Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies.

The evolution of sexual dimorphism is constrained by a shared genome, leading to 'sexual antagonism', in which different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we propose that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation

Female responses to experimental removal of sexual selection components in Drosophila melanogaster

Despite the common assumption that multiple mating 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 opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies

Genetic approaches to the development of novel designs for population control of two vector mosquitoes: Aedes aegypti and Culex quinquefasciatus.: Genetically engineered late-acting lethality as a strategy for control of invasive vector mosquitoes.

The prevention or reduction of infectious pathogen transmission is essential for safeguarding human health and species conservation, and can be achieved through vector control. New genetics-based innovations have proven to be a viable solution for the successful suppression or eradication of insect vectors, whilst also providing opportunities for further improvements and enhancements. In this thesis, I examine a vector control approach incorporating genetically engineered late-acting lethality, and investigate the character and function of the genetic elements that could lead to improvement of this approach. I start by assessing the functionality of the late-acting, doxycycline-repressible lethal system in transgenic Aedes aegypti. I find that the induced lethality is specific to the late developmental stage and occurs in the vast majority of the individuals carrying the lethal transgene. I also show that the induced phenotype is strongly repressible in the presence of the antidote, which is a crucial prerequisite of a practical RIDL (Release of Insect carrying Dominant Lethal gene) system. Next, I investigate the Culex quinquefasciatus Actin-4 gene and its potential use to induce a flightless phenotype. I find that the expression of the Actin-4 is sex-specific and, by generating a novel mutant via gene editing, that the gene is haploinsufficient or dominant negative in inducing the flightless phenotype in females. Additionally, I provide further support for the effectiveness of the recently discovered CRISPR/Cas9 system by showing that it successfully induces targeted editing of the Actin-4 gene. My findings provide novel genetic tools for the development of various genetics-based strategies for control of invasive vector mosquitoes

Genetic approaches to the development of novel designs for population control of two vector mosquitoes: Aedes aegypti and Culex quinquefasciatus.

The prevention or reduction of infectious pathogen transmission is essential for safeguarding human health and species conservation, and can be achieved through vector control. New genetics-based innovations have proven to be a viable solution for the successful suppression or eradication of insect vectors, whilst also providing opportunities for further improvements and enhancements. In this thesis, I examine a vector control approach incorporating genetically engineered late-acting lethality, and investigate the character and function of the genetic elements that could lead to improvement of this approach. I start by assessing the functionality of the late-acting, doxycycline-repressible lethal system in transgenic Aedes aegypti. I find that the induced lethality is specific to the late developmental stage and occurs in the vast majority of the individuals carrying the lethal transgene. I also show that the induced phenotype is strongly repressible in the presence of the antidote, which is a crucial prerequisite of a practical RIDL (Release of Insect carrying Dominant Lethal gene) system. Next, I investigate the Culex quinquefasciatus Actin-4 gene and its potential use to induce a flightless phenotype. I find that the expression of the Actin-4 is sex-specific and, by generating a novel mutant via gene editing, that the gene is haploinsufficient or dominant negative in inducing the flightless phenotype in females. Additionally, I provide further support for the effectiveness of the recently discovered CRISPR/Cas9 system by showing that it successfully induces targeted editing of the Actin-4 gene. My findings provide novel genetic tools for the development of various genetics-based strategies for control of invasive vector mosquitoes

Genetic approaches to the development of novel designs for population control of two vector mosquitoes: Aedes aegypti and Culex quinquefasciatus.

The prevention or reduction of infectious pathogen transmission is essential for safeguarding human health and species conservation, and can be achieved through vector control. New genetics-based innovations have proven to be a viable solution for the successful suppression or eradication of insect vectors, whilst also providing opportunities for further improvements and enhancements. In this thesis, I examine a vector control approach incorporating genetically engineered late-acting lethality, and investigate the character and function of the genetic elements that could lead to improvement of this approach. I start by assessing the functionality of the late-acting, doxycycline-repressible lethal system in transgenic Aedes aegypti. I find that the induced lethality is specific to the late developmental stage and occurs in the vast majority of the individuals carrying the lethal transgene. I also show that the induced phenotype is strongly repressible in the presence of the antidote, which is a crucial prerequisite of a practical RIDL (Release of Insect carrying Dominant Lethal gene) system. Next, I investigate the Culex quinquefasciatus Actin-4 gene and its potential use to induce a flightless phenotype. I find that the expression of the Actin-4 is sex-specific and, by generating a novel mutant via gene editing, that the gene is haploinsufficient or dominant negative in inducing the flightless phenotype in females. Additionally, I provide further support for the effectiveness of the recently discovered CRISPR/Cas9 system by showing that it successfully induces targeted editing of the Actin-4 gene. My findings provide novel genetic tools for the development of various genetics-based strategies for control of invasive vector mosquitoes

Data from: Female responses to experimental removal of sexual selection in Drosophila melanogaster

Background: Despite the common assumption that multiple mating 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 opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies. Results: We show that monogamous females suffer decreased fecundity, a decrease that was partially recovered by experimentally reversing the selection pressure back to the ancestral state. The post-mating gene expression profiles of monogamous females differ significantly from promiscuous females, involving 9% of the genes tested (approximately 6% of total genes in D. melanogaster). These transcripts are active in several tissues, mainly ovaries, neural tissues and midgut, and are involved in metabolic processes, reproduction and signaling pathways. Conclusions: 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

Data from: Heritability of lifespan is largely sex-limited in Drosophila

Males and females differ with respect to lifespan and rate of aging in most animal species. Such sexual dimorphism can be associated with a complex genetic architecture, where only part of the genetic variation is shared between the sexes. To the extent this is true for lifespan and aging is not known, since studies of lifespan have given contradictory results and because aging has not been studied from this perspective. Here we investigate the additive genetic architecture of lifespan and aging in Drosophila melanogaster. We find substantial amounts of additive genetic variation for both traits, and that more than three quarters of this variation is available for sex-specific evolutionary change. This result shows that the sexes have a profoundly different additive genetic basis for these traits, which has several implications. First it translated into an, on average, three times higher heritability of lifespan within compared to between the sexes. Second, it implies that the sexes are relatively free to evolve with respect to these traits. And third, as lifespan and aging are traits that integrate over all genetic factors that contribute to mortal disease, it also implies that the genetics of heritable disease differs vastly between the sexes

Heritability of life span is largely sex limited in Drosophila

Lehtovaara A, Schielzeth H, Flis I, Friberg U. Heritability of life span is largely sex limited in Drosophila. The American Naturalist. 2013;182(5):653-665.Males and females differ with respect to life span and rate of aging in most animal species. Such sexual dimorphism can be associated with a complex genetic architecture, where only part of the genetic variation is shared between the sexes. However, the extent to which this is true for life span and aging is not known, because studies of life span have given contradictory results and aging has not been studied from this perspective. Here we investigate the additive genetic architecture of life span and aging in Drosophila melanogaster. We find substantial amounts of additive genetic variation for both traits, with more than three-quarters of this variation available for sex-specific evolutionary change. This result shows that the sexes have a profoundly different additive genetic basis for these traits, which has several implications. First, it translates into an, on average, three-times-higher heritability of life span within, compared to between, the sexes. Second, it implies that the sexes are relatively free to evolve with respect to these traits. And third, as life span and aging are traits that integrate over all genetic factors that contribute to mortal disease, it also implies that the genetics of heritable disease differs vastly between the sexes