Functional and Adaptive Significance of Promoter Mutations That Affect Divergent Myocardial Expressions of TRIM72 in Primates.
Functional and Adaptive Significance of Promoter Mutations That Affect Divergent Myocardial Expressions of TRIM72 in Primates.
复制标题
影响灵长类动物 TRIM72 不同心肌表达的启动子突变的功能和适应性意义。
DOI：
10.1093/molbev/msab083
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发表时间：
2021-06-25
影响因子：
10.7
通讯作者：
Xiao RP
中科院分区：
文献类型：
--
作者：
Feng Y;Xu H;Liu J;Xie N;Gao L;He Y;Yao Y;Lv F;Zhang Y;Lu J;Zhang W;Li CY;Hu X;Yang Z;Xiao RP
顺式调控元件在组织特异性基因表达和各种表型的进化中起重要作用，启动子和增强子的突变可能是物种适应环境的原因。TRIM72是一种高度保守的蛋白质，参与能量代谢。它在心脏中的表达在灵长类动物中变化很大，在旧大陆猴中表达水平很高，而在原始人中几乎不存在。在这里，我们结合联合收割机系统发育假设检验和实验，以证明启动子的突变是负责心脏特异性表达的灵长类物种之间的差异TRIM 72。最大似然估计的谱系特定的替代率本地时钟模型下显示，相对于内含子的进化速率，启动子的速率加快了78%，在旧大陆猴的共同祖先，这表明积极选择的作用，在TRIM72启动子的进化，可能是由选择压力，由于在物种分化后心脏生理的变化。我们证明了TRIM72启动子的突变导致了人类和恒河猴心肌TRIM72的差异表达。此外，TRIM72表达的变化改变了参与氧化磷酸化的基因的表达，从而影响线粒体呼吸和心脏能量容量。在更广泛的时间尺度上，来自29种哺乳动物物种的数据的系统发育回归分析显示，心脏高表达TRIM72的哺乳动物具有高心率，这表明TRIM72的表达变化可能与这些物种的心脏生理学差异有关。
Cis-regulatory elements play important roles in tissue-specific gene expression and in the evolution of various phenotypes, and mutations in promoters and enhancers may be responsible for adaptations of species to environments. TRIM72 is a highly conserved protein that is involved in energy metabolism. Its expression in the heart varies considerably in primates, with high levels of expression in Old World monkeys and near absence in hominids. Here, we combine phylogenetic hypothesis testing and experimentation to demonstrate that mutations in promoter are responsible for the differences among primate species in the heart-specific expression of TRIM72. Maximum likelihood estimates of lineage-specific substitution rates under local-clock models show that relative to the evolutionary rate of introns, the rate of promoter was accelerated by 78% in the common ancestor of Old World monkeys, suggesting a role for positive selection in the evolution of the TRIM72 promoter, possibly driven by selective pressure due to changes in cardiac physiology after species divergence. We demonstrate that mutations in the TRIM72 promoter account for the differential myocardial TRIM72 expression of the human and the rhesus macaque. Furthermore, changes in TRIM72 expression alter the expression of genes involved in oxidative phosphorylation, which in turn affects mitochondrial respiration and cardiac energy capacity. On a broader timescale, phylogenetic regression analyses of data from 29 mammalian species show that mammals with high cardiac expression of TRIM72 have high heart rate, suggesting that the expression changes of TRIM72 may be related to differences in the heart physiology of those species.
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DOI：
10.1073/pnas.1016959108
发表时间：
2011-04-05
影响因子：
11.1
作者：
He, Aibin;Kong, Sek Won;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Kim TK;Shiekhattar R
通讯作者：
Shiekhattar R
影响因子：
30.8
作者：
Haygood, Ralph;Fedrigo, Olivier;Awray, Gregory
通讯作者：
Awray, Gregory
影响因子：
16.6
作者：
Anderson DJ;Kaplan DI;Bell KM;Koutsis K;Haynes JM;Mills RJ;Phelan DG;Qian EL;Leitoguinho AR;Arasaratnam D;Labonne T;Ng ES;Davis RP;Casini S;Passier R;Hudson JE;Porrello ER;Costa MW;Rafii A;Curl CL;Delbridge LM;Harvey RP;Oshlack A;Cheung MM;Mummery CL;Petrou S;Elefanty AG;Stanley EG;Elliott DA
通讯作者：
Elliott DA