Biology subjects

Dumont, B. L.

Publications and source records attributed to Dumont, B. L..

3 recordsLinked to original sources

bioRxiv2021

Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X-and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action. ARTICLE SUMMARYWe compiled breeding records from The Collaborative Cross (CC) mouse mapping population to quantify the frequency and explore potential mechanisms of sex ratio distortion. Strikingly, more than one-third of CC strains yield significantly sex-biased litters. These sex biases are not mediated by environmental effects and are moderately heritable. We conclude that the widespread sex ratio distortion in the CC manifests from multilocus permutations of selfish sex-linked elements and suppressors that are only recovered in the recombinant CC strains.

genetics↗

bioRxiv2021

Selection shapes the landscape of functional variation in wild house mice

BackgroundThrough human-aided dispersal, house mice have recently colonized new and diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premiere mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. ResultsHere, we leveraged 154 whole-genome sequences from diverse wild house mouse populations, subspecies, and species to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at numerous genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. ConclusionsOverall, our findings underscore the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work highlights the biomedical relevance of wild mouse genetic diversity and unsdercores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.

evolutionary biology↗

bioRxiv2020

Population and species diversity at mouse centromere satellites

Centromeres are satellite-rich chromatin domains that are essential for chromosome segregation. Centromere satellites evolve rapidly between species but little is known about population-level diversity across these loci. We developed a k-mer based method to quantify centromere copy number and sequence variation from whole genome sequencing data. We applied this method to diverse inbred and wild house mouse (genus Mus) genomes and uncover pronounced variation in centromere architecture between strains and populations. We show that patterns of centromere diversity do not mirror the known ancestry of inbred strains, revealing a remarkably rapid rate of centromere sequence evolution. We document increased satellite homogeneity and copy number in inbred compared to wild mice, suggesting that inbreeding remodels mouse centromere architecture. Our results highlight the power of k-mer based approaches for probing variation across repetitive regions and provide the first in-depth, phylogenetic portrait of centromere variation across Mus musculus.

genomics↗