Adaptive Evolution Hotspots at the GC-Extremes of the Human Genome: Evidence for Two Functionally Distinct Pathways of Positive Selection

We recently reported that the human genome is ‘‘splitting” into two gene subgroups characterised by polarised GC content (Tang et al, 2007), and that such evolutionary change may be accelerated by programmed genetic instability (Zhao et al, 2008). Here we extend this work by mapping the presence of two separate high-evolutionary-rate (Ka/Ks) hotspots in the human genome—one characterized by low GC content, high intron length, and low gene expression, and the other by high GC content, high exon number, and high gene expression. This finding suggests that at least two different mechanisms mediate adaptive genetic evolution in higher organisms: (1) intron lengthening and reduced repair in hypermethylated lowly-transcribed genes, and (2) duplication and/or insertion events affecting highly-transcribed genes, creating low-essentiality satellite daughter genes in nearby regions of active chromatin. Since the latter mechanism is expected to be far more efficient than the former in generating variant genes that increase fitnesss, these results also provide a potential explanation for the controversial value of sequence analysis in defining positively selected genes.

[1]  E. Eichler,et al.  Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution , 2007, Nature Genetics.

[2]  L. Horth.  Sensory genes and mate choice: evidence that duplications, mutations, and adaptive evolution alter variation in mating cue genes and their receptors. , 2007, Genomics.

[3]  A. Hughes,et al.  Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level , 2007, Heredity.

[4]  H. Kokko,et al.  WHEN NOT TO AVOID INBREEDING , 2006, Evolution; international journal of organic evolution.

[5]  Justin C. Fay,et al.  Evaluating the role of natural selection in the evolution of gene regulation , 2008, Heredity.

[6]  H. Philippe,et al.  Heterotachy and Functional Shift in Protein Evolution , 2003, IUBMB life.

[7]  E. Danchin,et al.  Conceptual bases for quantifying the role of the environment on gene evolution: the participation of positive selection and neutral evolution , 2007, Biological reviews of the Cambridge Philosophical Society.

[8]  J A Koziol,et al.  Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Smith,et al.  Intron length and accelerated 3' gene evolution. , 2006, Genomics.

[10]  Jianzhi Zhang,et al.  On the Evolution of Codon Volatility , 2005, Genetics.

[11]  Jianzhi Zhang,et al.  Gene Complexity and Gene Duplicability , 2005, Current Biology.

[12]  John S. Conery,et al.  The evolutionary demography of duplicate genes , 2004, Journal of Structural and Functional Genomics.

[13]  R. Frankham.  Stress and adaptation in conservation genetics , 2005, Journal of evolutionary biology.

[14]  A. Hughes.  Near Neutrality , 2008, Annals of the New York Academy of Sciences.

[15]  E. Koonin,et al.  Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. , 2002, Genome research.

[16]  A. Vinogradov.  ‘Genome design’ model and multicellular complexity: golden middle , 2006, Nucleic acids research.

[17]  M. Lynch,et al.  The evolutionary fate and consequences of duplicate genes. , 2000, Science.

[18]  David L Stern,et al.  Is Genetic Evolution Predictable? , 2009, Science.

[19]  M. MacCoss,et al.  Duplication and selection on abalone sperm lysin in an allopatric population. , 2007, Molecular biology and evolution.

[20]  R. Epstein,et al.  A Structural Split in the Human Genome , 2007, PloS one.

[21]  A. Wagner.  Robustness, evolvability, and neutrality , 2005, FEBS letters.

[22]  J. Drake.  Mutations in clusters and showers , 2007, Proceedings of the National Academy of Sciences.

[23]  Manel Camps,et al.  Genetic Constraints on Protein Evolution , 2007, Critical reviews in biochemistry and molecular biology.

[24]  J. Mattick,et al.  The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms. , 2001, Molecular biology and evolution.

[25]  Leo Goodstadt,et al.  Eukaryotic domain evolution inferred from genome comparisons. , 2003, Current opinion in genetics & development.

[26]  E. Koonin,et al.  Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world , 2008, Nucleic acids research.

[27]  W. Swanson,et al.  Pervasive Adaptive Evolution in Primate Seminal Proteins , 2005, PLoS genetics.

[28]  Fengtang Yang,et al.  Copy number variation and evolution in humans and chimpanzees. , 2008, Genome research.

[29]  L. Hurst,et al.  Molecular evolution of an imprinted gene: repeatability of patterns of evolution within the mammalian insulin-like growth factor type II receptor. , 1998, Genetics.

[30]  J. Petrosino,et al.  Adaptive Amplification and Point Mutation Are Independent Mechanisms: Evidence for Various Stress-Inducible Mutation Mechanisms , 2004, PLoS biology.

[31]  J. Roth,et al.  Adaptive mutation: General mutagenesis is not a programmed response to stress but results from rare coamplification of dinB with lac , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  D. Parkhomchuk,et al.  Position-Associated GC Asymmetry of Gene Duplicates , 2004, Journal of Molecular Evolution.

[33]  Alan R Templeton,et al.  The reality and importance of founder speciation in evolution. , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[35]  E. Neidle,et al.  Selection for gene clustering by tandem duplication. , 2003, Annual review of microbiology.

[36]  J. Roth,et al.  Ohno's dilemma: Evolution of new genes under continuous selection , 2007, Proceedings of the National Academy of Sciences.

[37]  Yongzhong Zhao,et al.  Programmed Genetic Instability: A Tumor-Permissive Mechanism for Maintaining the Evolvability of Higher Species through Methylation-Dependent Mutation of DNA Repair Genes in the Male Germ Line , 2008, Molecular biology and evolution.

[38]  W. Patrick,et al.  Natural history as a predictor of protein evolvability. , 2006, Protein engineering, design & selection : PEDS.

[39]  Eugene V Koonin,et al.  Mutational hotspots in the TP53 gene and, possibly, other tumor suppressors evolve by positive selection , 2006, Biology Direct.

[40]  H. Innan,et al.  Selection for more of the same product as a force to enhance concerted evolution of duplicated genes. , 2006, Trends in genetics : TIG.

[41]  Claus O. Wilke,et al.  Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-Sequence Evolution , 2008, Cell.

[42]  Alex Wong,et al.  Approaches for identifying targets of positive selection. , 2007, Trends in genetics : TIG.