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Article
Adaptive Evolution of a Candidate Gene for Aging in Drosophila
Proceedings of the National Academy of Sciences
  • Paul S. Schmidt
  • David D. Duvernell, Missouri University of Science and Technology
  • Walter F. Eanes
Abstract

Examination of the phenotypic effects of specific mutations has been extensively used to identify candidate genes affecting traits of interest. However, such analyses do not reveal anything about the evolutionary forces acting at these loci, or whether standing allelic variation contributes to phenotypic variance in natural populations. The Drosophila gene methuselah (mth) has been proposed as having major effects on organismal stress response and longevity phenotype. Here, we examine patterns of polymorphism and divergence at mth in population level samples of Drosophila melanogaster, D. simulans, and D. yakuba. Mth has experienced an unusually high level of adaptive amino acid divergence concentrated in the intra- and extracellular loop domains of the receptor protein, suggesting the historical action of positive selection on those regions of the molecule that modulate signal transduction. Further analysis of single nucleotide polymorphisms (SNPs) in D. melanogaster provided evidence for contemporary and spatially variable selection at the mth locus. In ten surveyed populations, the most common mth haplotype exhibited a 40% cline in frequency that coincided with population level differences in multiple life-history traits including lifespan. This clinal pattern was not associated with any particular SNP in the coding region, indicating that selection is operating at a closely linked site that may be involved in gene expression. Together, these consistently nonneutral patterns of inter- and intraspecific variation suggest adaptive evolution of a signal transduction pathway that may modulate lifespan in nature.

Department(s)
Biological Sciences
Keywords and Phrases
  • aging,
  • amino acid sequence,
  • Drosophila,
  • Drosophila melanogaster,
  • Drosophila simulans,
  • evolution,
  • gene expression,
  • gene locus,
  • genetics,
  • haplotype,
  • lifespan,
  • longevity,
  • nonhuman,
  • nucleotide sequence,
  • phenotype,
  • priority journal,
  • sequence analysis,
  • signal transduction,
  • single nucleotide polymorphism,
  • stress,
  • Adaptation,
  • Biological,
  • Aging,
  • Animal,
  • Drosophila,
  • Evolution,
  • Molecular,
  • Genes,
  • Insect,
  • Insect Proteins,
  • Molecular Sequence Data,
  • Receptors,
  • Cell Surface,
  • Support,
  • U.S. Gov't,
  • P.H.S.
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2000 National Academy of Sciences, All rights reserved.
Publication Date
9-1-2000
Publication Date
01 Sep 2000
Disciplines
Citation Information
Paul S. Schmidt, David D. Duvernell and Walter F. Eanes. "Adaptive Evolution of a Candidate Gene for Aging in Drosophila" Proceedings of the National Academy of Sciences Vol. 97 Iss. 20 (2000) p. 10861 - 10865 ISSN: 0027-8424
Available at: http://works.bepress.com/david-duvernell/9/