Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.
Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.
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DOI：
10.1093/molbev/msab369
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发表时间：
2022-02-03
影响因子：
10.7
通讯作者：
Trizzino M
中科院分区：
文献类型：
--
作者：
Tejada-Martinez D;Avelar RA;Lopes I;Zhang B;Novoa G;de Magalhães JP;Trizzino M
在灵长类动物中，大猿在体型和寿命方面都是离群者，因为它们包括了该目中最大和寿命最长的物种。然而，这些特征背后的分子基础却知之甚少。在这里，我们利用一种综合方法来研究灵长类动物中分子变异的多种来源，重点关注超过10，000个基因，包括大约1，500个以前与寿命相关的基因，以及另外大约9，000个从未被提出与寿命相关的基因。我们分析了dN/dS率、阳性选择、基因表达（RNA-seq）和基因调控（ChIP-seq）。通过分析dN/dS、最大寿命和体重之间的相关性，我们确定了276个基因，它们的进化速度与灵长类动物的最大寿命呈正相关。此外，我们确定了五个基因，对肿瘤抑制，适应性免疫，转移和炎症很重要，只在大猿谱系中进行正向选择。从代表所有灵长类谱系的六个物种的肝脏中产生的RNA-seq数据显示，与其他灵长类动物相比，以前与长寿相关的约1，500个基因中有8%在猿中差异表达。重要的是，通过将RNA-seq与H3 K27 ac的ChIP-seq（标记活性增强子）整合，我们表明差异表达的长寿基因比预期的更有可能位于新的“猿特异性”增强子附近。此外，这些特定的猿特异性增强子富含年轻的转座因子，特别是SINE-Vntr-Alus。总之，我们证明了多种进化力量对灵长类动物寿命和体型的进化做出了贡献。
Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel “ape-specific” enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE–Vntr–Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.
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影响因子：
16.6
作者：
Chatsirisupachai K;Lesluyes T;Paraoan L;Van Loo P;de Magalhães JP
通讯作者：
de Magalhães JP
DOI：
10.1093/bioinformatics/btx063
发表时间：
2017-06-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Brown JW;Walker JF;Smith SA
通讯作者：
Smith SA
DOI：
10.1001/jama.2015.13134
发表时间：
2015-11-03
期刊：
JAMA
影响因子：
--
作者：
Abegglen LM;Caulin AF;Chan A;Lee K;Robinson R;Campbell MS;Kiso WK;Schmitt DL;Waddell PJ;Bhaskara S;Jensen ST;Maley CC;Schiffman JD
通讯作者：
Schiffman JD
DOI：
10.1126/science.aad5497
发表时间：
2016-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chuong EB;Elde NC;Feschotte C
通讯作者：
Feschotte C
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y