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Detecting Natural Selection at the Molecular Level: A Reexamination of Some “Classic” Examples of Adaptive Evolution

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Abstract

An important criterion used to detect adaptive evolution in DNA sequence data is ω i > 1, where ω i is the ratio of nonsynonymous to synonymous substitution rates in lineage i. However, the evaluation of multiple ω i within a phylogenetic tree can easily inflate the statistical type I error rate. We developed two rigorous methods of analysis that avoid this and other potential pitfalls. We applied these methods to four published examples of adaptive evolution. One case was strongly supported by our reanalysis (abalone sperm lysin), and one was weakly supported (baboon α-globin), but two examples (primate lysozyme and Antarctic fish β-globin) did not show significant evidence of adaptive evolution. Our first method is a “bottom-up” hierarchical maximum likelihood approach, which (1) tests for significant heterogeneity in ω across the phylogeny, (2) locates its source using a sequence of planned comparisons, and (3) tests homogeneous groups of ω for ω > 1, using a modified level of significance that incorporates the pretesting. The second method is a “top-down” log-linear analysis based on estimates of nonsynonymous and synonymous substitutions in pairs of lineages. The log-linear test is applied to pairs of lineages joined at progressively deeper nodes. For each pair, the analysis simultaneously tests for adaptive evolution (ω > 1), a shift in natural selection (ω1 ≠ω2), and unequal evolution rate (the relative rate test). In both tests, we emphasized that the criterion ω1 ≠ ω2 is an important additional indicator of a phylogenetic shift in the balance between natural selection and genetic drift between two related lineages.

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References

  • Akashi H (1999) Within- and between-species DNA sequence variation and the ‘footprint’ of natural selection. Gene 238:39–51

    Article  CAS  PubMed  Google Scholar 

  • Anisimova M, Beilawski JP, Yang Z (2001) Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution. Mol Biol Evol 18:1585–1592

    CAS  PubMed  Google Scholar 

  • Bargelloni L, Marcato S, Patarnello T (1998) Antarctic fish hemoglobins: evidence for adaptive evolution at subzero temperature. Proc Natl Acad Sci USA 95:8070–8675

    Article  Google Scholar 

  • Bousquet J, Strauss SH, Doerkesen A, Price R (1992) Extensive variation in evolutionary rate of rbcL gene sequencing among seed plants. Proc Natl Acad Sci USA 89:7844–7848

    CAS  PubMed  Google Scholar 

  • Britten RJ (1986) Rates of DNA sequence evolution differ between taxonomic groups. Science 231:5974–5978

    Google Scholar 

  • Clark AG, Glanowski S, Nielsen R, Thomas PD, Kejariwal A, Todd MA, Tanenbaum DM, Civello D, Lu F, Murphy B, Ferriera S, Wang G, Zheng X, White TJ, Sninsky JJ, Adams MD, Cargill M (2003) Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. Science 302:1960–1963

    Article  CAS  PubMed  Google Scholar 

  • Crandall KA, Kelsey CR, Imamichi H, Lane HC, Salzman NP (1999) Parallel evolution of drug resistance in HIV: Failure of nonsynonymous/synonymous substitution rate ratio to detect selection. Mol Biol Evol 16:372–382

    CAS  PubMed  Google Scholar 

  • Endo T, Ikeo K, Gojobori T (1996) Large-scale search for genes on which positive selection may operate. Mol Biol Evol 13:685–690

    CAS  PubMed  Google Scholar 

  • Felsenstein J (1985) Phylogenies and the comparative method. Am Natr 125:1–15

    Article  Google Scholar 

  • Galindo BE, Vacquier VD, Swanson WJ (2003) Positive selection in the egg receptor for abalone sperm lysin. Proc Natl Acad Sci USA 100:4639–4643

    Article  CAS  PubMed  Google Scholar 

  • Gillespie JH (1991) The causes of molecular evolution. Oxford University Press, New York

    Google Scholar 

  • Goldman N, Yang Z (1994) A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11:725–736

    CAS  PubMed  Google Scholar 

  • Guindon S, Rodrigo AG, Dyer KA, Huelsenbeck JP (2004) Modeling the site-specific variation of selection patterns along lineages. Proc Natl Acad Sci USA 101:12957–12962

    Article  CAS  PubMed  Google Scholar 

  • Huelsenbeck JP, Dyer KA (2004) Bayesian estimation of positively selected sites. J Mol Evol 58:661–672

    Article  CAS  PubMed  Google Scholar 

  • Hughes AL, Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167–170

    CAS  PubMed  Google Scholar 

  • Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, New York

    Google Scholar 

  • Kohne DE (1970) Evolution of higher-organism DNA. Q Rev Biophys 33:327–375

    Google Scholar 

  • Knoke D, Burke PJ (1980) Log-linear models. Sage, Beverly Hills, CA

    Google Scholar 

  • Kumar S, Tamura K, Jakobsen IB, Nei M (2001) MEGA2: Molecular Evolutionary Genetics Analysis software. Bioinformatics 17:1244–1245

    Article  CAS  PubMed  Google Scholar 

  • Lee Y-H, Vacquier VD (1992) The divergence of species-specific abalone sperm lysins is promoted by positive Darwinian selection. Biol Bull 182:97–104

    CAS  Google Scholar 

  • Lee Y-H, Ota T, Vacquier VD (1995) Positive selection is a general phenomenon in the evolution of abalone sperm lysin. Mol Biol Evol 12:231–238

    CAS  PubMed  Google Scholar 

  • Lewontin RC, Felsenstein J (1965) The robustness of homogeneity in 2 × n tables. Biometrics 21:19–33

    Google Scholar 

  • Li W-H (1997) Molecular evolution. Sinauer Associates, Sunderland, MA

    Google Scholar 

  • Li W-H, Graur D (1991) Fundamentals of molecular evolution. Sinauer Associates, Sunderland, MA

    Google Scholar 

  • Martin AP, Palumbi SR (1993) Body size, metabolic rate, generation time and the molecular clock. Proc Natl Acad Sci USA 90:4087–4091

    CAS  PubMed  Google Scholar 

  • Messier W, Stewart C-B (1997) Episodic adaptive evolution of primate lysozyme. Nature 385:151–154

    Article  CAS  PubMed  Google Scholar 

  • Moran NA (1996) Accelerated evolution and Muller’s rachet in endosymbiotic bacteria. Proc Natl Acad Sci USA 93:2873–2878

    Article  CAS  PubMed  Google Scholar 

  • Muse SV, Gaut BS (1997) Comparing patterns of nucleotide substitution rates among chloroplast loci using the relative ratio test. Genetics 146:393–399

    CAS  PubMed  Google Scholar 

  • Nei M, Gojobori T (1986) Simple methods for estimating the number of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426

    CAS  PubMed  Google Scholar 

  • Nielsen R (2001) Statistical tests of selective neutrality in the age of genomics. Heredity 86:641–647

    Article  CAS  PubMed  Google Scholar 

  • Nielsen R, Yang ZH (1998) Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148:929–936

    CAS  PubMed  Google Scholar 

  • Rice WR (1989) Analyzing tables of statistical tests. Evolution 43:223–225

    Google Scholar 

  • Sarich VM, Wilson AC (1973) Generation time and genomic evolution in primates. Science 179:1144–1147

    CAS  PubMed  Google Scholar 

  • Sharp PM (1997) In search of molecular darwinism. Nature 385:111–112

    Article  PubMed  Google Scholar 

  • Shaw J-P, Marks J, Shen CC, Shen C-KJ (1989) Anomalous and selective DNA mutations in the Old World monkey α-globin genes. Proc Natl Acad Sci USA 86:1312–1316

    CAS  PubMed  Google Scholar 

  • Sokal R, Rohfl FJ (1995) Biometry: the principles and practice of statistics in biological research, 3rd ed. W.H. Freeman, New York

    Google Scholar 

  • Suzuki Y, Gojobori T (1999) A method for detecting positive selection at single amino acid sites. Mol Biol Evol 16:1315–1328

    CAS  PubMed  Google Scholar 

  • Swofford DL (2002) PAUP*. Phylogenetic Analysis Using Parsimony (*and other methods). Version 4. Sinauer Associates, Sunderland, MA

    Google Scholar 

  • Tamura K, Nei M, Kumar S (2004) Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA 101:11030–11035

    CAS  PubMed  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 24:4876–4882

    Google Scholar 

  • Wong WSW, Yang Z, Goldman N, Nielson R (2004) Accuracy and power of statistical methods for detecting adaptive evolution in protein coding sequences and for identifying positively selected sites. Genetics 168:1041–1051

    Article  CAS  PubMed  Google Scholar 

  • Wu C-I, Li W-H (1985) Evidence for higher rates of nucleotide substitution in rodents than in man. Proc Natl Acad Sci USA 82:1741–1745

    CAS  PubMed  Google Scholar 

  • Yang Z (1997) PAML, a program package for phylogenetic analysis by maximum likelihood. CABIOS 13:306–314

    Google Scholar 

  • Yang Z (1998) Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 15:568–573

    CAS  PubMed  Google Scholar 

  • Yang Z, Bielawski JP (2000) Statistical methods for detecting molecular adaptation. Trends Evol Ecol 15:496–503

    Article  Google Scholar 

  • Yang Z, Nielsen R (2002) Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol 19:908–917

    CAS  PubMed  Google Scholar 

  • Yang Z, Nielsen R, Goldman N, Pedersen A-MK (2000) Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 155:431–449

    CAS  PubMed  Google Scholar 

  • Zhang J (2003) Parallel functional changes in the digestive RNases of ruminants and colobines by divergent amino acid substitutions. Mol Biol Evol 20:1310–1317

    CAS  PubMed  Google Scholar 

  • Zhang J (2004) Frequent false detection of positive selection by the likelihood method with branch-site models. Mol Biol Evol 21:1332–1339

    CAS  PubMed  Google Scholar 

  • Zhang J, Kumar S, Nei M (1997) Small-sample tests of episodic adaptive evolution: a case study of primate lysozyme. Mol Biol Evol 14:1335–1338

    CAS  PubMed  Google Scholar 

  • Zhang J, Rosenberg HF, Nei M (1998) Positive Darwinian selection after gene duplication in primate ribonuclease genes. Proc Natl Acad Sci USA 95:3708–3713

    CAS  PubMed  Google Scholar 

  • Zuckerkandl E, Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Bryson V, Vogel HJ (eds). Evolving genes and proteins. Academic Press, New York, pp 97–165

    Google Scholar 

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Acknowledgments

We are grateful to the two anonymous reviewers for their thorough and helpful comments.

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Authors and Affiliations

  1. Department of Biology, University of California, Riverside, CA, 92521, USA

    Leonard Nunney & Erin L. Schuenzel

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  1. Leonard Nunney
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  2. Erin L. Schuenzel
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Correspondence to Leonard Nunney.

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[Reviewing Editor: Dr. John Huelsenbeck]

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Nunney, L., Schuenzel, E.L. Detecting Natural Selection at the Molecular Level: A Reexamination of Some “Classic” Examples of Adaptive Evolution. J Mol Evol 62, 176–195 (2006). https://doi.org/10.1007/s00239-004-0334-y

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  • DOI: https://doi.org/10.1007/s00239-004-0334-y

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