Molecular evolution of growth hormone and insulin-like growth factor 1 receptors in long-lived, small-bodied mammals
Molecular evolution of growth hormone and insulin-like growth factor 1 receptors in long-lived, small-bodied mammals
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DOI：
10.1016/j.gene.2014.07.061
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发表时间：
2014-10-10
期刊：
影响因子：
3.5
通讯作者：
Rossiter, Stephen J.
中科院分区：
文献类型：
--
作者：
Davies, Kalina T. J.;Tsagkogeorga, Georgia;Rossiter, Stephen J.
哺乳动物的寿命和体型之间通常表现出强有力的正相关关系。蝙蝠和非洲鼹鼠是两个明显偏离这一模式的群体，这两个群体的成员都非常长寿，因为它们的体型，许多物种的最长寿命超过20年。最近的一项基因组学研究，特别长寿的布兰德蝙蝠，鼠耳蝠（41岁），表明其长寿和小的身体大小可能至少部分归因于关键氨基酸取代的跨膜结构域的受体生长激素（GH）和胰岛素样生长因子1（IGF 1）。然而，尽管所有19个蝙蝠家族的长寿可能都很普遍，但报告的氨基酸替换仅在两个密切相关的蝙蝠家族中观察到。为了验证这一假设，即改变GH/IGF 1轴与非洲鼹鼠和蝙蝠的寿命，我们比较和分析了同源编码基因序列的基因组和转录组数据从26蝙蝠种，5鼹鼠和38外类群物种。这两个基因的系统发育分析恢复了目前公认的物种树中的大部分节点，支持率很高。与其他分支相比，如灵长类和食肉动物，蝙蝠和啮齿动物有更长的分支长度。发现IGF 1 R的单个24个氨基酸跨膜结构域在哺乳动物中比GHR更保守。在蝙蝠中，GHR的跨膜结构域的相当大的变化被发现，包括以前未报告的删除Emballonuridae。啮齿类动物的跨膜结构域被认为是更保守的，鼹鼠缺乏独特的保守氨基酸取代。分子进化分析表明，这两个基因在蝙蝠和鼹鼠中处于净化选择状态。我们的研究结果表明，虽然先前记录的突变可能会赋予鼠耳蝠一些额外的寿命，但其他未知的遗传差异可能会解释在许多蝙蝠和鼹鼠物种中观察到的长寿命。(C)2014爱思唯尔有限公司版权所有。
Mammals typically display a robust positive relationship between lifespan and body size. Two groups that deviate markedly from this pattern are bats and African mole-rats, with members of both groups being extremely long-lived given their body size, with the maximum documented lifespan for many species exceeding 20 years. A recent genomics study of the exceptionally long-lived Brand's bat, Myotis brandtii (41 years), suggested that its longevity and small body size may be at least partly attributed to key amino acid substitutions in the transmembrane domains of the receptors of growth hormone (GH) and insulin-like growth factor 1 (IGF1). However, whereas elevated longevity is likely to be common across all 19 bat families, the reported amino acid substitutions were only observed in two closely related bat families. To test the hypothesis that an altered GH/IGF1 axis relates to the longevity of African mole-rats and bats, we compared and analysed the homologous coding gene sequences in genomic and transcriptomic data from 26 bat species, five mole-rats and 38 outgroup species. Phylogenetic analyses of both genes recovered the majority of nodes in the currently accepted species tree with high support. Compared to other clades, such as primates and carnivores, the bats and rodents had longer branch lengths. The single 24 amino acid transmembrane domain of IGF1R was found to be more conserved across mammals compared to that of GHR. Within bats, considerable variation in the transmembrane domain of GHR was found, including a previously unreported deletion in Emballonuridae. The transmembrane domains of rodents were found to be more conserved, with mole-rats lacking uniquely conserved amino acid substitutions. Molecular evolutionary analyses showed that both genes were under purifying selection in bats and mole-rats. Our findings suggest that while the previously documented mutations may confer some additional lifespan to Myotis bats, other, as yet unknown, genetic differences are likely to account for the long lifespans observed in many bat and mole-rat species. (C) 2014 Elsevier B.V. All rights reserved.