Population history and natural selection shape patterns of genetic variation in 132 genes

Joshua M. Akey, Michael A. Eberle, Mark J. Rieder, Christopher S. Carlson, Mark D. Shriver, Deborah A. Nickerson, Leonid Kruglyak

Research output: Contribution to journalArticle

353 Citations (Scopus)

Abstract

Identifying regions of the human genome that have been targets of natural selection will provide important insights into human evolutionary history and may facilitate the identification of complex disease genes. Although the signature that natural selection imparts on DNA sequence variation is difficult to disentangle from the effects of neutral processes such as population demographic history, selective and demographic forces can be distinguished by analyzing multiple loci dispersed throughout the genome. We studied the molecular evolution of 132 genes by comprehensively resequencing them in 24 African-Americans and 23 European-Americans. We developed a rigorous computational approach for taking into account multiple hypothesis tests and demographic history and found that while many apparent selective events can instead be explained by demography, there is also strong evidence for positive or balancing selection at eight genes in the European-American population, but none in the African-American population. Our results suggest that the migration of modern humans out of Africa into new environments was accompanied by genetic adaptations to emergent selective forces. In addition, a region containing four contiguous genes on Chromosome 7 showed striking evidence of a recent selective sweep in European-Americans. More generally, our results have important implications for mapping genes underlying complex human diseases.

Original languageEnglish (US)
JournalPLoS biology
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2004

Fingerprint

Genetic Selection
natural selection
Genes
Demography
genetic variation
history
demographic statistics
African Americans
Population
genes
Chromosomes, Human, Pair 7
genome
Molecular Evolution
Chromosome Mapping
Human Genome
demography
human diseases
chromosome mapping
History
Genome

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Akey, J. M., Eberle, M. A., Rieder, M. J., Carlson, C. S., Shriver, M. D., Nickerson, D. A., & Kruglyak, L. (2004). Population history and natural selection shape patterns of genetic variation in 132 genes. PLoS biology, 2(10). https://doi.org/10.1371/journal.pbio.0020286
Akey, Joshua M. ; Eberle, Michael A. ; Rieder, Mark J. ; Carlson, Christopher S. ; Shriver, Mark D. ; Nickerson, Deborah A. ; Kruglyak, Leonid. / Population history and natural selection shape patterns of genetic variation in 132 genes. In: PLoS biology. 2004 ; Vol. 2, No. 10.
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Akey, JM, Eberle, MA, Rieder, MJ, Carlson, CS, Shriver, MD, Nickerson, DA & Kruglyak, L 2004, 'Population history and natural selection shape patterns of genetic variation in 132 genes', PLoS biology, vol. 2, no. 10. https://doi.org/10.1371/journal.pbio.0020286

Population history and natural selection shape patterns of genetic variation in 132 genes. / Akey, Joshua M.; Eberle, Michael A.; Rieder, Mark J.; Carlson, Christopher S.; Shriver, Mark D.; Nickerson, Deborah A.; Kruglyak, Leonid.

In: PLoS biology, Vol. 2, No. 10, 01.10.2004.

Research output: Contribution to journalArticle

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