ORCID Profile
0000-0002-1853-7469
Current Organisations
University of Sheffield
,
Karlstad University
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Publisher: Proceedings of the National Academy of Sciences
Date: 18-02-2021
Abstract: Sex chromosomes are not only involved in genetic sex determination—they are also important factors in sexual conflict and speciation. Using laboratory experiments and population genetic modeling, we show that the sex chromosomes of Drosophila melanogaster can coevolve antagonistically. We found that swapping sex chromosomes between five D. melanogaster populations increased male fitness, apparently at the cost of reduced offspring survival. After 25 generations, these fitness effects had disappeared, consistent with the resolution of conflict after disrupting antagonistically coevolved X- and Y-linked genes. Our population genetic models show that antagonistic coevolution between sex chromosomes is a biologically plausible explanation for our empirical findings. Together, our empirical and theoretical results provide support for a potential path to speciation through sexual conflict.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-05-2011
Abstract: Polymorphisms in the organelle genome have little effect in female flies but do alter gene expression in males.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.CUB.2015.09.012
Abstract: Mitochondria underpin energy conversion in eukaryotes. Their small genomes have been the subject of increasing attention, and there is evidence that mitochondrial genetic variation can affect evolutionary trajectories and shape the expression of life-history traits considered to be key human health indicators [1, 2]. However, it is not understood how genetic variation across a diminutive genome, which in most species harbors only about a dozen protein-coding genes, can exert broad-scale effects on the organismal phenotype [2, 3]. Such effects are particularly puzzling given that the mitochondrial genes involved are under strong evolutionary constraint and that mitochondrial gene expression is highly conserved across erse taxa [4]. We used replicated genetic lines in the fruit fly, Drosophila melanogaster, each characterized by a distinct and naturally occurring mitochondrial haplotype placed alongside an isogenic nuclear background. We demonstrate that sequence variation within the mitochondrial DNA (mtDNA) affects both the copy number of mitochondrial genomes and patterns of gene expression across key mitochondrial protein-coding genes. In several cases, haplotype-mediated patterns of gene expression were gene-specific, even for genes from within the same transcriptional units. This invokes post-transcriptional processing of RNA in the regulation of mitochondrial genetic effects on organismal phenotypes. Notably, the haplotype-mediated effects on gene expression could be traced backward to the level of in idual nucleotides and forward to sex-specific effects on fertility and longevity. Our study thus elucidates how small-scale sequence changes in the mitochondrial genome can achieve broad-scale regulation of health-related phenotypes and even contribute to sex-related differences in longevity.
Publisher: Oxford University Press (OUP)
Date: 11-05-2018
Abstract: Mitochondrial replacement, a form of nuclear transfer, has been proposed as a germline therapy to prevent the transmission of mitochondrial diseases. Mitochondrial replacement therapy has been licensed for clinical application in the UK, and already carried out in other countries, but little is known about negative or unintended effects on the health of offspring born using this technique. Studies in invertebrate models have used techniques that achieve mitochondrial replacement to create offspring with novel combinations of mitochondrial and nuclear genotype. These have demonstrated that the creation of novel mitochondrial-nuclear interactions can lead to alterations in offspring characteristics, such as development rates, fertility and longevity. However, it is currently unclear whether such interactions could similarly affect the outcomes of vertebrate biomedical studies, which have sought to assess the efficacy of the replacement therapy. This systematic review addresses whether the effects of mitochondrial replacement on offspring characteristics differ in magnitude between biological (conducted on invertebrate models, with an ecological or evolutionary focus) and biomedical studies (conducted on vertebrate models, with a clinical focus). Studies were selected based on a key-word search in 'Web of Science', complemented by backward searches of reviews on the topic of mitochondrial-nuclear (mito-nuclear) interactions. In total, 43 of the resulting 116 publications identified in the search contained reliable data to estimate effect sizes of mitochondrial replacement. We found no evidence of publication bias when examining effect-size estimates across s le sizes. Mitochondrial replacement consistently altered the phenotype, with significant effects at several levels of organismal performance and health, including gene expression, anatomy, metabolism and life-history. Biomedical and biological studies, while differing in the methods used to achieve mitochondrial replacement, showed only marginally significant differences in effect-size estimates (-0.233 [CI: -0.495 to -0.011]), with larger effect-size estimates in biomedical studies (0.697 [CI: 0.450-0.956]) than biological studies (0.462 [CI: 0.287-0.688]). Humans showed stronger effects than other species. Effects of mitochondrial replacement were also stronger in species with a higher basal metabolic rate. Based on our results, we conducted the first formal risk analysis of mitochondrial replacement, and conservatively estimate negative effects in at least one in every 130 resulting offspring born to the therapy. Our findings suggest that mitochondrial replacement may routinely affect offspring characteristics across a wide array of animal species, and that such effects are likely to extend to humans. Studies in invertebrate models have confirmed mito-nuclear interactions as the underpinning cause of organismal effects following mitochondrial replacement. This therefore suggests that mito-nuclear interactions are also likely to be contributing to effects seen in biomedical studies, on vertebrate models, whose effect sizes exceeded those of biological studies. Our results advocate the use of safeguards that could offset any negative effects (defining any unintended effect as being negative) mediated by mito-nuclear interactions following mitochondrial replacement in humans, such as mitochondrial genetic matching between donor and recipient. Our results also suggest that further research into the molecular nature of mito-nuclear interactions would be beneficial in refining the clinical application of mitochondrial replacement, and in establishing what degree of variation between donor and patient mitochondrial DNA haplotypes is acceptable to ensure 'haplotype matching'.
Publisher: Cold Spring Harbor Laboratory
Date: 25-10-2019
DOI: 10.1101/818146
Abstract: Antagonistic interactions between the sexes are important drivers of evolutionary ergence. Interlocus sexual conflict is generally described as a conflict between alleles at two interacting loci whose identity and genomic location are arbitrary. Here we build on previous theory and suggest that when these two loci are located on the sex chromosomes it can lead to cycles of antagonistic coevolution between them, and therefore between the sexes. We tested this hypothesis by performing experimental crosses using Drosophila melanogaster in which we reciprocally exchanged the sex chromosomes between five wild-type populations in a round-robin design. Disrupting putatively coevolved sex chromosome pairs resulted in increased male reproductive success in 16 out of 20 experimental populations (10 of which were significant), but also resulted in lower offspring egg-to-adult viability that affected both male and female fitness. After 25 generations of experimental evolution these sexually antagonistic fitness effects appeared to have been resolved. To help formalise our hypothesis, we developed population genetic models of antagonistic coevolution using fitness expressions based on our empirical results. Our models support the conclusion that antagonistic coevolution between the sex chromosomes is plausible under the fitness effects observed in our experiments. Together, our results lend both empirical and theoretical support to the idea that a cycle of antagonistic coevolution can occur between sex chromosomes and illustrates how this process may drive genetic and phenotypic ergence between populations. Sex chromosomes are not only involved in genetic sex determination – they are also important factors in sexual conflict and speciation. Here, using a combination of experiments and population genetic models, we show that the sex chromosomes in Drosophila melanogaster can coevolve antagonistically. We found that swapping sex chromosomes between five Drosophila melanogaster populations increased male fitness at the cost of reduced offspring survival. After 25 generations, the increase had disappeared, consistent with the completion of a cycle of antagonistic coevolution. Using parameter values based on these empirical data, our models show that antagonistic coevolution between the sex chromosomes is a biologically plausible explanation for the results. Thus, our results point to a potentially important path to speciation through sexual conflict.
Publisher: The Royal Society
Date: 17-01-2018
Abstract: Strict maternal inheritance renders the mitochondrial genome susceptible to accumulating mutations that harm males, but are otherwise benign or beneficial for females. This ‘mother's curse’ effect can degrade male survival and fertility if unopposed by counteracting evolutionary processes. Coadaptation between nuclear and mitochondrial genomes—with nuclear genes evolving to compensate for male-harming mitochondrial substitutions—may ultimately resolve mother's curse. However, males are still expected to incur a transient fitness cost during mito-nuclear coevolution, and it remains unclear how severe such costs should be. We present a population genetic analysis of mito-nuclear coadaptation to resolve mother's curse effects, and show that the magnitude of the ‘male mitochondrial load’—the negative impact of mitochondrial substitutions on male fitness components—may be large, even when genetic variation for compensatory evolution is abundant. We also find that the male load is surprisingly sensitive to population size: male fitness costs of mito-nuclear coevolution are particularly pronounced in both small and large populations, and minimized in populations of intermediate size. Our results reveal complex interactions between demography and genetic constraints during the resolution of mother's curse, suggesting potentially widespread species differences in susceptibility to mother's curse effects.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-09-2013
Abstract: Mitochondrial replacement therapy might bear health risks, especially for males.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Edward Morrow.