Research Paper Volume 10, Issue 4 pp 561—572

The evolution of CpG density and lifespan in conserved primate and mammalian promoters

Adam T. McLain 1, , Christopher Faulk 2, ,

  • 1 Department of Biology and Chemistry, College of Arts and Sciences, SUNY Polytechnic Institute, Utica, NY 13502, USA
  • 2 Department of Animal Sciences, University of Minnesota, College of Food, Agricultural, and Natural Resource Sciences, Saint Paul, MN 55108, USA

received: February 19, 2018 ; accepted: April 9, 2018 ; published: April 14, 2018 ;
How to Cite

Copyright: McLain and Faulk. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Gene promoters are evolutionarily conserved across holozoans and enriched in CpG sites, the target for DNA methylation. As animals age, the epigenetic pattern of DNA methylation degrades, with highly methylated CpG sites gradually becoming demethylated while CpG islands increase in methylation. Across vertebrates, aging is a trait that varies among species. We used this variation to determine whether promoter CpG density correlates with species’ maximum lifespan. Human promoter sequences were used to identify conserved regions in 131 mammals and a subset of 28 primate genomes. We identified approximately 1000 gene promoters (5% of the total), that significantly correlated CpG density with lifespan. The correlations were performed via the phylogenetic least squares method to account for trait similarity by common descent using phylogenetic branch lengths. Gene set enrichment analysis revealed no significantly enriched pathways or processes, consistent with the hypothesis that aging is not under positive selection. However, within both mammals and primates, 95% of the promoters showed a positive correlation between increasing CpG density and species lifespan, and two thirds were shared between the primate subset and mammalian datasets. Thus, these genes may require greater buffering capacity against age-related dysregulation of DNA methylation in longer-lived species.


CpG: cytosine-phosphate-guanine; CGI: CpG Island; sDMRs: species-specific differentially methylated regions; PGLS: phylogenetic generalized least squares.