Lambert Matthew J, Portfors Christine V
School of Biological Sciences, Washington State University, Vancouver, WA 98686, USA.
Aging (Albany NY). 2017 Feb 26;9(2):573-582. doi: 10.18632/aging.101180.
Maximum lifespan varies by two orders of magnitude across mammals. How such divergent lifespans have evolved remains an open question, with ramifications that may potentially lead to therapies for age-related diseases in humans. Several species of microbats as well as the naked mole-rat live much longer than expected given their small sizes, show reduced susceptibility to neoplasia, and largely remain healthy and reproductively capable throughout the majority of their extended lifespans. The convergent evolution of extreme longevity in these two groups allows for the opportunity to identify potentially important aging related genes that have undergone adaptive sequence convergence in these long-lived, yet small-bodied species. Here, we have tested 4,628 genes for evidence of convergence between the microbats and naked mole-rat. We find a strong signal of adaptive sequence convergence in the gene A disintegrin-like and metalloprotease with thrombospondin type 1 motifs 9 (ADAMTS9). We also provide evidence that the shared substitutions were driven by selection. Intriguingly, ADAMTS9 is a known inhibitor of the mTor pathway and has been implicated in several aging related processes.
哺乳动物的最大寿命相差两个数量级。如此不同的寿命是如何进化而来的仍然是一个悬而未决的问题，其影响可能会为人类的年龄相关疾病带来治疗方法。几种小型蝙蝠以及裸鼹鼠的寿命比根据其体型预期的要长得多，对肿瘤形成的易感性降低，并且在其延长的大部分寿命中基本保持健康且具有生殖能力。这两组动物极端长寿的趋同进化为识别在这些寿命长但体型小的物种中经历了适应性序列趋同的潜在重要衰老相关基因提供了机会。在这里，我们检测了4628个基因，以寻找小型蝙蝠和裸鼹鼠之间趋同的证据。我们在基因“含血小板反应蛋白基序的解整合素样金属蛋白酶9”（ADAMTS9）中发现了强烈的适应性序列趋同信号。我们还提供证据表明，共享的替代是由选择驱动的。有趣的是，ADAMTS9是已知的mTor通路抑制剂，并与多个衰老相关过程有关。
