Update
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References
1 Marcuello, E. et al. (2004) Single nucleotide polymorphism in the
5 0 tandem repeat sequences of thymidylate synthase gene predicts for
response to fluorouracil-based chemotherapy in advanced colorectal
cancer patients. Int. J. Cancer 112, 733–737
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alignment of noncoding DNA sequences based on an evolutionary
model of sequence evolution. Genome Res. 14, 442–450
0168-9525/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tig.2005.08.001
Cnidarians and ancestral genetic complexity in the
animal kingdom
David J. Miller1, Eldon E. Ball2 and Ulrich Technau3
1
Comparative Genomics Centre, Molecular Sciences Building 21, James Cook University, Townsville, Queensland 4811, Australia
Centre for the Molecular Genetics of Development and Molecular Genetics and Evolution Group,
Research School of Biological Sciences, Australian National University, P.O Box 475, Canberra, ACT2601, Australia
3
Sars International Centre for Marine Molecular Biology, Thormøhlensgt. 55, 5008 Bergen, Norway
2
Eleven of the twelve recognized wingless (Wnt) subfamilies are represented in the sea anemone Nematostella
vectensis, indicating that this developmentally important
gene family was already fully diversified in the common
ancestor of ‘higher’ animals. In deuterostomes, although
duplications have occurred, no novel subfamilies of Wnts
have evolved. By contrast, the protostomes Drosophila
and Caenorhabditis have lost half of the ancestral Wnts.
This pattern – loss of genes from an ancestrally complex
state – might be more important in animal evolution than
previously recognized.
Introduction
One of the most deep-rooted assumptions in animal biology
is that the evolution of vertebrate characteristics, such as a
sophisticated humoral immune system, the neural crest and
a highly complex nervous system, was enabled by new sets of
genes. This notion appears legitimate when mammals are
compared with the model ecdysozoans Drosophila and
Caenorhabditis but, as we learn more about the genetic
makeup of additional organisms, the list of ‘vertebratespecific’ genes seems to be shrinking by the day. The
broadening of comparative genomics to include animals
such as the sea anemone Nematostella vectensis, the coral
Corresponding author: Miller, D.J. ([email protected]).
Available online 11 August 2005
www.sciencedirect.com
Acropora millepora (both members of the cnidarian Class
Anthozoa) and the ragworm Platynereis dumerilii
(Annelida, Polychaeta) requires some radical rethinking of
traditional assumptions about the origins of many vertebrate genes. There have been intriguing hints that some
‘vertebrate-specific’ genes might predate the origin of the
Bilateria (see Glossary) [1–4], and this point is elegantly
made in a recent paper on wingless (Wnt) gene diversity in
Nematostella [5], which broadens, and pushes back in
time, the conclusions previously reached for the same gene
family by Prud’homme et al. [6].
Glossary
Cnidaria: a basal phylum, traditionally characterized as having two body layers,
radial symmetry and being at the tissue grade of morphological organisation.
The defining characteristic of the phylum is the presence of a nematocyst, or
stinging cell. There are two basic morphologies; the sessile polyp and the
swimming medusa or jellyfish. The phylum contains four classes, the basal
Anthozoa, to which the sea anemone Nematostella and the coral Acropora
belong, the Cubozoa or ‘sea wasps’, the Scyphozoa, or ‘true’ jellyfish, and the
Hydrozoa, which includes the familiar freshwater Hydra.
Bilateria: a monophyletic group of metazoan animals characterized by bilateral
symmetry. This group, which could also be termed the ‘higher Metazoa’
excludes the Cnidaria, Ctenophora, Porifera (sponges) and Placozoa.
Oral–aboral axis: the single obvious body axis of the two ‘radiate’ phyla
(Cnidaria and Ctenophora), marked at one end by the mouth or oral pore.
Deuterostomes: those bilaterians in which the anus opens near the former site
of the blastopore.
Protostomes: those bilaterians in which the mouth opens near the former site
of the blastopore.
Update
TRENDS in Genetics Vol.21 No.10 October 2005
Anthozoan cnidarians such as Nematostella are proving to be particularly informative for inferring the gene
content of the common cnidarian–bilaterian ancestor,
because this class of cnidarians is basal within the phylum
[7] (reviewed in Ref. [8]). The genome of Nematostella has
been sequenced, and is currently being assembled.
Undoubtedly, there are more surprises to come, but the
limited data currently available for Nematostella and
other cnidarians provide some intriguing hints at the
probable genetic complexity of the common metazoan
ancestor. An article by Kusserow et al. [5], based on work
from the Holstein and Martindale laboratories, reveals
that at least eleven of the twelve Wnt families known from
chordates are present in Nematostella (hence predating
the Cnidaria–Bilateria split) and elegantly shows that
most of these genes are expressed in serially overlapping
expression domains along the primary (oral–aboral) body
axis. Only six of the twelve Wnt families are represented
in the model ecdysozoans, Drosophila and Caenorhabditis,
which underscores the extent of gene loss in these
organisms [3,9].
The results of Kusserow et al. [5] are important in
several ways. First, the article is refreshingly comprehensive. Expression patterns of each of the twelve genes at
five stages of Nematostella development are presented and
because all of the in situ analysis hybridisation experiments were performed using similar techniques in only
two laboratories, many of the uncertainties usually
associated with comparing expression patterns between
laboratories were eliminated. Second, as the authors
recognize, the expression patterns of the genes indicate
a system that might be capable of patterning the oral–
aboral axis, because restricted zones of expression span
the oral two-thirds of the axis in both ectoderm and
endoderm. This contrasts with the expression of the
currently known Nematostella Hox-like genes [10],
which appear incapable of playing a role in patterning
comparable to the Hox genes of ‘higher’ animals, particularly in the ectoderm, because they are expressed, with
a single exception, exclusively in the endoderm. Third, in
spite of the diverse roles of Wnts across the Bilateria,
Kusserow et al. could recognize certain conserved expression patterns. For example, the Nematostella ectodermal
genes, NvWnt1, NvWnt2, NvWnt4 and NvWnt7 correspond to the neuroectodermal Wnt genes in the higher
Bilateria. Another example cited, which is however less
clearcut owing to a diversity of expression patterns in
deuterostomes, is that NvWnt5, NvWnt6 and NvWnt8 are
expressed in the endoderm, whereas the corresponding
genes in deuterostomes are all expressed in the mesoderm.
Another possible example of conservation that can be
investigated, as a result of the sequencing of the Nematostella genome, is whether the chromosomally linked,
evolutionarily conserved cluster of WNT1–WNT6–WNT10
mentioned by Nusse [11] is conserved in Nematostella.
The genetic complexity of the common metazoan
ancestor
The Wnts are one of six families of signaling molecules
that are responsible for most developmental cell–cell
interactions across the animal kingdom [12]. The
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537
Nematostella data indicate that full diversification of the
Wnt family preceded the origin of the Bilateria (Figure 1),
and ongoing EST and genome projects for various
cnidarians will show whether this is also the case for the
other five developmentally regulated signaling pathways
[i.e. transforming growth factor b (TGFb), Ras–mitogenactivated protein kinase 1 (MAPK), nuclear receptor,
notch and hedgehog]. Recent studies have identified
components of the TGFb [10,13], Ras–MAPK (reviewed
in Ref. [1]) and nuclear hormone receptor families [14].
Although uncertainties remain regarding notch and
hedgehog, the currently available data imply that much
of the diversity of cell signaling associated with ‘higher’
animals was actually achieved early in animal evolution.
Moreover, at least some of the ‘vertebrate-specific’
antagonists of these signaling pathways have much
earlier origins than was inferred based on their absence
from Drosophila and Caenorhabditis [15]. Clear homologs
of the vertebrate Wnt antagonist Dickkopf are represented in EST collections for the jellyfish Cyanea [16]
and Hydra ([4] and publicly available Hydra EST data
sets; http://hydra.ics.uci.edu/jf). Similarly, probable homologs of the gene encoding the bone morphogenetic protein
(BMP) antagonist Noggin have been identified in the
planarian Dugesia [17] and the sponge Suberites [18],
indicating that it too might also have an ancient origin.
The presence of potential antagonists means that one
cannot predict that a Wnt signaling pathway is active
based solely on expression pattern because of the complex
regulatory reactions of the Wnts [19]. It seems likely that
there are certain time windows during development when
Wnt expression is particularly important, but these will
only be revealed once the techniques to selectively knock
out individual Wnt genes have been developed. However,
in situ expression analyses of the candidate Wnt
antagonists using currently available techniques should
reveal some aspects of how the system might be working
in Nematostella.
Do losses outweigh gains?
One important general implication of the Nematostella
Wnt study and several other recent articles is that they
highlight the significance of gene loss during animal
evolution. Drosophila and Caenorhabditis have lost half of
the ancestral Wnt diversity [5], and many other genes [3]
found in ‘lower’ animals, but chordates have also undergone gene loss, as is most clearly evident in the lower
chordates Ciona and Oikopleura [20]. Each new EST study
reveals further examples of gene loss at every taxonomic
level throughout the ‘higher’ Metazoa. For example, of
5021 cDNAs from the honeybee (Apis mellifera), 23 were
uniquely shared with mammals, indicating that these
genes were present in the common ancestor of ‘higher’
animals, but have been lost from Drosophila, Anopheles
and Caenorhabditis [21]. Furthermore, of the 674
sequences identified as ‘chordate-specific’ on the basis of
being present in Ciona, Fugu and human but absent from
Caenorhabditis and Drosophila [22], almost half can now
be identified in ecdysozoans. It is difficult to escape the
conclusion that the genome of the common ancestor of
‘higher’ animals was surprisingly complex in terms of
538
Update
TRENDS in Genetics Vol.21 No.10 October 2005
Bilateria
Chordata
Ciona, Oikopleura, Fugu
Hemichordata
Deuterostomia
Echinodermata
Brachiopoda
Mollusca
Lottia
Lophotrochozoa
Annelida
Platynereis, Helobdella, Capitella
Protostomia
Nemertea
Platyhelminthes
Dugesia
Arthropoda
Drosophila, Anopheles, Apis
Nematoda
Ecdysozoa
Caenorhabditis
Cnidaria
Ctenophora
Porifera
Reniera, Suberites
Bilateria
Anthozoa
Acropora, Nematostella
Circular mt
genomes
Hydrozoa
Hydra
Linear mt
genomes
Cubozoa
Scyphozoa
Cyanea
TRENDS in Genetics
Figure 1. Phylogenies of the animal kingdom (upper panel) and Cnidaria (lower panel). Animal phylogeny has been revised in recent years on the basis of molecular data; the
overall phylogeny shown has been modified from Ref. [23]. The positions of the Cnidaria and Ctenophora relative to the Bilateria are uncertain. The major phyla are listed and
the higher groupings discussed in the main text are indicated by the coloured boxes. Genera mentioned in the main text are listed under the phylum to which they belong.
The symbols used are courtesy of the Integration and Application Network (ian.umces.edu/symbols), University of Maryland Center for Environmental Science. Within the
Cnidaria, based on molecular evidence, it is clear that the Class Anthozoa is basal. Abbreviation: mt, mitochondrial.
gene content, and that gene loss has been a major factor in
genome evolution since divergence from the common
ancestor.
Concluding remarks
The probable availability of complete genome sequences
for the sponge Reniera and several cnidarians (Nematostella, Hydra and possibly also a coral) within the next
year or so should clarify the extent of ancestral genetic
complexity within the animal kingdom. One key outstanding issue concerns the other major protostome
lineage, the Lophotrochozoa (Figure 1): have gene loss
and sequence divergence been as extensive as in the
Ecdysozoa, or have ancestral states been more faithfully
maintained? There are hints from studies of specific gene
families (e.g. Ref. [6]) that losses might have been less
www.sciencedirect.com
extensive in some lophotrochozoans than in those ecdysozoans that we are familiar with. The evo-devo community
awaits, with great interest, the completion of full genome
sequencing projects in progress for several lophotrochozoans, including the annelids Helobdella and Capitella, and
the mollusc Lottia, which are scheduled for completion
during 2005 by the DOE’s Joint Genome Institute (http://
www.jgi.doe.gov/).
References
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2 Bosch, T.C.G. and Khalturin, K. (2002) Patterning and cell differentiation in Hydra: novel genes and the limits to conservation. Canad.
J. Zool. 80, 1670–1677
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TRENDS in Genetics Vol.21 No.10 October 2005
3 Kortschak, R.D. et al. (2003) EST analysis of the cnidarian Acropora
millepora reveals extensive gene loss and rapid sequence divergence
in the model invertebrates. Curr. Biol. 13, 2190–2195
4 Fedders, H. et al. (2004) A Dickkopf-3-related gene is expressed in
differentiating nematocysts in the basal metazoan Hydra. Dev. Genes
Evol. 214, 72–80
5 Kusserow, A. et al. (2005) Unexpected complexity of the Wnt gene
family in a sea anemone. Nature 433, 156–160
6 Prud’homme, B. et al. (2002) Phylogenetic analysis of the Wnt
gene family: insights from lophotrochozoan members. Curr. Biol.
12, 1395–1400
7 Collins, A.G. (2002) Phylogeny of Medusozoa and the evolution of
cnidarian life cycles. J. Evol. Biol. 15, 418–432
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rearrangement in nematodes than in Drosophila. Genome Res. 12,
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expression in a sea anemone. Science 304, 1335–1337
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pathways in animal development. Nat. Rev. Genet. 4, 39–49
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ortholog in a coral embryo. Proc. Natl. Acad. Sci. U. S. A. 99,
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18 Müller, W.E.G. et al. (2003) Origin of metazoan stem cell system in
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19 Moon, R.T. et al. (1997) Structurally related receptors and antagonists
compete for secreted Wnt ligands. Cell 88, 725–728
20 Edvardsen, R.B. et al. (2005) Remodelling of the homeobox gene
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0168-9525/$ - see front matter Crown Copyright Q 2005 Published by Elsevier Ltd. All rights
reserved.
doi:10.1016/j.tig.2005.08.002
Novel patterns of gene expression in polyploid plants
Keith L. Adams1 and Jonathan F. Wendel2
1
UBC Botanical Garden and Centre for Plant Research, 2357 Main Mall, MacMillan Building, University of British Columbia,
Vancouver, British Colombia, Canada, V6T 1Z4
2
Department of Ecology, Evolution and Organismal Biology, Iowa State University, Ames, IA 50011, USA
Genome doubling, or polyploidy, is a major factor
accounting for duplicate genes found in most eukaryotic
genomes. Polyploidy has considerable effects on duplicate gene expression, including silencing and up- or
downregulation of one of the duplicated genes. These
changes can arise with the onset of polyploidization or
within several generations after polyploid formation
and they can have epigenetic causal factors. Many
expression alterations are organ-specific. Specific
genes can be independently and repeatedly silenced
during polyploidization, whereas patterns for other
genes appear to be more stochastic. Three recent
reports have provided intriguing new insights into the
patterns, timing and mechanisms of gene expression
changes that accompany polyploidy in plants.
Introduction
Most eukaryotic genomes have numerous duplicated
genes, many of which appear to have arisen from one or
Corresponding authors: Adams, K.L. ([email protected]), Wendel, J.F.
( [email protected]).
Available online 10 August 2005
www.sciencedirect.com
more cycles of polyploidy (genome doubling), either by
allopolyploidy or autopolyploidy (see Glossary). Welldocumented examples of polyploidy exist in various
groups of vertebrates, insects, yeasts and plants [1,2].
Ancient polyploidy events (paleopolyploidy) have been
inferred to have occurred during the evolutionary history
of vertebrates, yeast and flowering plants [3]. Following
paleopolyploidy there has been extensive loss of duplicated genes. Polyploidy has been especially common in
flowering plants, where most species are inferred to have
experienced at least one polyploidy event in their
evolutionary history [4]. For example, at least two and
probably three paleopolyploidy events are thought to
have occurred during the evolutionary history of Arabidopsis thaliana [5]. Approximately 27% of the gene pairs
that were formed by polyploidy have been retained in
A. thaliana [6] and more than half of these gene pairs
show evidence of functional divergence [7].
The merging and doubling of two genomes sets in
motion extensive modifications of the genome and/or transcriptome, creating cascades of novel expression patterns,
regulatory interactions and new phenotypic variation for
evaluation by natural selection [5,8,9]. Recent studies