A method to find longevity-selected positions in the mammalian proteome.
A method to find longevity-selected positions in the mammalian proteome.
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DOI：
10.1371/journal.pone.0038595
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Grishin NV
中科院分区：
文献类型：
--
作者：
Semeiks J;Grishin NV
进化论认为，自然选择的力量随着年龄的增长而减弱。为了探索这种预测直接影响蛋白质结构和功能的程度，我们使用多元回归来找到长寿选择的位置，定义为在长寿但不短命的哺乳动物物种中保守的序列比对的列。我们分析了33种哺乳动物中的7，590个正向同源蛋白家族，包括体重、遗传和物种特异性突变率。总的来说，我们发现哺乳动物蛋白质组中长寿选择位置的数量比偶然预期的要高得多。此外，这些位置富集在几种蛋白质的结构域中，这些蛋白质在炎症和其他衰老相关过程以及生物体发育中相互作用。我们目前作为一个例子，抗苗勒管激素2型受体（AMHR 2）的激酶结构域。AMHR 2抑制卵泡募集和生长，激酶结构域的同源模型显示其长寿选择位置聚集在与人类绝经延迟相关的SNP附近。与其在发育中的典型作用不同，AMHR 2的这一区域可能以寿命特异性方式调节蛋白质的活性。
Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conserved in long-lived but not short-lived mammal species. We analyzed 7,590 orthologous protein families in 33 mammalian species, accounting for body mass, phylogeny, and species-specific mutation rate. Overall, we found that the number of longevity-selected positions in the mammalian proteome is much higher than would be expected by chance. Further, these positions are enriched in domains of several proteins that interact with one another in inflammation and other aging-related processes, as well as in organismal development. We present as an example the kinase domain of anti-Müllerian hormone type-2 receptor (AMHR2). AMHR2 inhibits ovarian follicle recruitment and growth, and a homology model of the kinase domain shows that its longevity-selected positions cluster near a SNP associated with delayed human menopause. Distinct from its canonical role in development, this region of AMHR2 may function to regulate the protein’s activity in a lifespan-specific manner.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
4.8
作者：
Manev, H;Uz, T;Qu, TY
通讯作者：
Qu, TY
影响因子：
10.7
作者：
Jobson, Richard W.;Nabholz, Benoit;Galtier, Nicolas
通讯作者：
Galtier, Nicolas
影响因子：
5.6
作者：
Jones, DT
通讯作者：
Jones, DT
影响因子：
5.8
作者：
Arnold, K;Bordoli, L;Schwede, T
通讯作者：
Schwede, T