Evolution of a record-setting AT-rich genome: indel mutation, recombination, and substitution bias.

Genome-wide nucleotide composition varies widely among species. Despite extensive research, the source of genome-wide nucleotide composition diversity remains elusive. Yeast mitochondrial genomes (mitogenomes) are highly A+T rich, and they provide a unique opportunity to study the evolution of AT-biased landscape. In this study, we sequenced ten complete mitogenomes of the Saccharomycodes ludwigii yeast with 8% G+C content, the lowest genome-wide %(G+C) in all published genomes to date. The Saccharomycodes ludwigii mitogenomes have high densities of short tandem repeats but severely underrepresented mononucleotide repeats. Comparative population genomics of these record-setting A+T rich genomes show dynamic indel mutations and strong mutation bias towards A/T. Indel mutations play a greater role in genomic variation among very closely related strains than nucleotide substitutions. Indels have resulted in presence-absence polymorphism of tRNAArg (ACG) among Saccharomycodes ludwigii mitogenomes. Interestingly, these mitogenomes have undergone recombination, a genetic process that can increase G+C content by GC-biased gene conversion. Finally, the expected equilibrium G+C content under mutation pressure alone is higher than observed G+C content, suggesting existence of mechanisms other than AT-biased mutation operating to increase A/T. Together, our findings shed new lights on mechanisms driving extremely AT-rich genomes.