Divergent genome evolution caused by regional variation in DNA gain and loss between human and mouse

摘要

Author summary Approximately 2% of a mammalian genome is protein-coding DNA, the remainder is non-coding DNA. In mammals, this non-coding DNA fraction has undergone large amounts of turnover since placental mammals diverged from a common ancestor. For example, human and mouse, two species who diverged approximately 100 million years ago, share only approximately 40% of their DNA sequence. Given that genome size has remained relatively constant since their divergence, this low level of ancestral DNA suggests there has been large amounts of DNA gain and loss in both lineages. To understand the cause and evolutionary impact of DNA gain and loss in mammalian genomes, we developed novel techniques that mapped individual DNA gain and loss events across distantly related species. By tallying the amount of DNA gained and lost across genomic regions we were able to measure its association with various genomic features. Our results showed that DNA loss in human and mouse mainly occurs in gene-rich open chromatin regions. In contrast DNA gain was mainly driven by transposition. In each lineage the proportion of total gain could be assigned to distinct transposon types. This meant that based on the differential activity of specific transposon types region-specific gain was following lineage-specific accumulation patterns, ultimately leading to divergent genome evolution. In addition, we measured how genes in DNA gain and loss hotspots associated with particular biological processes. Perhaps most strikingly, we found that mouse DNA loss hotspots overlapped highly conserved regions containing genes involved in development. This suggests that while the genomic environment in these regions is prone to DNA loss events, those that interrupt regulatory elements are strongly selected against.