Biology subjects

Kopania, E. E. K.

Publications and source records attributed to Kopania, E. E. K..

9 recordsLinked to original sources

bioRxiv2026

RERconverge Update: Runtime Reduction and Analysis Function Overhaul

MotivationConvergent evolution, or the independent acquisition of similar phenotypes in distinct lineages, provides a powerful framework for investigating genomic changes associated with a phenotype. This paper details an update to RERconverge, a powerful R package that tests for associations between gene relative evolutionary rates (RERs) and convergent phenotypes to infer genomic regions associated with traits or selective pressures. We introduce new customizable analysis choices and scalable and efficient algorithms that can process larger genomic datasets, a critical improvement as genomic data become available for more species. ResultsModifications to core functions in the RERconverge pipeline resulted in an immense speedup (by a factor of up to 28.6). The function that tests for associations between phenotypes and RERs has been expanded to include two new analytical methods for outlier control; we also provide here a summary of the statistical tests users can perform, along with their use cases. Availability and implementationThe code and walkthrough vignettes for the package are available at https://github.com/nclark-lab/RERconverge. ContactNathan L. Clark nclark@pitt.edu; Maria Chikina mchikina@pitt.edu

genomics↗

bioRxiv2024

Mammalian retinal specializations for high acuity vision evolve in response to both foraging strategies and morphological constraints

Vision is a complex sensory system that requires coordination among cellular and morphological traits, and it remains unclear how functional relationships among traits interact with ecological selective pressures to shape the evolution of vision. Many species have specialized high visual acuity regions in the retina defined by patterns of ganglion cell density, which may evolve in response to ecological conditions. For example, ganglion cell density can increase radially towards the center of the retina to form an area centralis, which is thought to improve acuity towards the center of the visual field in predators. Another example is the horizontal streak, where ganglion cells are dense across the center of the retina, which is thought to be beneficial in horizon-dominated habitats. At the morphological level, many have proposed that predation selects for high orbit convergence angles, or forward-facing eyes. We tested these hypotheses in a phylogenetic framework across eutherian mammals and only found support for the association between the horizontal streak and horizon-dominated habitats. We also tested if retinal specializations evolve in response to orbit convergence angles. We found that horizontal streaks were associated with side-facing eyes, which may both facilitate panoramic vision. Previous studies observed that some species with side-facing eyes have an area centralis shifted towards the temporal side of the retina, such that the high acuity region would project forward, but this relationship had not been tested quantitatively. We found that the temporal distance of the area centralis from the center of the retina was inversely correlated with orbit convergence, as predicted. Our work shows a strong relationship between orbit convergence and retinal specializations. We find support that both visual ecology and functional interactions among traits play important roles in the evolution of some ocular traits across mammals.

evolutionary biology↗

bioRxiv2023

Molecular evolution of male reproduction across species with highly divergent sperm morphology in diverse murine rodents

It remains unclear how variation in the intensity of sperm competition shapes phenotypic and molecular evolution across clades. Mice and rats in the subfamily Murinae are a rapid radiation exhibiting incredible diversity in sperm morphology and production. We combined phenotypic and genomic data to perform phylogenetic comparisons of male reproductive traits and genes across 78 murine species. We identified several shifts towards smaller relative testes mass, presumably reflecting reduced sperm competition. Several sperm traits were associated with relative testes mass, suggesting that mating system evolution selects for convergent suites of traits related to sperm competitive ability. We predicted that sperm competition would also drive more rapid molecular divergence in species with large testes. Contrary to this, we found that many spermatogenesis genes evolved more rapidly in species with smaller relative testes mass due to relaxed purifying selection. While some reproductive genes evolved rapidly under recurrent positive selection, relaxed selection played a greater role in underlying rapid evolution in small testes species. Our work demonstrates that postcopulatory sexual selection can impose strong purifying selection shaping the evolution of male reproduction, and that broad patterns of molecular evolution may help identify genes that contribute to male fertility.

evolutionary biology↗

bioRxiv2022

The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice

Incompatibilities on the sex chromosomes are important in the evolution of hybrid male sterility, but the evolutionary forces underlying this phenomenon are unclear. House mice (Mus musculus) lineages have provided powerful models for understanding the genetic basis of hybrid male sterility. X chromosome-autosome interactions cause strong incompatibilities in Mus musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. Additionally, XY chromosome conflict has resulted in rapid expansions of ampliconic genes with dosage-dependent expression that is essential to spermatogenesis. Here we evaluated the contribution of XY lineage mismatch to male fertility and stage-specific gene expression in hybrid mice. We performed backcrosses between two house mouse subspecies to generate reciprocal Y-introgression strains and used these strains to test the effects of XY mismatch in hybrids. Our transcriptome analyses of sorted spermatid cells revealed widespread overexpression of the X chromosome in sterile F1 hybrids independent of Y chromosome subspecies origin. Thus, postmeiotic overexpression of the X chromosome in sterile F1 mouse hybrids is likely a downstream consequence of disrupted meiotic X-inactivation rather than XY gene copy number imbalance. Y-chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise nonhybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of XY conflict. Collectively, these findings suggest that rapid sex chromosome gene family evolution driven by genomic conflict has not resulted in strong male reproductive barriers between these subspecies of house mice.

evolutionary biology↗

bioRxiv2021

The evolution of widespread recombination suppression on the Dwarf Hamster (Phodopus) X chromosome

The mammalian X chromosome shows strong conservation among distantly related species, limiting insights into the distinct selective processes that have shaped sex chromosome evolution. We constructed a chromosome-scale de novo genome assembly for the Siberian dwarf hamster (Phodopus sungorus), a species reported to show extensive recombination suppression across an entire arm of the X chromosome. Combining a physical genome assembly based on shotgun and long-range proximity ligation sequencing with a dense genetic map, we detected widespread suppression of female recombination across [~]65% of the Phodopus X chromosome. This region of suppressed recombination likely corresponds to the Xp arm, which has previously been shown to be highly heterochromatic. Using additional sequencing data from two closely-related species (P. campbelli and P. roborovskii), we show that recombination suppression on Xp appears to be independent of major structural rearrangements. The suppressed Xp arm was enriched for several transposable element families and de-enriched for genes primarily expressed in the placenta, but otherwise showed similar gene densities, expression patterns, and rates of molecular evolution when compared to the recombinant Xq arm. Phodopus Xp gene content and order was also broadly conserved relative to the more distantly related rat X chromosome. Collectively, these data suggest that widespread suppression of recombination has likely evolved through the transient induction of facultative heterochromatin on the Phodopus Xp arm without major changes in chromosome structure or genetic content. Thus, dramatic changes in the recombination landscape have so far had relatively subtle influences on overall patterns of X-linked molecular evolution. Significance StatementSex chromosome evolution represents a dynamic process of genomic specialization that is thought to be dependent on evolution of recombination. Here we use genome sequencing and genetic mapping to show that one arm comprising the majority of the X chromosome in a species of dwarf hamster has largely lost the ability to recombine in males and females. Although these dramatic shifts in recombination frequencies might eventually lead to sex chromosome degeneration, loss of recombination on this arm is associated with relatively minor changes in chromosome structure and gene contents in this species. These results underscore the conservation of the X chromosome across mammals, and allow us to test predictions about how genetic recombination influences sex chromosome evolution.

genomics↗

bioRxiv2021

Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids

Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of Meiotic Sex Chromosome Inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes awaits further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.

evolutionary biology↗

bioRxiv2021

Molecular Evolution across Mouse Spermatogenesis

Genes involved in spermatogenesis tend to evolve rapidly, but we still lack a clear understanding of how different components of molecular evolution vary across this complex developmental process. We used fluorescence activated cell sorting (FACS) to generate expression data for both early (meiotic) and late (postmeiotic) cell types across thirteen inbred strains of mice (Mus) spanning ~7 million years of evolution. We used these comparative developmental data to investigate the evolution of lineage-specific expression, protein-coding sequences, and expression levels. We found increased lineage specificity and more rapid protein-coding and expression divergence during late spermatogenesis, suggesting that signatures of rapid testis molecular evolution are punctuated across sperm development. Despite strong overall developmental parallels in these components of molecular evolution, protein and expression divergences were only weakly correlated across genes. We detected more rapid protein evolution on the X chromosome relative to the autosomes, while X-linked gene expression tended to be relatively more conserved likely reflecting chromosome-wide regulatory constraints. Using allele-specific FACS expression data from crosses between four strains, we found that the relative contributions of different regulatory mechanisms also differed between cell-types. Genes showing cis-regulatory changes were more common late in spermatogenesis, and tended to be associated with larger differences in expression levels and greater expression divergence between species. In contrast, genes with trans-acting changes were more common early and tended to be more conserved across species. Our findings advance understanding of gene evolution across spermatogenesis and underscore the fundamental importance of developmental context in molecular evolutionary studies.

evolutionary biology↗

bioRxiv2018

Automated nuclear cartography reveals conserved sperm chromosome territory localization across 2 million years of mouse evolution

Measurements of nuclear organization in asymmetric nuclei in 2D images have traditionally been manual. This is exemplified by attempts to measure chromosome position in sperm samples, typically by dividing the nucleus into zones, and manually scoring which zone a FISH signal lies in. This is time consuming, limiting the number of nuclei that can be analyzed, and prone to subjectivity. We have developed a new approach for automated mapping of FISH signals in asymmetric nuclei, integrated into an existing image analysis tool for nuclear morphology. Automatic landmark detection defines equivalent structural regions in each nucleus, then dynamic warping of the FISH images to a common shape allows us to generate a composite of the signal within the entire cell population. Using this approach, we mapped the positions of the sex chromosomes and two autosomes in three mouse lineages (Mus musculus domesticus, Mus musculus musculus and Mus spretus). We found that in all three, chromosomes 11 and 19 tend to interact with each other, but are shielded from interactions with the sex chromosomes. This organization is conserved across 2 million years of mouse evolution.

genomics↗

bioRxiv2018

A high-throughput method for unbiased quantitation and categorisation of nuclear morphology

The physical arrangement of chromatin in the nucleus is cell type and species specific. This is particularly evident in sperm, in which most of the cytoplasm has been lost; the shape of the nucleus reflects the shape of the cell. Mice have distinctive falciform ( hook shaped) sperm heads and nuclei. Quantification of the differences in shape variation between mouse species and lines often relies on manual measurement and classification that leads to subjective results, making comparisons within and between samples difficult.\n\nWe have developed an analysis program for assessing the morphology of asymmetric nuclei, and characterised the sperm of mice from a range of inbred, outbred and wild-derived mouse lines. We find that laboratory lines have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred lines, and that sperm shape in the F1 offspring of CBA and C57Bl6J lines is subtly affected by the direction of the cross.\n\nHierarchical clustering can distinguish distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors. We quantified the range of morphological defects in the inbred BALB/c line, demonstrating we can identify different morphological subgroups. This approach has applications for studies of sperm development, infertility and toxicology.

genomics↗