Abstract
Gene duplication is commonly regarded as the main evolutionary path toward the gain of a new function. However, even with gene duplication, there is a loss-versus-gain dilemma: most newly born duplicates degrade to pseudogenes, since degenerative mutations are much more frequent than advantageous ones. Thus, something additional seems to be needed to shift the loss versus gain equilibrium toward functional divergence. We suggest that epigenetic silencing of duplicates might play this role in evolution. This study began when we noticed in a previous publication (Lynch M, Conery JS [2000] Science 291:1151–1155) that the frequency of functional young gene duplicates is higher in organisms that have cytosine methylation (H. sapiens, M. musculus, and A. thaliana) than in organisms that do not have methylated genomes (S. cerevisiae, D. melanogaster, and C. elegans). We find that genome data analysis confirms the likelihood of much more efficient functional divergence of gene duplicates in mammals and plants than in yeast, nematode, and fly. We have also extended the classic model of gene duplication, in which newly duplicated genes have exactly the same expression pattern, to the case when they are epigenetically silenced in a tissue- and/or developmental stage-complementary manner. This exposes each of the duplicates to negative selection, thus protecting from “pseudogenization.” Our analysis indicates that this kind of silencing (i) enhances evolution of duplicated genes to new functions, particularly in small populations, (ii) is quite consistent with the subfunctionalization model when degenerative but complementary mutations affect different subfunctions of the gene, and (iii) furthermore, may actually cooperate with the DDC (duplication– degeneration–complementation) process.
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References
AC Bell G Felsenfeld (2000) ArticleTitleMethylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405 482–485 Occurrence Handle10.1038/35013100 Occurrence Handle1:CAS:528:DC%2BD3cXjslykuro%3D Occurrence Handle10839546
KE Brown S Amoils JM Horn VJ Buckle DR Higgs M Merkenschlager AG Fisher (2001) ArticleTitleExpression of α-and β-globin genes occurs within different nuclear domains in haemopoetic cells. Nature Cell Biol 3 602–606 Occurrence Handle1:CAS:528:DC%2BD3MXksFelurc%3D
C-h Chiu C Amemiya K Dewar C-B Kim FH Ruddle GP Wagner (2002) ArticleTitleMolecular evolution of the HoxA cluster in the three major gnathostome lineages. Proc Natl Acad Sci USA 99 5492–5497 Occurrence Handle10.1073/pnas.052709899 Occurrence Handle1:CAS:528:DC%2BD38XjtFKltrw%3D
AG Clark (1994) ArticleTitleInvasion and maintenance of a gene duplication. Proc Natl Acad Sci USA 91 2950–2954 Occurrence Handle1:CAS:528:DyaK2cXktVantrs%3D Occurrence Handle8159686
M Cockell SM Gasser (1999) ArticleTitleNuclear compartments and gene regulation. Curr Opin Genet Dev 9 199–205 Occurrence Handle1:CAS:528:DyaK1MXisFyqtLk%3D Occurrence Handle10322139
J Crow M Kimura (1970) Introduction to population genetics theory. Harper and Row New York
RB Flavell (1994) ArticleTitleInactivation of gene expression in plants as a consequence of specific sequence duplication. Proc Natl Acad Sci USA 91 3490–3496 Occurrence Handle1:CAS:528:DyaK2cXktVajsLo%3D Occurrence Handle8170935
A Force M Lynch B Pickett A Amores Y-l Yan J Postlethwait (1999) ArticleTitlePreservation of duplicate genes by complementary, degenerative mutations. Genetics 151 1531–1545 Occurrence Handle1:CAS:528:DyaK1MXisV2rs7o%3D Occurrence Handle10101175
Z Gu D Nicolae H Lu W-H Li (2002a) ArticleTitleRapid divergence in expression between duplicate genes inferred from microarray data. Trends Genet 18 609–613 Occurrence Handle1:CAS:528:DC%2BD38XoslCgur0%3D
Z Gu A Cavalcanti F-C Chen P Bouman W-H Li (2002b) ArticleTitleExtent of gene duplication in the genomes of Drosophila, nematode, and yeast. Mol Biol Evol 19 256–262 Occurrence Handle1:CAS:528:DC%2BD38XitFSnsL4%3D
R Hardison (1998) ArticleTitleHemoglobin from bacteria to man: Evolution of different patterns of gene expression. J Exp Biol 201 1099–1117 Occurrence Handle1:CAS:528:DyaK1cXjvVOhsbg%3D Occurrence Handle9510523
PM Harrison A Kumar N Lang M Snyder M Gerstein (2002) ArticleTitleA question of size: The eukaryotic proteome and the problems in defining it. Nucleic Acids Res 30 1083–1090 Occurrence Handle1:CAS:528:DC%2BD38XitVOisLc%3D Occurrence Handle11861898
R Holliday JE Pugh (1975) ArticleTitleDNA modification mechanisms and gene activity during development. Science 187 226–232 Occurrence Handle1:CAS:528:DyaE2MXht1Sitrw%3D Occurrence Handle1111098
AL Hughes (1999) ArticleTitlePhylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history. J Mol Evol 48 565–576 Occurrence Handle1:CAS:528:DyaK1MXisFGis7o%3D Occurrence Handle10198122
T Jenuwein CD Allis (2001) ArticleTitleTranslating the histone code. Science 293 1074–1080 Occurrence Handle1:CAS:528:DC%2BD3MXmtVWltro%3D Occurrence Handle11498575
M Kimura (1971) ArticleTitleTheoretical foundation of population genetics at the molecular level. Theor Popul Biol 2 174–208 Occurrence Handle1:STN:280:CSyB2cbntVA%3D Occurrence Handle5162686
M Kimura (1983) The neutral theory of molecular evolution. Cambridge University Press Cambridge
M Kimura JL King (1979) ArticleTitleFixation of a deleterious allele at one of two “duplicate” loci by mutation pressure and random drift. Proc Natl Acad Sci USA 76 2858–2861 Occurrence Handle1:STN:280:CSaB38zovV0%3D Occurrence Handle288072
H-S Lee Z Chen (2001) ArticleTitleProtein-coding genes are epigenetically regulated in Arabidopsis polyploids. Proc Natl Acad Sci USA 98 6753–6758 Occurrence Handle1:CAS:528:DC%2BD3MXksVOku7w%3D Occurrence Handle11371624
W-H Li (1997) Molecular evolution. Sinauer Associates Sunderland, MA
W-H Li Z Gu H Wang A Nekrutenko (2001) ArticleTitleEvolutionary analysis of the human genome. Nature 409 847–849 Occurrence Handle1:CAS:528:DC%2BD3MXhsFCjtL4%3D Occurrence Handle11237007
M Lynch JS Conery (2000) ArticleTitleThe evolutionary fate and consequences of duplicate genes. Science 290 1151–1155 Occurrence Handle10.1126/science.290.5494.1151 Occurrence Handle1:CAS:528:DC%2BD3cXotVChsb8%3D Occurrence Handle11073452
M Lynch A Force (2000) ArticleTitleThe probability of duplicate gene preservation by subfunctionalization. Genetics 154 459–473 Occurrence Handle1:CAS:528:DC%2BD3cXms1KhsA%3D%3D Occurrence Handle10629003
M Lynch M O’Hely B Walsh A Force (2001) ArticleTitleThe probability of preservation of a newly arisen gene duplicate. Genetics 159 1789–1804
A Mounsey P Bauer IA Hope (2002) ArticleTitleEvidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. Genome Res 12 770–775 Occurrence Handle1:CAS:528:DC%2BD38XjvFSgtL0%3D Occurrence Handle11997343
JH Nadeau D Sankoff (1997) ArticleTitleComparative rates of gene loss and functional divergence after genome duplications early in vertebrate evolution. Genetics 147 1259–1266 Occurrence Handle1:STN:280:DyaK1c%2FktlCitA%3D%3D Occurrence Handle9383068
M Nei AK Roychoudhury (1973) ArticleTitleProbability of fixation of nonfunctional genes at duplicate loci. Am Nat 107 362–372
S Ohno (1970) Evolution by gene duplication. Springer Berlin
T Ohta (1987) ArticleTitleSimulating evolution by gene duplication. Genetics 115 207–213 Occurrence Handle1:STN:280:BiiC28zksVM%3D Occurrence Handle3557113
VA Ratner AA Zharkikh NA Kolchanov SN Rodin VV Solovyov AS Antonov (1996) Molecular evolution. Springer Berlin
AD Riggs (1975) ArticleTitleX-inactivation, differentiation and DNA methylation. Cytogenet Cell Genet 14 9–25
AD Riggs TN Porter (1996) Overview of epigenetic mechanisms. EA Russo RA Martienssen AD Riggs (Eds) Epigenetic mechanisms of gene regulation. Cold Spring Harbor Laboratory Press New York 29–45
SN Rodin (1991) Idea of coevolution. Nauka Novosibirsk (in Russian)
JL Rossignol G Faugeron (1994) ArticleTitleGene inactivation triggered by recognition between DNA repeats. Experientia 50 307–317 Occurrence Handle1:CAS:528:DyaK2cXjtFKktb0%3D Occurrence Handle8143804
A Sadhu ML Shen M Hackbarth E Hume TW McKeithan (1997) ArticleTitleCpG-rich sequences close to the site of duplication within the human IGH constant region. Immunogenetics 45 365–370 Occurrence Handle1:CAS:528:DyaK2sXjt12ltrs%3D Occurrence Handle9089093
N Skaer D Pistillo J-M Gibert P Lio C Wulbeck P Simpson () ArticleTitleGene duplication at the achaete-scute complex and morphological complexity of the peripheral nervous system in Diptera. Trends Genet 18 399–405
S Tweedie J Charlton V Clark A Bird (1997) ArticleTitleMethylation of genomes and genes at the invertebrate-vertebrate boundary. Mol Cell Biol 17 1469–1475 Occurrence Handle1:CAS:528:DyaK2sXhtlGmsLg%3D Occurrence Handle9032274
JC Venter et al. (2001) ArticleTitleThe sequence of the human genome. Science 21 1304–1351
A Wagner (1998) ArticleTitleThe fate of duplicated genes: loss or new function? BioEssays 20 785–788 Occurrence Handle10.1002/(SICI)1521-1878(199810)20:10<785::AID-BIES2>3.0.CO;2-M Occurrence Handle1:STN:280:DyaK1M3gs1emug%3D%3D Occurrence Handle10200118
A Wagner (2001) ArticleTitleBirth and death of duplicated genes in completely sequenced eukaryotes. Trends Genet 17 237–239 Occurrence Handle1:CAS:528:DC%2BD3MXjtFCltbo%3D Occurrence Handle11335019
JB Walsh (1995) ArticleTitleHow often do duplicated genes evolve new functions? Genetics 139 421–428 Occurrence Handle1:STN:280:ByqB38%2FmvVQ%3D Occurrence Handle7705642
KH Wolfe (2001) ArticleTitleYesterday’s polyploids and the mystery of diplodization. Nature Rev Genet 2 333–341 Occurrence Handle1:CAS:528:DC%2BD3MXjtlGjs7g%3D
AP Wolffe MA Matzke (1999) ArticleTitleEpigenetics: Regulation through repression. Science 286 481–486
Acknowledgements
We are very thankful to Andrew Rodin for valuable suggestions and help with the statistical treatment of data. This work was supported by NIH Grant GM 50575.
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Rodin, S.N., Riggs, A.D. Epigenetic Silencing May Aid Evolution by Gene Duplication . J Mol Evol 56, 718–729 (2003). https://doi.org/10.1007/s00239-002-2446-6
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DOI: https://doi.org/10.1007/s00239-002-2446-6