Connecting DNA Repair Genes with Genome Divergence through Base Composition at Polymorphic Sites

DNA base composition is a fundamental genome feature. However, the evolutionary pattern of base composition and its potential causes have not been well understood. Leveraging the wealth of genome sequences, we characterized composition of nucleotides along the same DNA strand, which is the way sequence was stored and displayed in GenBank, from different levels. Two consistent patterns were discovered. Base composition follows the individual-strand base equality rule at the genome, chromosome and polymorphic site levels. More intriguingly, clear separation of basal and derived groups by Base Composition across SNPs (BCS) was consistently observed across multiple species, suggesting common underlying mechanisms. With BCS as a phenotype, genome scans with Human 1000 Genomes and HapMap3 data identified a set of significant genomic regions enriched with Gene Ontology terms for DNA repair. For three DNA repair genes (BRIP1, PMS2P3 and TTDN), ENCODE data provided evidence for interaction between genomic regions containing these genes and regions containing the significant SNPs. Our findings provide insights into the mechanisms of genome evolution.