The mitochondrial genome sequence of Mus terricolor: comparison with Mus musculus domesticus and implications for xenomitochondrial mouse modeling.

Knowledge of the mitochondrial DNA (mtDNA) sequence of divergent murine species is critical from both a phylogenetic perspective and in understanding nuclear-mitochondrial interactions, particularly as the latter influences our xenocybrid models of mitochondrial disease. To this end, the sequence of the mitochondrial genome of the murine species Mus terricolor (formerly Mus dunni) is reported and compared with the published sequence for the common laboratory mouse Mus musculus domesticus strain C57BL/6J. These species are of interest because xenomitochondrial cybrid mice were created that harbor M. terricolor mtDNA in a M. m. domesticus nuclear background. Although the total of 1763 nucleotide substitutions represents striking heterogeneity, the majority of these are silent, leading to highly conserved protein sequences with only 159 amino acid differences. Moreover, 58% of these amino acid differences represented conservative substitutions. All of the tRNA genes and rRNA genes have homology of 91% or greater. The control region shows the greatest heterogeneity, as expected, with 85% homology overall. Regions of 100% homology were found for Conserved Sequence Block I, Conserved Sequence Block III and the L-strand origin of replication. Complex I genes showed the greatest degree of difference among protein-coding genes with amino acid homology of 91-97% among the seven mitochondrial genes. Complexes III and IV genes show high homology ranging from 98-100%. From these data, complex I differences appear most critical for the viability of M. m. domesticus: M. terricolor cybrids. Moreover, the sequence information reported here should be useful in identifying critical regions for mitochondrial transfer between species, for furthering the understanding of mitochondrial dynamics and pathology in transmitochondrial organisms, and for the study of Mus genus origins.