Decoupled evolution of coding region and mRNA expression patterns after gene duplication: implications for the neutralist-selectionist debate.

The neutralist perspective on molecular evolution maintains that the vast majority of mutations affecting gene function are neutral or deleterious. After a gene duplication where both genes are retained, it predicts that original and duplicate genes diverge at clock-like rates. This prediction is usually tested for coding sequences, but can also be applied to another important aspect of gene function, the genes' expression pattern. Moreover, if both sequence and expression pattern diverge at clock-like rates, a correlation between divergence in sequence and divergence in expression patterns is expected. Duplicate gene pairs with more highly diverged sequences should also show more highly diverged expression patterns. This prediction is tested for a large sample of duplicated genes in the yeast Saccharomyces cerevisiae, using both genome sequence and microarray expression data. Only a weak correlation is observed, suggesting that coding sequence and mRNA expression patterns of duplicate gene pairs evolve independently and at vastly different rates. Implications of this finding for the neutralist-selectionist debate are discussed.

[1]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[2]  M. Nei,et al.  Positive Darwinian selection after gene duplication in primate ribonuclease genes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D C Shields,et al.  "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. , 1988, Molecular biology and evolution.

[4]  T. Ohta Further examples of evolution by gene duplication revealed through DNA sequence comparisons. , 1994, Genetics.

[5]  T. Jukes,et al.  The neutral theory of molecular evolution. , 2000, Genetics.

[6]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[7]  E. Kandel,et al.  Proceedings of the National Academy of Sciences of the United States of America. Annual subject and author indexes. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[9]  Xie Hong-kun,et al.  Nature of Science , 2002 .

[10]  P. W. Frank,et al.  Annual Review of Ecology and Systematics , 1972 .

[11]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[12]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[13]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Kreitman,et al.  Adaptive protein evolution at the Adh locus in Drosophila , 1991, Nature.

[15]  S. Easteal The relative rate of DNA evolution in primates. , 1991, Molecular biology and evolution.

[16]  Jeffrey S. Levinton,et al.  Molecular Evidence for Deep Precambrian Divergences Among Metazoan Phyla , 1996, Science.

[17]  R. Behringer,et al.  Mutations in paralogous Hox genes result in overlapping homeotic transformations of the axial skeleton: evidence for unique and redundant function. , 1995, Developmental biology.

[18]  J. Gillespie The causes of molecular evolution , 1991 .

[19]  A. Joyner,et al.  Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox. , 1991, Science.

[20]  L. Wolpert Developmental Biology , 1968, Nature.

[21]  H. Akashi Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. , 1994, Genetics.

[22]  Wen-Hsiung Li,et al.  The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. , 1987, Molecular biology and evolution.

[23]  K. H. Wolfe,et al.  Molecular evidence for an ancient duplication of the entire yeast genome , 1997, Nature.

[24]  B. Bainbridge,et al.  Genetics , 1981, Experientia.

[25]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[26]  D. Hartl,et al.  Codon usage bias and base composition of nuclear genes in Drosophila. , 1993, Genetics.

[27]  M. Noll,et al.  Evolution of distinct developmental functions of three Drosophila genes by acquisition of different cis-regulatory regions , 1994, Nature.

[28]  Paul M. Sharp,et al.  Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes , 1986, Nucleic Acids Res..

[29]  Nature Genetics , 1991, Nature.

[30]  D. Labie,et al.  Molecular Evolution , 1991, Nature.

[31]  Angelo Pavesi,et al.  Relationships Between Transcriptional and Translational Control of Gene Expression in Saccharomyces cerevisiae: A Multiple Regression Analysis , 1999, Journal of Molecular Evolution.

[32]  T. Gojobori,et al.  Rapid evolution of goat and sheep globin genes following gene duplication. , 1983, Molecular biology and evolution.

[33]  Kim Nasmyth,et al.  Cell cycle control of the yeast HO gene: Cis- and Trans-acting regulators , 1987, Cell.

[34]  S. Cirera,et al.  Molecular evolution of a duplication: the sex-peptide (Acp70A) gene region of Drosophila subobscura and Drosophila madeirensis. , 1998, Molecular biology and evolution.

[35]  Lipman Dj,et al.  Interaction of silent and replacement changes in eukaryotic coding sequences. , 1985 .

[36]  S. Easteal,et al.  Consistent variation in amino-acid substitution rate, despite uniformity of mutation rate: protein evolution in mammals is not neutral. , 1994, Molecular biology and evolution.

[37]  J. Marsh,et al.  Evolutionary changes in the expression pattern of a developmentally essential gene in three Drosophila species. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Kreitman,et al.  The correlation between synonymous and nonsynonymous substitutions in Drosophila: mutation, selection or relaxed constraints? , 1998, Genetics.

[39]  M. O. Dayhoff,et al.  Atlas of protein sequence and structure , 1965 .

[40]  A. R. Wagner Molecular Biology and Evolution , 2001 .

[41]  P. Schnegelsberg,et al.  Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin , 1996, Nature.

[42]  A. Wagner Robustness against mutations in genetic networks of yeast , 2000, Nature Genetics.

[43]  A. Joyner,et al.  Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. , 1995, Science.

[44]  Denis Duboule,et al.  Hox gene expression in teleost fins and the origin of vertebrate digits , 1995, Nature.

[45]  P. Chambon,et al.  Specific and redundant functions of the paralogous Hoxa-9 and Hoxd-9 genes in forelimb and axial skeleton patterning. , 1996, Development.

[46]  A. Mccarthy Development , 1996, Current Opinion in Neurobiology.

[47]  M. Capecchi,et al.  Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions , 1994, Nature.

[48]  K. G. Coleman,et al.  Expression of engrailed proteins in arthropods, annelids, and chordates , 1989, Cell.

[49]  M. Kreitman,et al.  Evolutionary dynamics of the enhancer region of even-skipped in Drosophila. , 1995, Molecular biology and evolution.

[50]  M. Long,et al.  Natural selection and the origin of jingwei, a chimeric processed functional gene in Drosophila. , 1993, Science.