4.5 Article

Analyses of human-chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging

Journal

MECHANISMS OF AGEING AND DEVELOPMENT
Volume 128, Issue 5-6, Pages 355-364

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2007.03.004

Keywords

comparative genomics; life history; longevity; natural selection

Funding

  1. NHGRI NIH HHS [P50 HG003170-03, P50 HG003170-02, P50 HG003170-01, P50 HG003170] Funding Source: Medline

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Compared to chimpanzees (Pan troglodytes), the onset of aging appears to be delayed in the human species. Herein, we studied human-chimpanzee orthologous gene pairs to investigate the selective forces acting on genes associated with aging in different model systems, which allowed us to explore evolutionary hypotheses of aging. Our results show that aging-associated genes tend to be under purifying selection and stronger-than-average functional constraints. We found little evidence of accelerated evolution in aging-associated genes in the hominid or human lineages, and pathways previously related to aging were largely conserved between humans and chimpanzees. In particular, genes associated with aging in non-mammalian model organisms and cellular systems appear to be under stronger functional constraints than those associated with aging in mammals. One gene that might have undergone rapid evolution in hominids is the Werner syndrome gene. Overall, our findings offer novel insights regarding the evolutionary forces acting on genes associated with aging in model systems. We propose that genes associated with aging in model organisms may be part of conserved pathways related to pleiotropic effects on aging that might not regulate species differences in aging. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

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