mtDNA phylogeny and evolution of laboratory mouse strains

Abstract

Inbred mouse strains have been maintained for more than 100 years, and they are thought to be a mixture of four different mouse subspecies. Although genealogies have been established, female inbred mouse phylogenies remain unexplored. By a phylogenetic analysis of newly generated complete mitochondrial DNA sequence data in 16 strains, we show here that all common inbred strains descend from the same Mus musculus domesticus female wild ancestor, and suggest that they present a different mitochondrial evolutionary process than their wild relatives with a faster accumulation of replacement substitutions. Our data complement forthcoming results on resequencing of a group of priority strains, and they follow recent efforts of the Mouse Phenome Project to collect and make publicly available information on various strains.

Reply to letter from Felice L. Bedford and Doron Yacobi

“…This has been detected previously in mtDNA phylogeny (younger mutations are enriched in the first type, so that they often define branch tips) and a lot of debate on the selective pressures acting upon is ongoing [11][12][13][14][15][16] (and was also detected in animal models as our group has shown in lab mouse 17 ). The issue is, however, extraneous to the topic and goals of our paper; we can nevertheless clarify, as requested, that the finding does not result from a 'special clinical population of subjects'.…”

Increased mitochondrial mutation frequency after an island colonization: positive selection or accumulation of slightly deleterious mutations?

“…Because mouse inbred laboratory lines were also derived from only a single mitochondrial variant starting about 100 years ago [10], they can serve as an excellent comparison for the Kerguelen colonization. Among 57 completely sequenced genomes from laboratory lines, we found 30-point mutations (table 2), implying a mutation frequency of 3.2 Â 10 25 per nucleotide.…”

“…Hence, it seems safe to estimate an intermediate value 0.23 substitutions per site per Myr for recently separated wild populations of mice. The long-term evolutionary rate for the full mitochondrial genome, which is a combination of mutation rate and fixation rate, was estimated to be 0.037 substitutions per site per Myr [10], i.e. about six times lower than the short-term rate rsbl.royalsocietypublishing.org Biol Lett 9: 20121123 calculated above, which includes the slightly deleterious mutations that would be lost over time.…”

“…But it may be possible that generation times in the Kerguelen Archipelago populations have been longer than in most other mouse populations, owing to adverse climatic conditions. If we take the laboratory line rate, which was estimated to have had 2.4 generations per year [10], we would get 0.32 substitutions per site per Myr. Hence, it seems safe to estimate an intermediate value 0.23 substitutions per site per Myr for recently separated wild populations of mice.…”

“…Mitochondrial genomes from inbred laboratory lines were retrieved from GenBank (accession nos in electronic supplementary material, table S2). Since both the island mice and the laboratory mice are derived from a single, albeit different, mitochondrial haplotype [7,10], we estimated mutation frequencies with respect to the total number of nucleotides sequenced by counting the mutations in comparison to the consensus sequence, in a procedure analogous to the estimation of mutation frequencies from mutation-accumulation lines [8].…”