Hughes Kimberly A, Alipaz Julie A, Drnevich Jenny M, Reynolds Rose M
School of Integrative Biology and Program in Ecology and Evolutionary Biology, University of Illinois, Urbana, IL 61801, USA.
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14286-91. doi: 10.1073/pnas.222326199. Epub 2002 Oct 17.
Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. The two leading theories posit that aging is due to (i) pleiotropic genes with beneficial early-life effects but deleterious late-life effects ("antagonistic pleiotropy") or (ii) mutations with purely deleterious late-life effects ("mutation accumulation"). Previous attempts to distinguish these theories have been inconclusive because of a lack of unambiguous, contrasting predictions. We conducted experiments with Drosophila based on recent population-genetic models that yield contrasting predictions. Genetic variation and inbreeding effects increased dramatically with age, as predicted by the mutation theory. This increase occurs because genes with deleterious effects with a late age of onset are unopposed by natural selection. Our findings provide the strongest support yet for the mutation theory.
细胞衰老几乎是多细胞生物的普遍特征，而理解其发生原因是生物学中一个长期存在的问题。两种主流理论认为，衰老的原因一是（i）具有有益的早期生活效应但有害的晚期生活效应的多效基因（“拮抗性多效性”），二是（ii）具有纯粹有害的晚期生活效应的突变（“突变积累”）。由于缺乏明确的、相互对比的预测，之前区分这些理论的尝试尚无定论。我们基于近期产生相互对比预测的群体遗传模型，对果蝇进行了实验。正如突变理论所预测的，遗传变异和近亲繁殖效应随年龄急剧增加。这种增加的发生是因为具有晚期发病有害效应的基因不受自然选择的抑制。我们的研究结果为突变理论提供了迄今为止最有力的支持。
