Document Type
Article
Publication Date
2-3-2022
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.
Recommended Citation
Tejada-Martinez, Daniela; Avelar, Roberto A; Lopes, Inês; Zhang, Bruce; Novoa, Guy; de Magalhães, João Pedro; and Trizzino, Marco, "Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes" (2022). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 204.
https://jdc.jefferson.edu/bmpfp/204
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
34971383
Language
English
Comments
This article is the author’s final published version in Molecular biology and evolution, Volume 39, Issue 2, February 2022.
The published version is available at https://doi.org/10.1093/molbev/msab369. Copyright © Tejada-Martinez et al.