Fine-scale phylogenetic discordance across the house mouse genome

Abstract

Population genetic theory predicts discordance in the true phylogeny of different genomic regions when studying recently diverged species. Despite this expectation, genome-wide discordance in young species groups has rarely been statistically quantified. The house mouse subspecies group provides a model system for examining phylogenetic discordance. House mouse subspecies are recently derived, suggesting that even if there has been a simple tree-like population history, gene trees could disagree with the population history due to incomplete lineage sorting. Subspecies of house mice also hybridize in nature, raising the possibility that recent introgression might lead to additional phylogenetic discordance. Single-locus approaches have revealed support for conflicting topologies, resulting in a subspecies tree often summarized as a polytomy. To analyze phylogenetic histories on a genomic scale, we applied a recently developed method, Bayesian concordance analysis, to dense SNP data from three closely related subspecies of house mice: Mus musculus musculus, M. m. castaneus, and M. m. domesticus. We documented substantial variation in phylogenetic history across the genome. Although each of the three possible topologies was strongly supported by a large number of loci, there was statistical evidence for a primary phylogenetic history in which M. m. musculus and M. m. castaneus are sister subspecies. These results underscore the importance of measuring phylogenetic discordance in other recently diverged groups using methods such as Bayesian concordance analysis, which are designed for this purpose.

Figure 1. Three possible phylogenetic histories.

The three possible phylogenetic relationships among subspecies of house mice are shown, rooted by rat.

Figure 2. Fine-scale phylogenetic discordance.

The posterior probability of each topology is mapped along chromosome 19 to characterize fine-scale patterns of discordance among the 410 loci. Many regions of the chromosome rapidly switch between phylogenetic histories and are characterized by loci that have a high posterior probability for a single topology. Colors correspond to the three topologies.

Figure 3. Genome-wide phylogenetic discordance.

Bayesian concordance factors were calculated from the posterior probability distributions of 14,081 single-locus phylogenetic analyses. The concordance analysis is depicted using three different priors on gene tree concordance: complete independence among loci (α  =  infinity), a high probability of concordance among loci (α = 10⁻⁶), and an intermediate level of concordance (α = 1). The M. m. musculus/M. m. castaneus topology is supported by significantly more loci than the other two topologies regardless of the prior on gene tree concordance. Colors correspond to the three topologies. Error bars are 95% credibility intervals.

Figure 4. Phylogenetic discordance between the autosomes and the X chromosome.

Significantly less discordance is observed across loci of the X chromosome (X: 442 loci) than the autosomes (A: 13,639 loci). This is shown by significantly higher support for the primary phylogenetic history, the M. m. musculus/M. m. castaneus topology, at the expense of loci supporting the other two topologies. Colors correspond to the three topologies. Error bars are 95% credibility intervals.

Figure 5. Simulated ascertainment bias against M. m. castaneus.

Varying proportions of M. m. castaneus specific SNPs were removed from chromosomes 18 and 19 to simulate increased ascertainment bias against this taxon. The difference in concordance factors between M. m. musculus/M. m. castaneus and M. m. castaneus/M. m. domesticus do not significantly differ at all levels of artificial bias. This indicates that recovery of a M. m. musculus/M. m. castaneus primary phylogenetic history is robust to increased ascertainment bias. Colors correspond to the three topologies. Error bars are 95% confidence intervals.

Figure 6. Sliding window analysis of discordance across the X chromosome.

Discordance within a four-locus sliding window was calculated across the X chromosome and is plotted as the midpoint position of each window. The M. m. musculus/M. m. castaneus topology (red) shows significantly higher regions along the X chromosome where known hybrid male sterility loci are mapped (Hstx1) . The M. m. musculus/M. m. domesticus topology (blue) decreases within these regions. The entire Hstx1 interval is indicated by the purple line, whereas the peak of this quantitative trait locus is indicated by the orange line. The black line indicates the chromosome-wide concordance factor for the M. m. musculus/M. m. castaneus topology (0.450).