the human genome: variations
associated with age and proximity to genes. Genome
Research 12: 1483–1495.
Melayah D, Lim KY, Bonnivard E, Chalhoub B, De Borne
FD, Mhiri C, Leitch AR, Grandbastien M-A. 2004. Distribution of the YNt1 retrotransposon family in the amphidiploid tobacco (Nicotiana tobacum) and its wild Nicotiana
relatives. Biological Journal of the Linnean Society 82: 639–
649.
Mendel G. 1866. Versuche über pflanzen-hybriden. Verhandlungen Des Naturforschenden Vereines in Brünn 4: 3–47.
Merezhkovskii C. 1910. La plante considérée comme un complexe symbiotique. Bulletin of the de la Société Naturelles 6:
17–98.
Mette MF, Aufsatz W, van der Winden J, Matzke MA,
Matzke AJM. 2000. Transcriptional silencing and promoter
methylation triggered by double-stranded DNA. European
Molecular Biology Organization 19: 5194–5201.
Meyer A, Schartl M. 1999. Gene and genome duplications in
vertebrates: the one-to-four (-to-eight in fish) rule and the
evolution of novel gene functions. Current Opinion in Cell
Biology 11: 699–704.
Meyer A, Van de Peer Y. 2003. Genome evolution: gene and
genome duplications and the origin of novel gene functions.
Berlin: Springer Verlag.
Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L,
LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr,
McCoy JM. 2000. Syncytin is a captive retroviral envelope
protein involved in human placental morphogenesis. Nature
403: 785–789.
Miller DJ, van Oppen MJH. 2003. A ‘fair go’ for coral hybridisation. Molecular Ecology 12: 805–807.
Mindell DP, Villarreal LP. 2003. Don’t forget about viruses.
Science 302: 1677.
Morgan HD et al. 1999. Epigenetic inheritance at the agouti
locus in the mouse. Nature Genetics 23: 314–318.
Morgan TH. 1911. An attempt to analyse the constitution of
the chromosomes on the basis of sex-linked inheritance in
Drosophila. Journal of Experimental Zoology 11: 365–413.
Muller HJ. 1925. Why polyploidy is rarer in animals than in
plants. American Naturalist 59: 346–353.
Nielsen MG, Wilson KA, Raff EC, Raff RA. 2000. Novel
gene expression patterns in hybrid embryos between species
with different modes of development. Evolutionary Development 2: 133–144.
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
GENOMIC CREATIVITY AND NATURAL SELECTION
Nishioka M, Hannada H. 1994. Sex of reciprocal hybrids
between the Hamakita (XX-XY type) population and the
Murakami (ZW-ZZ type) population of Rana rugosa. Science
Reports of the Laboratory for Amphibian Biology of
Hiroshima University 13: 35–50.
O’Neill RJW, Eldredge MDB, Graves JAM. 2001. Chromosome heterozygosity and de novo chromosome rearrangements in mammalian interspecies hybrids. Mammalian
Genome 12: 256–259.
O’Neill RJW, O’Neill MJ, Graves JAM. 1998. Undermethylation associated with retroelement activation and chromosome remodelling in an interspecific mammalian hybrid.
Nature 393: 68–72.
Ohno S. 1970. Evolution by gene duplication. New York, NY:
Springer.
Orr HA. 1990. ‘Why polyploidy is rarer in animals than in
plants’ revisited. American Naturalist 6: 759–770.
Otto SP, Whitton J. 2000. Polyploid incidence and evolution.
Annual Review of Genetics 34: 401–437.
Patterson N, Richter DJ, Gnerre S, Lander ES, Reich D.
2006. Genetic evidence for complex speciation of humans
and chimpanzees. Nature advance online publication at
http://www.nature.com/nature/journal/vaop/ncurrent/full/
nature04789.html.
Pebusque MJ, Coulier F, Birnhaum D, Pontarotti P.
1998. Ancient large-scale genome duplications: phylogenetic
and linkage analyses shed light on chordate genome evolution. Molecular Biology and Evolution 15: 1145–1159.
Pfenninger M, Reinhardt F, Streit B. 2002. Evidence
for cryptic hybridisation between different evolutionary
lineages of invasive clam genus Corbicula (Veneroida,
Bivalvia). Journal of Evolutionary Biology 15: 818–829.
Pollard SL, Holland PWH. 2000. Evidence of 14 homeobox
gene clusters in human genome ancestry. Current Biology
10: 1059–1062.
Provost B, Varricchio P, Arana E, Espagne E, Falabella
P, Huguet E, La Scaleia R, Cattolico L, Poirié M, Malva
C, Olszewski JA, Pennacchio F, Drezen J-M. 2004. Bracoviruses contain a large multigene family coding for protein
tyrosine phosphatases. Journal of Virology 78: 13090–13103.
Raff EC, Popodi EM, Sly BJ, Turner FR, Villinski JT,
Raff RA. 1999. A novel ontogenetic pathway in hybrid
embryos between species with different modes of development. Development 126: 1937–1945.
Raff RA. 1996. The shape of life. Chicago, IL: University of
Chicago Press, xvii.
Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan
HD, Luu KVK, Whitelaw E. 2003. Transgenerational
inheritance of epigenetic states at the murine AxinFu allele
occurs after maternal and paternal transmission. Proceedings of the National Academy of Sciences of the United States
of America 100: 2538–2543.
Rieseberg LH, Raymond O, Rosenthal DM, Lai Z, Livingstone K, Nakazato T, Durphy JL, Schwarzbach AE,
Donovan LA, Lexer C. 2003. Major ecological transitions
in annual sunflowers facilitated by hybridisation. Science
301: 1211–1216.
Rieseberg LH, Noyes RD. 1998. Genetic map-based studies
671
of reticulate evolution in plants. Trends in Plant Science 3:
254–259.
Roemer I, Reik W, Dean W, Klose J. 1997. Epigenetic inheritance in the mouse. Current Biology 7: 277–280.
Rote NS, Chakrabarti S, Stetzer BP. 2004. The role of
human endogenous retroviruses in trophoblast differentiation and placental development. Placenta 25: 673–683.
Ryan F. 2002/2003. Darwin’s blind spot. Boston, MA: US
Houghton Mifflin.
Ryan F. 2004. Human endogenous retroviruses in health and
disease: a symbiotic perspective. Journal of the Royal Society
of Medicine 97: 560–565.
Sapp J. 1994. Evolution by association: a history of symbiosis.
Oxford: Oxford University Press.
Schughart K, Kappen C, Ruddle FH. 1989. Duplication of
large genomic regions during the evolution of vertebrate
homeobox genes. Proceedings of the National Academy of Sciences of the United States of America 86: 7067–7071.
Schwartz D, Matta BM, Shakir-Botteri NL, McPheron
BA. 2005. Host shift to an invasive plant triggers rapid animal hybrid speciation. Nature 436: 546–549.
Sears KE, Behringer R, Niswander LA. 2004. The development of powered flight in Chiroptera: the morphologic and
genetic evolution of bat wing digits. Journal of Vertebrate
Paleontology 24: 111A.
Skrabanek L, Wolfe KH. 1998. Eukaryotic genome
duplication − where’s the evidence? Current Opinion in
Genetics and Development 8: 694–700.
Smith KK. 2002. Sequence heterochrony and the evolution of
development. Journal of Morphology 252: 82–97.
Soltis DE, Soltis PS. 1999. Polyploidy: recurrent formation
and genome evolution. Trends in Ecology and Evolution 14:
348–352.
Soltis PS, Soltis DE. 2000. The role of genetic and genomic
attributes in the success of polyploids. Proceedings of the
National Academy of Sciences of the United States of America
97: 7051–7057.
Sonea S. 1991. Bacterial evolution without speciation. In:
Margulis L, Fester R, ed. Symbiosis as a source of evolutionary innovation. Cambridge, MA: MIT Press.
Sonea S, Mathieu LG. 2000. Prokaryotology. Montréal: Les
Presses de l’Université de Montréal.
Spring J. 1997. Vertebrate evolution by interspecific
hybridisation − are we polyploid? Federation of European
Biochemical Societies Letters 400: 2–8.
Spring J. 2003. Major transitions in evolution by genome
fusions: from prokaryotes to eukaryotes, metazoans, bilaterians and vertebrates. Journal of Structural and Functional
Genomics 3: 19–25.
Stam M, Belele C, Ramakrishna W, Dorweiler JE, Bennetzen JL, Chandler VL. 2002. The regulatory regions
required for B′ paramutation and expression are located far
upstream of the Maize b1 transcribed sequences. Genetics
162: 917–930.
Stöck M, Lamatsch DK, Steinlein C, Epplen JT, Grosse
W-R, Hock R, Klapperstück T, Lampert KP, Scheer U,
Schmid M, Schartl M. 2002. A bisexually reproducing alltriploid vertebrate. Nature Genetics 30: 325–328.
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672
672
F. P. RYAN
Sturtevant AH. 1965. A history of genetics. New York, NY:
Harper & Row.
Sullivan JT, Ronson CW. 1998. Evolution of rhizobia by
acquisition of a 500-kb symbiosis island that integrates into
a phe-tRNA gene. Proceedings of the National Academy of
Sciences of the United States of America 95: 5145–5149.
Sverdlov ED. 2000. Retroviruses and human evolution. Bioessays 22: 161–171.
Syvanen M, Kado CI. 1998. Horizontal gene transfer. Location: Chapman & Hall.
Truman JW, Riddiford LM. 1999. The origins of insect
metamorphosis. (Hypothesis). Nature 401: 447–452.
Turner G, Barbulescu M, Su M, Jensen-Seaman MI, Kidd
KK, Lenz J. 2001. Insertional polymorphisms of full-length
endogenous retroviruses in humans. Current Biology 11:
1531–1535.
Van de Vijver G, Van Speybroeck L, De Waele D. 2002.
Epigenetics: a challenge for genetics, evolution and development? Annals of the New York Academy of Sciences 981:
1–6.
Van Oppen JH, McDonald BJ, Willis B, Miller DJ. 2001.
The evolutionary history of the coral genus Acropora (Scleractinia, Cnidaria) based on a mitochondrial and a nuclear
marker: reticulation, incomplete lineage sorting, or morphological convergence? Molecular Biology and Evolution 18:
1315–1329.
Van Speybroeck L. 2000. The organism: a crucial genomic
context in molecular epigenetics. Theory in Biosciences 119:
1–22.
Van Speybroeck L. 2002. From epigenesis to epigenetics: the
case of C.H. Waddington. Annals of the New York Academy of
Sciences 981: 61–81.
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ,
Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA
et al. 2001. The sequence of the human genome. Science
291: 1304–1351.
Villarreal LP. 2004. Are viruses alive? Scientific American
291: 101–105.
Villarreal LP. 2005. Viruses and the evolution of life American. Society for Microbiology.
Villarreal LP, DeFilippis VR. 2000. A hypothesis for DNA
viruses as the origin of eukaryotic replicative proteins. Journal of Virology 74: 7079–7084.
Walker EL. 1998. Paramutation of the r1 locus of maize is
associated with increased cytosine methylation. Genetics
148: 1973–1981.
Walter J, Paulsen M. 2003. Imprinting and disease. Seminars in Cellular and Developmental Biology 14: 101–
110.
Waterston RH, Lindblad-Toh K, Birney E, Rogers J,
Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P et al. 2002. Initial sequencing and
comparative analysis of the mouse genome. Nature 420:
560–562.
Watson JD, Crick FHC. 1953. Genetical implications of
the structure of desoxyribose nucleic acid. Nature 17: 964–
966.
Weksberg R, Smith AC, Squire J, Sadowski P. 2003. Beckwith–Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Human Molecular
Genetics 12: 61–68.
West-Eberhard MJ. 2003. Developmental plasticity and evolution. Oxford: Oxford University Press.
Whitfield JB. 1990. Parasitoids, polydnaviruses and endosymbiosis. Parasitology 6: 381–384.
Whitfield JB. 2002. Estimating the age of the polydnavirus/
braconid wasp symbiosis. Proceedings of the National
Academy of Sciences of the United States of America 99:
7508–7513.
Williamson DI. 2003. The origins of larvae. Dordrecht: Kluwer Academic Publishers.
Williamson DI. 2006. Hybridization and the Cambrian explosion. Zoological Journal of the Linnean Society in press.
Wolffe AP, Matzke MA. 1999. Epigenetics: regulation
through repression. Science 286: 481–486.
Wright S. 1931. Evolution in Mendelian populations. Genetics
16: 97–190.
Wu C, Morris JR. 2001. Genes, genetics and epigenetics: a
correspondence. Science 293: 1103–1105.
Zhao Z et al. 2000. Worldwide DNA sequence variation in a
10-kilobase noncoding region on human chromosome 22.
Proceedings of the National Academy of Sciences of the
United States of America 97: 11354–11358.
Zhou Y, Mishra B. 2003. Models of genome evolution. In:
Ciobanu G, Rozenberg G, eds. Modeling in molecular biology:
lecture notes in computer science. Berlin: Springer-Verlag.
© 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 655–672