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

Abstract

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.

Figure 1

Approximate limit of detection of rapid evolution using our test statistic as a function of sequence length and K_a/K_s ratio. The straight black line represents the K_a/K_s ratio threshold above which a given protein-coding sequence will be detected as undergoing rapid evolution. Sequence length, which may be a single gene or a concatenated sequence of a large group of genes (the average human-chimpanzee gene pair, only including the protein-coding sequence, is approximately 1.4 kb), is plotted on a logarithmic scale. The dotted gray line is the average K_a/K_s ratio for all human-chimpanzee gene pairs (0.23). K_a/K_s ratios assume a constant K_s and a constant proportion of synonymous and nonsynonymous sites in relation to sequence length, both of which were estimated from the average of all human-chimpanzee gene pairs.