Revisiting the mouse mitochondrial DNA sequence

Abstract

The existence of reliable mtDNA reference sequences for each species is of great relevance in a variety of fields, from phylogenetic and population genetics studies to pathogenetic determination of mtDNA variants in humans or in animal models of mtDNA-linked diseases. We present compelling evidence for the existence of sequencing errors on the current mouse mtDNA reference sequence. This includes the deletion of a full codon in two genes, the substitution of one amino acid on five occasions and also the involvement of tRNA and rRNA genes. The conclusions are supported by: (i) the re-sequencing of the original cell line used by Bibb and Clayton, the LA9 cell line, (ii) the sequencing of a second L-derivative clone (L929), and (iii) the comparison with 12 other mtDNA sequences from live mice, 10 of them maternally related with the mouse from which the L cells were generated. Two of the latest sequences are reported for the first time in this study (Balb/cJ and C57BL/6J). In addition, we found that both the LA9 and L929 mtDNAs also contain private clone polymorphic variants that, at least in the case of L929, promote functional impairment of the oxidative phosphorylation system. Consequently, the mtDNA of the strain used for the mouse genome project (C57BL/6J) is proposed as the new standard for the mouse mtDNA sequence.

mtDNA phylogeny and evolution of laboratory mouse strains

“…Furthermore, the fact that, in the phylogenetic tree, common inbred strains appear clustered with the M. m. domesticus-derived strain, and far from representatives of other subspecies, shows that the common mitochon- Taking together our results and the history of inbred mice, it is likely that the same stocks of M. m. domesticus fancy mice were at the origin of all three groups; the maintenance of separate colonies in different regions would have resulted in the few differences that are now observed. The most divergent inbred strains were NZB and MilP as already reported by Bayona-Bafaluy et al (2003). Different reasons may explain the divergence of these two strains: the MilP strain is not a true common inbred strain, as it descends from a wild female mouse caught in Italy (Loveland et al 1990in Bayona-Bafaluy et al 2003, and NZB, although belonging to group B (Castle's mice), did not originate from Abbie Lathrop's stocks, but from unidentified "European & U.S. stocks," and it was outbred during its development (Beck et al 2000).…”

“…The most divergent inbred strains were NZB and MilP as already reported by Bayona-Bafaluy et al (2003). Different reasons may explain the divergence of these two strains: the MilP strain is not a true common inbred strain, as it descends from a wild female mouse caught in Italy (Loveland et al 1990in Bayona-Bafaluy et al 2003, and NZB, although belonging to group B (Castle's mice), did not originate from Abbie Lathrop's stocks, but from unidentified "European & U.S. stocks," and it was outbred during its development (Beck et al 2000).…”

“…No substitutions were observed in the control region. Insertions in transfer RNA genes were also observed in sites previously reported as highly polymorphic (Bayona-Bafaluy et al 2003; Supplemental Table 1). This similarity between common inbred strains has already been reported for some of these strains (Bayona-Bafaluy et al 2003).…”

“…Insertions in transfer RNA genes were also observed in sites previously reported as highly polymorphic (Bayona-Bafaluy et al 2003; Supplemental Table 1). This similarity between common inbred strains has already been reported for some of these strains (Bayona-Bafaluy et al 2003). However, we have extended the number of strains and included mice from different groups (Beck et al 2000): A (Swiss mice), B (Castle's mice), C (strains derived from China and Japan), and E (C57-related strains).…”

“…Little is known, however, of mitochondrial DNA (maternal) phylogenies of these strains. So far, there has been only one study on complete mtDNA sequences from different inbred strains, with the purpose of revising the complete mouse mtDNA reference sequence (Bayona-Bafaluy et al 2003). The study of mtDNA phylogenies has the potential to elucidate the matrilineal lineage of common inbred strains and its relationship to the main subspecific lineages.…”