Tejada-Martinez, Daniela;
Avelar, Roberto A;
Lopes, Inês;
Zhang, Bruce;
Novoa, Guy;
de Magalhães, João Pedro;
Trizzino, Marco;
(2022)
Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.
Molecular Biology and Evolution
, 39
(2)
, Article msab369. 10.1093/molbev/msab369.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/molbev/msab369 |
| Publisher version: | https://doi.org/10.1093/molbev/msab369 |
| Language: | English |
| Additional information: | © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Keywords: | ageing, cancer, evolutionary genomics, cis-regulatory evolution, natural selections, apes, transposable elements, cell senescence |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10177229 |
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