Changing effective population size and the McDonald-Kreitman test.

Artifactual evidence of adaptive amino acid substitution can be generated within a McDonald-Kreitman test if some amino acid mutations are slightly deleterious and there has been an increase in effective population size. Here I investigate the conditions under which this occurs. I show that fairly small increases in effective population size can generate artifactual evidence of positive selection if there is no selection upon synonymous codon use. This problem is exacerbated by the removal of low-frequency polymorphisms. However, selection on synonymous codon use restricts the conditions under which artifactual evidence of adaptive evolution is produced.

[1]  P. Keightley,et al.  Deleterious mutations and the evolution of sex. , 2000, Science.

[2]  Daniel J. Gaffney,et al.  Quantifying the slightly deleterious mutation model of molecular evolution. , 2002, Molecular biology and evolution.

[3]  H. Akashi,et al.  Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. , 1999, Genetics.

[4]  Feng-Chi Chen,et al.  Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. , 2001, American journal of human genetics.

[5]  D. Hartl,et al.  Population genetics of polymorphism and divergence. , 1992, Genetics.

[6]  K. Holsinger The neutral theory of molecular evolution , 2004 .

[7]  S. Wright,et al.  The Distribution of Gene Frequencies Under Irreversible Mutation. , 1938, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Whitlock,et al.  The probability of fixation in populations of changing size. , 1997, Genetics.

[9]  M. Stoneking,et al.  Nonneutral mitochondrial DNA variation in humans and chimpanzees. , 1996, Genetics.

[10]  S. Easteal,et al.  Departure from neutrality at the mitochondrial NADH dehydrogenase subunit 2 gene in humans, but not in chimpanzees. , 1998, Genetics.

[11]  P. Andolfatto Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. , 2001, Molecular biology and evolution.

[12]  D. L. Jenkins,et al.  A test for adaptive change in DNA sequences controlling transcription , 1995, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[13]  M. Kimura,et al.  The neutral theory of molecular evolution. , 1983, Scientific American.

[14]  Justin C. Fay,et al.  Testing the neutral theory of molecular evolution with genomic data from Drosophila , 2002, Nature.

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

[16]  C. Aquadro,et al.  African and North American populations of Drosophila melanogaster are very different at the DNA level , 1993, Nature.

[17]  Justin C. Fay,et al.  Positive and negative selection on the human genome. , 2001, Genetics.

[18]  R. Kliman Recent Selection on Synonymous Codon Usage in Drosophila , 1999, Journal of Molecular Evolution.

[19]  Laurence D. Hurst,et al.  The evolution of isochores , 2001, Nature Reviews Genetics.

[20]  Adam Eyre-Walker,et al.  Adaptive protein evolution in Drosophila , 2002, Nature.

[21]  S. Schaeffer,et al.  Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila. , 1997, Genetics.

[22]  B. Charlesworth The effect of background selection against deleterious mutations on weakly selected, linked variants. , 1994, Genetical research.

[23]  D. Begun,et al.  The frequency distribution of nucleotide variation in Drosophila simulans. , 2001, Molecular biology and evolution.

[24]  M. Bulmer The selection-mutation-drift theory of synonymous codon usage. , 1991, Genetics.

[25]  H. Akashi,et al.  Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. , 1996, Genetics.