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PMID: 15869325 Published · ppublish English Comparative Study Journal Article

A scan for positively selected genes in the genomes of humans and chimpanzees.

PLoS biology ·Vol. 3 ·No. 6 ·2005-06-00 ·Pages e170

Nielsen R, Bustamante C, Clark AG, Glanowski S, Sackton TB, Hubisz MJ, Fledel-Alon A, Tanenbaum DM, Civello D, White TJ, J Sninsky J, Adams MD, Cargill M

Abstract

Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

MeSH Terms
Animals Evolution, Molecular Genome Genome, Human Humans Likelihood Functions Pan troglodytes/genetics Polymerase Chain Reaction Selection, Genetic Zinc Fingers/genetics
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Nielsen Rasmus
Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA. [email protected]
Bustamante Carlos
Clark Andrew G
Glanowski Stephen
Sackton Timothy B
Hubisz Melissa J
Fledel-Alon Adi
Tanenbaum David M
Civello Daniel
White Thomas J
J Sninsky John
Adams Mark D
Cargill Michele
References (46)
46 references, click to expand
  1. Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment.
    Endocrinology. 1995 Jun;136(6):2770-5 PMID: 7750502
  2. Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis.
    Mol Hum Reprod. 2002 Mar;8(3):213-20 PMID: 11870228
  3. The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations.
    Genetics. 2004 Jan;166(1):351-72 PMID: 15020430
  4. Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G.
    PLoS Biol. 2004 Sep;2(9):E275 PMID: 15269786
  5. Long term trends in the evolution of H(3) HA1 human influenza type A.
    Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7712-8 PMID: 9223253
  6. Directional selection and the site-frequency spectrum.
    Genetics. 2001 Dec;159(4):1779-88 PMID: 11779814
  7. An abundance of X-linked genes expressed in spermatogonia.
    Nat Genet. 2001 Apr;27(4):422-6 PMID: 11279525
  8. Characterization of SCML1, a new gene in Xp22, with homology to developmental polycomb genes.
    Genomics. 1998 Apr 1;49(1):96-102 PMID: 9570953
  9. Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.
    Genetics. 1998 Mar;148(3):929-36 PMID: 9539414
  10. Statistical methods for detecting molecular adaptation.
    Trends Ecol Evol. 2000 Dec 1;15(12):496-503 PMID: 11114436
  11. DNA sequence and comparative analysis of chimpanzee chromosome 22.
    Nature. 2004 May 27;429(6990):382-8 PMID: 15164055
  12. PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification.
    Nucleic Acids Res. 2003 Jan 1;31(1):334-41 PMID: 12520017
  13. Strong male-driven evolution of DNA sequences in humans and apes.
    Nature. 2002 Apr 11;416(6881):624-6 PMID: 11948348
  14. Accuracy and power of statistical methods for detecting adaptive evolution in protein coding sequences and for identifying positively selected sites.
    Genetics. 2004 Oct;168(2):1041-51 PMID: 15514074
  15. An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis.
    EMBO J. 1997 May 1;16(9):2262-70 PMID: 9171341
  16. Intra- and interspecific variation in primate gene expression patterns.
    Science. 2002 Apr 12;296(5566):340-3 PMID: 11951044
  17. Evolutionary biology. Protamine wars.
    Nature. 2000 Jan 20;403(6767):261, 263 PMID: 10659834
  18. Large-scale search for genes on which positive selection may operate.
    Mol Biol Evol. 1996 May;13(5):685-90 PMID: 8676743
  19. Accelerated evolution of nervous system genes in the origin of Homo sapiens.
    Cell. 2004 Dec 29;119(7):1027-40 PMID: 15620360
  20. Large-scale analysis of the human and mouse transcriptomes.
    Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4465-70 PMID: 11904358
  21. Rapid evolution of male reproductive genes in the descent of man.
    Nature. 2000 Jan 20;403(6767):304-9 PMID: 10659848
  22. Rapid evolution of immunoglobulin superfamily C2 domains expressed in immune system cells.
    Mol Biol Evol. 1997 Jan;14(1):1-5 PMID: 9000748
  23. Genomewide comparison of DNA sequences between humans and chimpanzees.
    Am J Hum Genet. 2002 Jun;70(6):1490-7 PMID: 11992255
  24. Pervasive adaptive evolution in mammalian fertilization proteins.
    Mol Biol Evol. 2003 Jan;20(1):18-20 PMID: 12519901
  25. Population genetics of polymorphism and divergence.
    Genetics. 1992 Dec;132(4):1161-76 PMID: 1459433
  26. Sex-linked mammalian sperm proteins evolve faster than autosomal ones.
    Mol Biol Evol. 2003 Oct;20(10):1705-9 PMID: 12832636
  27. Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios.
    Science. 2003 Dec 12;302(5652):1960-3 PMID: 14671302
  28. A pseudohitchhiking model of X vs. autosomal diversity.
    Genetics. 2004 Dec;168(4):2261-9 PMID: 15611190
  29. Positive selection on the H3 hemagglutinin gene of human influenza virus A.
    Mol Biol Evol. 1999 Nov;16(11):1457-65 PMID: 10555276
  30. Frequent false detection of positive selection by the likelihood method with branch-site models.
    Mol Biol Evol. 2004 Jul;21(7):1332-9 PMID: 15014150
  31. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci.
    Genetics. 1990 Apr;124(4):967-78 PMID: 2323559
  32. Dichotomy of single-nucleotide polymorphism haplotypes in olfactory receptor genes and pseudogenes.
    Nat Genet. 2000 Oct;26(2):221-4 PMID: 11017082
  33. The signature of positive selection at randomly chosen loci.
    Genetics. 2002 Mar;160(3):1179-89 PMID: 11901132
  34. Progress in the use of microarray technology to study the neurobiology of disease.
    Nat Neurosci. 2004 May;7(5):434-9 PMID: 15114354
  35. PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing.
    Nucleic Acids Res. 1997 Jul 15;25(14):2745-51 PMID: 9207020
  36. Statistical tests of selective neutrality in the age of genomics.
    Heredity (Edinb). 2001 Jun;86(Pt 6):641-7 PMID: 11595044
  37. PAML: a program package for phylogenetic analysis by maximum likelihood.
    Comput Appl Biosci. 1997 Oct;13(5):555-6 PMID: 9367129
  38. Lineage-specific gene duplication and loss in human and great ape evolution.
    PLoS Biol. 2004 Jul;2(7):E207 PMID: 15252450
  39. Eukaryotic transcription factors: identification, characterization and functions.
    J Nutr. 1998 Nov;128(11):2045-51 PMID: 9808664
  40. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
    Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 PMID: 7984417
  41. PANTHER: a library of protein families and subfamilies indexed by function.
    Genome Res. 2003 Sep;13(9):2129-41 PMID: 12952881
  42. New explicit expressions for relative frequencies of single-nucleotide polymorphisms with application to statistical inference on population growth.
    Genetics. 2003 Sep;165(1):427-36 PMID: 14504247
  43. Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models.
    Mol Biol Evol. 2000 Jan;17(1):32-43 PMID: 10666704
  44. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection.
    Nature. 1988 Sep 8;335(6186):167-70 PMID: 3412472
  45. Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7375-9 PMID: 11404480
  46. A neutral explanation for the correlation of diversity with recombination rates in humans.
    Am J Hum Genet. 2003 Jun;72(6):1527-35 PMID: 12740762
Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
Published
2005-06-00
Epub
2005-00-03
Pages
e170
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC1088278
Subset
IM
Grants
NHGRI NIH HHS · R01 HG003229 · United States
NHGRI NIH HHS · R01 HG003229-01 · United States
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