Biology subjects

Edward H Morrow

Publications and source records attributed to Edward H Morrow.

6 recordsLinked to original sources

bioRxiv2016

Sexual dimorphism in the Drosophila metabolome increases throughout development

The expression of sexually dimorphic phenotypes from a shared genome between males and females is a longstanding puzzle in evolutionary biology. Increasingly, research has made use of transcriptomic technology to examine the molecular basis of sexual dimorphism through gene expression studies, but even this level of detail misses the metabolic processes that ultimately link gene expression with the whole organism phenotype. We use metabolic profiling in Drosophila melanogaster to complete this missing step, with a view to examining variation in male and female metabolic profiles, or metabolomes, throughout development. We show that the metabolome varies considerably throughout larval, pupal and adult stages. We also find significant sexual dimorphism in the metabolome, although only in pupae and adults, and the extent of dimorphism tends to increase throughout development. We compare this to transcriptomic data from the same population and find that the general pattern of increasing sex differences throughout development is mirrored in RNA expression. We discuss our results in terms of the usefulness of metabolic profiling in linking genotype and phenotype to more fully understand the basis of sexually dimorphic phenotypes.

Physiology↗

bioRxiv2016

Sex-biased gene expression in Drosophila melanogaster is constrained by ontogeny and genetic architecture

Sexual dimorphism is predicted to be constrained by the underlying genetic architecture shared between the sexes and through ontogeny, but whole-transcriptome data for both sexes across genotypes and developmental stages are lacking. Within a quantitative genetic framework, we sequenced RNA from Drosophila melanogaster at different developmental stages to examine sex-biased gene expression and how selection acts upon it. We found evidence that gene expression is constrained by both univariate and multivariate shared genetic variation between genes, sexes and developmental stages, but may be resolved by differential splicing. These results provide a comprehensive picture of how conflict over sexual dimorphism varies through development and clarifies the conditions under which it is predicted to evolve.

Genetics↗

bioRxiv2015

Rapid evolution of the inter-sexual genetic correlation for fitness in Drosophila melanogaster

Sexual antagonism (SA) arises when male and female phenotypes are under opposing selection, yet genetically correlated. Until resolved, antagonism limits evolution towards optimal sex-specific phenotypes. Despite its importance for sex-specific adaptation and existing theory, the dynamics of SA resolution are not well understood empirically. Here, we present data from Drosophila melanogaster, compatible with a resolution of SA. We compared two independent replicates of the LHM population in which SA had previously been described. Both had been maintained under identical, controlled conditions, and separated for <250 generations. Although heritabilities of male and female fitness were similar, the inter-sexual genetic correlation differed significantly, being negative in one replicate (indicating SA) but close to zero in the other. Using population sequencing, we show that phenotypic differences were associated with population divergence in allele frequencies at non-random loci across the genome. Large frequency changes were more prevalent in the population without SA and were enriched at loci mapping to genes previously shown to have a sexually antagonistic relationships between expression and fitness. Our data suggest that rapid evolution towards SA resolution has occurred in one of the populations and open avenues towards studying the genetics of SA and its resolution.

Evolutionary Biology↗

bioRxiv2015

Risks inherent to mitochondrial replacement

The UK Government has recently been debating whether or not to legislate to allow mitochondrial replacement (MR) to be used in the clinic. However, we are concerned that some of the science of MR has been misunderstood, or otherwise given only fleeting consideration. We set out our arguments below and offer a way forward to ensure that MR can safely deliver the health benefits it promises for those suffering from mitochondrial-related diseases\n\nRecent innovations that enable mitochondrial DNA (mtDNA) mutations to be eliminated from the germline, by replacing mutated mitochondria within an oocyte with mitochondria from a healthy donor female1-3, offer hope for the eradication of several debilitating and lethal mitochondrial diseases. The potential for clinical application of MR has received widespread support4,5, but has also provoked safety and ethical concerns from the public ...

Evolutionary Biology↗

bioRxiv2013

The evolution of sex differences in disease genetics

There are significant differences in the biology of males and females, ranging from biochemical pathways to behavioural responses, which are relevant to modern medicine. Broad-sense heritability estimates differ between the sexes for many common medical disorders, indicating that genetic architecture can be sex-dependent. Recent genome-wide association studies (GWAS) have successfully identified sex-specific and sex-biased effects, where in addition to sex-specific effects on gene expression, twenty-two medical traits have sex-specific or sex-biased loci. Sex-specific genetic architecture of complex traits is also extensively documented in model organisms using genome-wide linkage or association mapping, and in gene disruption studies. The evolutionary origins of sex-specific genetic architecture and sexual dimorphism lie in the fact that males and females share most of their genetic variation yet experience different selection pressures. At the extreme is sexual antagonism, where selection on an allele acts in opposite directions between the sexes. Sexual antagonism has been repeatedly identified via a number of experimental methods in a range of different taxa. Although the molecular basis remains to be identified, mathematical models predict the maintenance of deleterious variants that experience selection in a sex-dependent manner. There are multiple mechanisms by which sexual antagonism and alleles under sex-differential selection could contribute toward the genetics of common, complex disorders. The evidence we review clearly indicates that further research into sex-dependent selection and the sex-specific genetic architecture of diseases would be rewarding. This would be aided by studies of laboratory and wild animal populations, and by modelling sex-specific effects in genome-wide association data with joint, gene-by-sex interaction tests. We predict that even sexually monomorphic diseases may harbour cryptic sex-specific genetic architecture. Furthermore, empirical evidence suggests that investigating sex-dependent epistasis may be especially rewarding. Finally, the prevalent nature of sex-specific genetic architecture in disease offers scope for the development of more effective, sex-specific therapies.\n\nFundingThis work was supported by the European Research Council (WPG and EHM; Starting Grant #280632), a Royal Society University Research Fellowship (EHM), the Swedish Research Council (JKA), and the Volkswagen Foundation (JKA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\nCompeting interestsThe authors declare that they have no competing financial interests.

Genetics↗

bioRxiv2013

Genome-wide targets of selection: female response to experimental removal of sexual selection in Drosophila melanogaster

Despite the common assumption that promiscuity should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the mating system in replicate populations of Drosophila melanogaster by removing sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies. We show that monogamous females suffer decreased fecundity, a decrease that was partially recovered by experimentally reversing the selection pressure back to the ancestral promiscuous state. The post-mating gene expression profiles of monogamous females differ significantly from promiscuous females, involving 9% of the genes tested. These transcripts are active in several tissues, mainly ovaries, neural tissues and midgut, and are involved in metabolic processes, reproduction and signaling pathways. Our results demonstrate how the female post-mating response can evolve under different mating systems, and provide novel insights into the genes targeted by sexual selection in females, by identifying a list of candidate genes responsible for the decrease in female fecundity in the absence of promiscuity.

Evolutionary Biology↗