Epigenetic clocks provide novel tools for inferring demographic trends in free-ranging populations: a case study in three large mammals

Background/Question/Methods

Epigenetic modifications such as DNA methylation (DNAm) can impact phenotypes via altering gene expression without changing the DNA sequence. DNAm is a chemical alteration that involves the transfer of a methyl group to a cytosine base, mostly occurring on CpG sites (cytosine followed by guanine). Some regions of the genome, called CpG islands (CGI), contain a high frequency of CpG, and are known to overlap the majority of gene promoter regions in mammals, being evolutionarily important as they have been highly conserved across vertebrates. The rate of DNAm, particularly hypermethylation, on specific CpG sites changes over the course of an individual’s lifetime, making it possible to age samples based on their methylation levels. Moreover, traits like longevity and body size appear correlated to DNAm. Here we applied a large-scale methylation array (~40,000 CpGs) to black bear, white-tailed deer, and mountain goats. Using unsupervised machine learning we built epigenetic clocks that are highly predictive of chronological age.

Results/Conclusions

Understanding the age structure of natural population is fundamental to wildlife management. Estimating the age of wildlife at the scale of most jurisdictions is impossible awith contemporary methods. Common methods based off teeth or other features like horn annuli are challenging and error prone. Here we report highly predictive (r > 0.90) epigenetic clocks for black bear, white-tailed deer and mountain goat. The species-specific clocks are built from a handful, approximately 20 CpG sites per species, making customized, cost-effective aging assays a reality for wildlife. We report the development of species-specific assays that can reliably age and sex species at scale, which has the potential to revolutionize non-invasive and DNA mark-recapture studies.