Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes

Tejada-Martinez, Daniela, Avelar, Roberto A ORCID: 0000-0003-4997-9953, Lopes, Ines, Zhang, Bruce, Novoa, Guy, de Magalhaes, Joao Pedro ORCID: 0000-0002-6363-2465 and Trizzino, Marco
(2022) Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes. MOLECULAR BIOLOGY AND EVOLUTION, 39 (2). msab369-.

Access the full-text of this item by clicking on the Open Access link.


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.

Item Type: Article
Uncontrolled Keywords: ageing, cancer, evolutionary genomics, cis-regulatory evolution, natural selections, apes, transposable elements, cell senescence
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 22 Feb 2022 08:21
Last Modified: 18 Jan 2023 21:11
DOI: 10.1093/molbev/msab369
Open Access URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88378...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3149381