Evolutionary adaptation revealed by comparative genome analysis of woolly mammoths and elephants

Comparative genomics studies typically limit their focus to single nucleotide variants (SNVs) and that was the case for previous comparisons of woolly mammoth genomes. We extended the analysis to systematically identify not only SNVs but also larger structural variants (SVs) and indels and found multiple mammoth-specific deletions and duplications affecting exons or even complete genes. The most prominent SV found was an amplification of RNase L (with different copy numbers in different mammoth genomes, up to 9-fold), involved in antiviral defense and inflammasome function. This amplification was accompanied by mutations affecting several domains of the protein including the active site and produced different sets of RNase L paralogs in four mammoth genomes likely contributing to adaptations to environmental threats. In addition to immunity and defense, we found many other unique genetic changes in woolly mammoths that suggest adaptations to life in harsh Arctic conditions, including variants involving lipid metabolism, circadian rhythms, and skeletal and body features. Together, these variants paint a complex picture of evolution of the mammoth species and may be relevant in the studies of their population history and extinction.