Biology subjects

Morgan, A. P.

Publications and source records attributed to Morgan, A. P..

8 recordsLinked to original sources

bioRxiv2025

Sex differences in crossover interference in house mice

Meiotic recombination ensures the fidelity of chromosome segregation in most organisms with sexual reproduction. The distribution of crossovers along chromosomes is governed in part by interference, which prevents multiple crossovers from occurring in close proximity, though not all crossovers are subject to interference. Neither the factors that control the strength of interference, nor the extent to which they vary within and between species, are well understood. Here I confirm that crossover interference is stronger in male than in female meiosis in house mice (Mus musculus), provide the first estimate of the proportion of non-interfering crossovers in female mice, and show that this proportion is lower than in males. Interference is stronger on shorter chromosomes in both sexes, but the frequency of non-interfering crossovers is similar across the range of chromosome size. Together with evidence that interference varies across strains and subspecies, my results provide a foundation for studying the evolution and sexual dimorphism in this important feature of meiosis in mice.

genetics↗

bioRxiv2024

Genetic background affects the strength of crossover interference in house mice

Meiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles from M. m. musculus tend to increase recombination rate, while inheriting a M. m. musculus X chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.

genetics↗

bioRxiv2022

Population structure and inbreeding in wild house mice (Mus musculus) at different geographic scales

House mice (Mus musculus) have spread globally as a result of their commensal relationship with humans. In the form of laboratory strains, both inbred and outbred, they are also among the most widely-used model organisms in biomedical research. Although the general outlines of house mouse dispersal and population structure are well known, details have been obscured by either limited sample size or small numbers of markers. Here we examine ancestry, population structure and inbreeding using SNP microarray genotypes in a cohort of 814 wild mice spanning five continents and all major subspecies of Mus, with a focus on M. m. domesticus. We find that the major axis of genetic variation in M. m. domesticus is a south-to-north gradient within Europe and the Mediterranean. The dominant ancestry component in North America, Australia, New Zealand and various small offshore islands is of northern European origin. Next we show that inbreeding is surprisingly pervasive and highly variable, even between nearby populations. By inspecting the length distribution of homozygous segments in individual genomes, we find that inbreeding in commensal populations is mostly due to consanguinity. Our results offer new insight into the natural history of an important model organism for medicine and evolutionary biology.

genetics↗

bioRxiv2019

Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

BackgroundTanzanias Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malarias persistence, but this paradigm has not been studied using modern genetic tools. MethodsWe used whole-genome sequencing (WGS) to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. We assessed ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections. ResultsWe identified significant decreases in the effective population sizes in both populations in the timeframe of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared large sections of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling,, we demonstrate a pair of isolates between the mainland and Zanzibar that are related at the expected level of half-siblings, consistent with recent importation ConclusionsThese findings suggest that importation plays an increasing role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.

genetics↗

bioRxiv2019

The Impact of Antimalarial Resistance on the Genetic Structure of Plasmodium falciparum in the DRC

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

genomics↗

bioRxiv2019

Instability of the pseudoautosomal boundary in house mice

Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa with dimorphic sex chromosomes, pairing between them in the heterogametic sex is limited to a narrow interval of residual sequence homology known as the pseudoautosomal region (PAR). Failure to form the obligate crossover in the PAR is associated with male infertility in house mice (Mus musculus) and humans. Yet despite this apparent functional constraint, the boundary and organization of the PAR is highly variable in mammals, and even between subspecies of mice. Here we estimate the genetic map in a previously-documented expansion of the PAR in the Mus musculus castaneus subspecies and show that the local recombination rate is 100-fold higher than the autosomal background. We identify an independent shift in the PAR boundary in the Mus musculus musculus subspecies and show that it involves a complex rearrangement but still recombines in heterozygous males. Finally, we demonstrate pervasive copy-number variation at the PAR boundary in wild populations of M. m. domesticus, M. m. musculus and M. m. castaneus. Our results suggest that the intensity of recombination activity in the PAR, coupled with relatively weak constraints on its sequence, permit the generation and maintenance in the population of unusual levels of polymorphism of unknown functional significance.

genetics↗

bioRxiv2018

Genetic characterization of invasive house mouse populations on small islands

House mice (Mus musculus) have dispersed to nearly every major landmass around the globe as a result of human activity. They are a highly successful invasive species, but their presence can be devastating for native ecosystems. This is particularly true on small offshore islands where mouse populations may grow unchecked by predators. Here we use genome-wide SNP genotypes to examine ancestry and population structure on two islands of ecological interest - Southeast Farallon Island, near San Francisco, CA; and Floreana Island in the Galapagos - in the context of a total cohort of 520 mice with diverse geographic origins, as a first step towards genetically-based eradication campaigns. We show that Farallon and Floreana mice, like those from previously-studied islands in both the Atlantic and Pacific Oceans, are of admixed European ancestry. We find that these populations are on average more inbred than mainland ones and passed through a strong colonization bottleneck with little subsequent genetic exchange. Finally we show that rodenticide resistance alleles present in parts of Europe are absent from all island populations studied. Our results add nuance to previous studies of island populations based on mitochondrial sequences or small numbers of microsatellites and will be useful for future eradication and monitoring efforts.

genetics↗

bioRxiv2016

Sequence and structural diversity of mouse Y chromosomes

Over the 180 million years since their origin, the sex chromosomes of mammals have evolved a gene repertoire highly specialized for function in the male germline. The mouse Y chromosome is unique among mammalian Y chromosomes characterized to date in that it is large, gene-rich and euchromatic. Yet little is known about its diversity in natural populations. Here we take advantage of published whole-genome sequencing data to survey the diversity of sequence and copy number of sex-linked genes in three subspecies of house mice. Copy number of genes on the repetitive long arm of both sex chromosomes is highly variable, but sequence diversity in non-repetitive regions is decreased relative to expectations based on autosomes. We use simulations and theory to show that this reduction in sex-linked diversity is incompatible with neutral demographic processes alone, but is consistent with recent positive selection on genes active during spermatogenesis. Our results support the hypothesis that the mouse sex chromosomes are engaged in ongoing intragenomic conflict.

genetics↗