Developmental rewiring via new gene origination
Yong Edward Zhang
Computational & Evolutionary Genomics Group
Key Laboratory of Zoological Systematics and Evolution
Institute of Zoology, CAS
http://zhanglab.ioz.ac.cn
Oct. 15, 2014
Outline
1. Background: new genes tend to be neglected
partially due to the propaganda of Evo Devo
2. Progress: integrative omics demonstrated the
prevalence of new genes and their functional
importance in development
Definition of new gene
Synonyms: young gene, gene origination or gene gain.
Old
New gene origination
Young
Species A
Species B
Species C
The golden age of computational
evolutionary genomics is coming
Przeworski, M. (2011) Science
New genes are generally under-characterized in
functional studies, but why?
Zhang, Y, et al.(2012) BioEssays
Reason 1: high-throughput platforms were
biased to old genes
Zhang, Y, et al.(2012) BioEssays
Reason 2: new genes generally have narrower
and lower expression
Zhang, Y, et al.(2012) BioEssays
Reason 3: new gene origination is not important
Gene duplication is infrequent.
Carrol, S. (2005) PLoS Bio.
Conservation is equal to function.
Monroe, D. (2009) Science
Outline
1. Background: new genes tend to be neglected partially due to
the propaganda of Evo Devo
2. Progress: integrative omics demonstrated the prevalence of
new genes and their functional importance in development
•
•
Various mechanisms contribute to a high flux of new
gene addition to the evolving genome.
New gene could be essential in fly and human
development.
Major molecular mechanisms for
creating new gene structures
Long, M. et al (2003) Nature Rev. Genet.
Recent multiple rounds of DNA-based duplication
shapes the subtelomere of Oryza sativa chromosome 3
short arm
New
Old
Fan, C*, Zhang, Y*, et al. (2008) Mol Plant.
Structural renovation mediated by RNA-based
duplication (retroposition) in Arabidopsis and Populus
Intronization
Zhu, Z, Zhang, Y, et al. (2009) Plant Physiol.
FLJ33706, a tale of de novo origination
Splicing structure
Open reading frame
Jacob, F. (1977) Science
Li, C, Zhang, Y, et al. (2010) PLoS Comput. Biol.
How did de novo gene get originated?
“a new de novo protein-coding gene may have
evolved from a previously expressed noncoding
sequence.”
Cai, J. et al (2008) Genetics
“The DNA must become transcribed and it must
also gain a translatable ORF. These steps may
occur in either order.”
Knowles, D & McLysaght, A. (2009) Genome Res.
Genome-wide screen of hominoid-specific de
novo genes
Xie, C*, Zhang, Y*, et al. (2012) PLoS Genet.
De novo gene emerges from long noncoding RNAs
Xie, C*, Zhang, Y*, et al. (2012) PLoS Genet.
Gene gain is prevalent
Zhang, Y, et al.(2012) BioEssays
Outline
1. Background: new genes tend to be neglected partially due to
the propaganda of Evo Devo
2. Progress: integrative omics demonstrated the prevalence of
new genes and their functional importance in development
•
•
Various mechanisms contribute to a high flux of new
gene addition to the evolving genome.
New gene could be essential in fly and human
development.
Question
New genes are known to be essential for male
reproduction. Could they contribute to a more
conserved process, i.e., development?
Ding, Y., et al. (2010) PLoS Genet.
Chen, S. et al. (2012) Embl J.
…
Inference of gene ages based on syntenic
genomic alignment
Zhang,Y. et al. (2010) Genome Res.
Genome-wide age dating in D.melanogaster
Zhang,Y, et al. (2010) Genome Res.
Surprisingly, new genes are as important as old genes
for fruitfly development
Proportion of
essential genes
Age groups (myr)
Chen, S., Zhang ,Y. , Long, M. (2010) Science
Knock-down of new genes often result in
pupal lethality
Metamorphosis is highly evolvable in
terms of gene gain
Domazet-Lošo, T & Tautz, D (2010) Nature
The essentiality of new genes may be caused by the coevolution of the whole molecular network
Ni, X, Zhang, Y, et al.(2012) PLoS Bio.
Question
Could new gene be also manifested in human
development?
Genome-wide age dating in human and mouse
Human
Mouse
Zhang, Y, et al.(2010) PLoS Bio.
Human brain demonstrates an excess of new
gene expression relative to mouse
Zhang, Y. et al. (2011) PLoS Bio.
Random sub-sampling shows that such a excess could
not be discounted by excess of human brain EST
Zhang, Y. et al. (2011) PLoS Bio.
Excess of new gene expression in human is
mainly contributed by fetal brain
Zhang, Y. et al.(2011) PLoS Bio.
Excess of new gene transcription is
specific to human fetal brain
Zhang, Y. et al. (2011) PLoS Bio.
RNA-seq, microarray and SAGE data confirms the enrichment
of new genes in human early developing brain
Zhang, Y. et al. (2011) PLoS Bio.
Which brain region recruits an excess
of new genes ?
Johnson, MB et al (2009) Neuron
Which brain regions recruits an excess
of new genes ? (continued)
Zhang, Y. et al.(2011) PLoS Bio.
New genes upregulated in developing neocortex is highly
enriched with primate-specific transcription factors
Zhang, Y. et al.(2011) PLoS Bio.
New gene origination parallels the
morphological evolution of brain
Zhang, Y. et al.(2011) PLoS Bio.
Human-specific genes are indeed involved
in brain development
Charrier, C. et al.(2012) Cell
Summary: new gene quickly invades into the
developmental pathway
Outline
1. Background: new genes tend to be neglected partially due to
the propaganda of Evo Devo
2. Progress: integrative omics demonstrated the prevalence of
new genes and their functional importance in development
•
•
Various mechanisms contribute to a high flux of new
gene addition to the evolving genome.
New gene could be essential in fly and human
development.
Question
Comparative omics revealed the generality of gene
gain in evolution and the functional significance of
new genes for fly development or human brain
development. Thus, although there are deeply
conserved tool kit genes, some of them may be quite
young. Does it mean Evo-devo is wrong?
Recruit of new gene in development
challenges the Evo Devo “revolution”
• King, M and Wilson, A (1975) Science: Protein is so similar
between human and chimpanzee and thus regulatory
evolution is the main driver underlying their difference.
• Carroll, S (2000) Cell: Cis-regulatory evolution is more
important than changes in gene number or protein
function.
Carroll, S (2005) Endless forms most beautiful: the new science
of evo devo and the making of the animal kingdom
New gene origination can also
minimize the pleiotropy
Carroll, S (2006) PLoS Bio.
Take home message
1. Human and mouse only share 70%~80% of
their genetic makeup due to massive gene
gain and loss.
2. New gene origination is able to minimize
pleiotropy just like the so-called genetic
switch or enhancer.
Acknowledgement
University of Chicago
Peking University
NIH
Manyuan Long
Chuanyun Li
Tim Liu
Maria Vibranovski
Zhenglin Zhu
Mikko Airavaara
Sidi Chen
Patrick Landback
Xiaochun Ni
Many thanks. Any question is welcome!
Email: [email protected]