Positive selection and enhancer evolution shaped lifespan and body mass in great apes

Daniela Tejada-martinez, Roberto A Avelar, Inês Lopes, Bruce Zhang, Guy Novoa, João Pedro De Magalhães, Marco Trizzino, Harmit Malik (Editor)

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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.

Original languageEnglish
Article numbermsab369
Number of pages16
JournalMolecular Biology and Evolution
Issue number2
Early online date31 Dec 2021
Publication statusPublished - Feb 2022

Bibliographical note

Funding Information:
This study was funded by NIH R35 GM138344-01, awarded to M.T. AnAge, GenAge, and CellAge are supported by funding from the Biotechnology and Biological Sciences Research Council (BB/R014949/1) to J.P.M. The authors are grateful to Alejandra Tejada-Martinez for the graphical support.

Publisher Copyright:
© 2021 The Author(s).


  • ageing
  • apes
  • cancer
  • cell senescence
  • cis-regulatory evolution
  • evolutionary genomics
  • natural selections
  • transposable elements

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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