Biology subjects

Agrawal, A. F.

Publications and source records attributed to Agrawal, A. F..

15 recordsLinked to original sources

bioRxiv2026

Sex-biased expression in whole bodies, tissues and cell-types: patterns across and within levels

Whole body transcriptomes have been widely used to study the evolution of sex-biased genes, yet it remains unclear what whole body sex bias represents biologically. Using the FlyAtlas2 and Fly Cell Atlas datasets from Drosophila melanogaster, we show that whole body sex bias emerges from both sex-biased regulation within smaller biological units and how genes are expressed these across units, the latter indicating the contribution of compositional differences to whole body sex bias. Despite these compositional effects, the direction of whole body sex bias is generally consistent with that observed across most tissues and cell-types because sex bias tends to be positively correlated among tissues and among cell-types. Genes which display sex-biased expression across multiple tissues/cell-types typically exhibit the greatest magnitude of sex bias in reproductive tissues/cell-types, consistent with widespread pleiotropic spillover from reproductive components. Among genes lacking gonadal sex bias, the magnitude of sex-biased expression is often greatest in tissues where genes are less highly expressed, further suggesting the role of pleiotropy. In revisiting the evolutionary patterns with respect to tissue level sex bias, we find that elevated rates of adaptive evolution among gonad-expressed sex-biased genes are better explained by their greater expression localization in the reproductive tissues, rather than by their sex bias itself. However, among genes not expressed in the gonads, strong male-biased expression in non-gonadal tissues remains independently associated with increased adaptive evolution. Together, our results show that whole body sex bias is a meaningful summary of broad-scale sex-biased expression though may obscure finer-scale evolutionary signals.

evolutionary biology↗

bioRxiv2026

Local Adaptation to the Sex Environment: Reciprocal Sex-Limited Selection in Different Thermal Regimes

The shared genome prevents each sex from independently responding to the selection experienced by that sex. We used experimental evolution in Drosophila melanogaster with separate pools of Chromosome 3s for males (male-limited chromosomes) and females (female-limited chromosomes) for 15 generations. Viewing each sex as a separate environment, we performed a reciprocal transplant between the sexes to quantify the strength of local adaptation to each sex environment. Each chromosome type was more beneficial in the sex it had been selected for (i.e., local adaptation to sex). Because it has been postulated that sex differences in selection may depend on how well adapted a population is to the abiotic environment, we performed experimental evolution at two thermal regimes: one benign temperature to which the populations were well-adapted and one novel temperature. Female-specific adaptation was stronger at the benign temperature whereas male-specific adaptation was stronger in the novel temperature. Within chromosome pools, male and female fitness were more positively correlated in the novel compared to the benign temperature. Though males carrying male-limited chromosomes were typically more fit than males carrying female-limited chromosomes, they were also more harmful to their female mating partners.

evolutionary biology↗

bioRxiv2025

Response of mate harm to sex-separated gene pools

Competition among males to fertilize females can generate sex differences in selection. At the genetic level, alternative alleles can be favoured in each sex (intralocus sexual conflict, IASC). At the phenotypic level, males can evolve traits that are harmful to the females with whom they interact. Here we used experimental evolution in Drosophila melanogaster to examine how relaxing IASC affected the evolution of mate harm. Genetically variable Chromosome 2s evolved in two separate pools within each population. One pool experienced patrilinear inheritance (segregated like a Y-chromosome) and male-limited selection, while the alternative pool segregated like an X-chromosome and experienced female-biased selection. We measured female fitness when exposed to males carrying either chromosome type at either normal (continuous) or reduced (periodic) male exposure, over three time periods. Males carrying either type of chromosome were harmful to females, but males carrying a male-limited chromosome displayed increased harmfulness, suggesting ongoing selection for mate harm that is constrained under normal inheritance. The magnitude and direction of the effect of male interaction on female fitness was highly sensitive to time of measurement, and we observed a brief period where increased interaction with males was beneficial to females.

evolutionary biology↗

bioRxiv2025

Genomic response to sex-separated gene pools

Males and females experience differences in the strength and direction of selection but discerning the type of genes that are targets of sex differences in selection is complicated by their shared genome. We used experimental evolution in Drosophila melanogaster to partially separate the gene pools of males and females for 130 generations. In six replicate populations, we forced one pool of genetically variable Chromosome 2s to experience patrilinear inheritance (segregating like a Y-chromosome) and male-limited selection. The alternative pool segregated like an X-chromosome and experienced female-biased selection. This allowed alleles which are differentially selected for between the sexes to diverge between these pools, enabling us to gain insight into the type of genes subject to such selection. We find that genes which diverge between these pools have an elevated intersexual genetic correlation(rMF) for expression on average, consistent with the idea that high genetic correlations may hinder sex-specific adaptation under normal inheritance. Diverged genes were also enriched for moderately male-biased genes whereas female-biased genes were underrepresented. At the SNP level, we find an overrepresentation of diverged SNPs involved in splicing or occurring in the 5UTR and an underrepresentation of missense or synonymous SNPs, suggesting sex differences in selection for isoform usage.

evolutionary biology↗

bioRxiv2024

Expression divergence in response to sex-biased selection

It remains debated whether greater degrees of sexual dimorphism would evolve if not for intersexual genetic constraints. Here we used experimental evolution to partially break the intersexual genetic constraint in Drosophila melanogaster to investigate the effects of a shared gene pool on the evolution of sexual dimorphism in gene expression. In six replicate populations of 1000 flies, a dominant marker (DsRed) was used to force a "Red" pool of genetically variable Chromosome 2 copies through exclusive father-to-son inheritance, while a complimentary pool of "NonRed" chromosomes was inherited primarily from mothers to daughters. After 100 generations, we demonstrated the effect of Red male-limited chromosomes in increasing male mating success. Differentially expressed genes between flies with and without Red chromosomes had on average higher intersexual genetic correlations (rMF), as expected if such correlations represent a constraint to sex-specific adaptation under normal inheritance. If conflict hinders the evolution of further dimorphism, the transcriptomes of male-selected Red chromosomes were predicted to evolve to be "masculinized" relative to female-selected NonRed chromosomes. Consistent with this, splicing patterns in Red males (but not Red females) were masculinized relative to NonRed males. Contrastingly, gene expression levels were largely feminized in Red flies of both sexes compared to NonRed. We discuss alternative forms of intralocus sexual conflict that may explain these patterns.

evolutionary biology↗

bioRxiv2023

The evolution of sexual dimorphism in gene expression in response to a manipulation of mate competition

Many genes are differentially expressed between males and females and patterns of sex-biased gene expression (SBGE) vary among species. Some of this variation is thought to have evolved in response to differences in mate competition among species that causes varying patterns of sex-specific selection. We used experimental evolution to test this by quantifying SBGE and sex-specific splicing in 15 Drosophila melanogaster populations that evolved for 104 generations in mating treatments that removed mate competition via enforced monogamy, or allowed mate competition in either small, simple or larger, structurally more complex mating environments. Consistent with sex-specific selection affecting SBGE, initially sex-biased genes diverged in expression more among treatments than unbiased genes, and there was greater expression divergence for male-than female-biased genes. It has been suggested the transcriptome should be feminized under monogamy because of the removal of sexual selection on males; we did not observe this, likely because selection differs in additional ways between monogamy vs. polygamy. Significant divergence in average expression dimorphism between treatments was observed and, in some treatment comparisons, the direction of the divergence differed across different sex-bias categories. There was not a generalized reduction in expression dimorphism under enforced monogamy.

evolutionary biology↗

bioRxiv2022

Cis-regulatory variation in relation to sex and sexual dimorphism in Drosophila melanogaster

Much of sexual dimorphism is likely due to sex-biased gene expression, which results from differential regulation of a genome that is largely shared between males and females. Here we use allele-specific expression to explore cis-regulatory variation in Drosophila melanogaster in relation to sex. We develop a Bayesian framework to infer the transcriptome-wide joint distribution of cis-regulatory effects across the sexes. We use this approach to quantify transcriptome-wide sex differences in cis-regulatory effects as well as examine patterns of cis-regulatory variation with respect to two other levels of variation in sexual dimorphism: (i) across genes varying in their degree of sex-biased expression, and (ii) among tissues that vary in their degree of dimorphism (e.g., relatively low dimorphism in heads vs high dimorphism in gonads). We uncover evidence of widespread cis-regulatory variation in all tissues examined, with female-biased genes being especially enriched for this variation. A sizeable proportion of cis-regulatory variation is inferred to have sex-specific effects, with sex-dependent cis effects being much more frequent in gonads than in heads. Finally, we detect some genes with reversed allelic imbalance between the sexes. Such variants could provide a mechanism for sex-specific dominance reversals, a phenomenon important for sexually antagonistic balancing selection.

evolutionary biology↗

bioRxiv2022

An investigation of the sex-specific genetic architecture of fitness in Drosophila melanogaster

In dioecious populations, the sexes employ divergent reproductive strategies to maximize fitness and, as a result, genetic variants can affect fitness differently in males and females. Moreover, recent studies have highlighted an important role of the mating environment in shaping the strength and direction of sex-specific selection. Here, we measure adult fitness for each sex of 357 lines from the Drosophila Synthetic Population Resource (DSPR) in two different mating environments. We analyze the data using three different approaches to gain insight into the sex-specific genetic architecture for fitness: classical quantitative genetics, genomic associations, and a mutational burden approach. The quantitative genetics analysis finds that, on average segregating genetic variation in this population has concordant fitness effects both across the sexes and across mating environments. We do not find specific genomic regions with strong associations with either sexually antagonistic (SA) or sexually concordant (SC) fitness effects, yet there is modest evidence of an excess of genomic regions with weak associations, both with SA and SC fitness effects. Our examination of mutational burden indicates stronger selection against indels and loss-of-function variants in females than males.

evolutionary biology↗

bioRxiv2021

Sexual dimorphism in gene expression: coincidence and population genomics of two forms of differential expression in Drosophila melanogaster

Phenotypic sexual dimorphism can be mediated by sex differences in gene expression. We examine two forms of sexual dimorphism in gene expression in Drosophila melanogaster: (i) sex-biased gene expression (SBGE) in which the sexes differ in the amount a gene is expressed and (ii) sexual dimorphism in isoform usage, i.e., sex-specific splicing (SSS). In whole body (but not head) expression, we find a negative association between SBGE and SSS, possibly suggesting these are alternate routes to resolving sexual antagonistic selection. Next, we evaluate whether expression dimorphism contributes to the heterogeneity among genes in rmf, the intersexual genetic correlation in body expression that constrains the extent to which a genes expression can evolve independently between the sexes. We find lower rmf values for genes with than without SSS. We find higher rmf values for male- than female-biased genes (except genes with extreme male-bias), even though male-biased genes are known to have greater evolutionary divergence in expression. Finally, we examine population genetic patterns in relation to SBGE and SSS because genes with expression dimorphism have likely experienced a history of sex differences in selection. SSS is associated with reduced values of Tajimas D and elevated Direction of Selection (DoS) values, suggestive of higher rates of adaptive evolution. Though DoS is highly elevated for genes with extreme male bias, DoS otherwise tends to decline from female-biased to unbiased to male-biased genes. Collectively, the results indicate that SBGE and SSS are differentially distributed across the genome and are associated with different forms of selection.

evolutionary biology↗

bioRxiv2020

Using Patterns of Signed Linkage Disequilibria to Test for Epistasis in Flies and Plants

Most empirical studies of linkage disequilibrium (LD) study its magnitude, ignoring its sign. Here, we examine patterns of signed LD in two population genomic datasets, one from Capsella grandiflora and one from Drosophila melanogaster. We consider how processes such as drift, admixture, Hill-Robertson interference, and epistasis may contribute to these patterns. We report that most types of mutations exhibit positive LD, particularly, if they are predicted to be less deleterious. We show with simulations that this pattern arises easily in a model of admixture or distance biased mating, and that genome-wide differences across site types are generally expected due to differences in the strength of purifying selection even in the absence of epistasis. We further explore how signed LD decays on a finer scale, showing that loss of function mutations exhibit particularly positive LD across short distances, a pattern consistent with intragenic antagonistic epistasis. Controlling for genomic distance, signed LD in C. grandiflora decays faster within genes, compared to between genes, likely a by-product of frequent recombination in gene promoters known to occur in plant genomes. Finally, we use information from published biological networks to explore whether there is evidence for negative synergistic epistasis between interacting radical missense mutations. In D. melanogaster networks, we find a modest but significant enrichment of negative LD, consistent with the possibility of intra-network negative synergistic epistasis.

genomics↗

bioRxiv2020

Estimation of the SNP mutation rate in two vegetatively propagating species of duckweed

Mutation rate estimates for vegetatively reproducing organisms are rare, despite their frequent occurrence across the tree of life. Here we report mutation rate estimates in two vegetatively reproducing duckweed species, Lemna minor and Spirodela polyrhiza. We use a modified approach to estimating mutation rates by taking into account the reduction in mutation detection power that occurs when new individuals are produced from multiple cell lineages. We estimate an extremely low per generation mutation rate in both species of duckweed and note that allelic coverage at de novo mutation sites is very skewed. We also find no substantial difference in mutation rate between mutation accumulation lines propagated under benign conditions and those grown under salt stress. Finally, we discuss the implications of interpreting mutation rate estimates in vegetatively propagating organisms.

genomics↗

bioRxiv2017

Mutation accumulation in selfing populations under fluctuating selection

Selfing species are prone to extinction, possibly because highly selfing populations can suffer from a continuous accumulation of deleterious mutations, a process analogous to Mullers ratchet in asexual populations. However, current theory provides little insight into which types of genes are most likely to accumulate deleterious alleles and what environmental circumstances may accelerate genomic degradation. Here we investigate temporal changes in the environment that cause fluctuations in the strength of purifying selection. We simulate selfing populations with genomes containing a mixture of loci experiencing constant selection and loci experiencing selection that fluctuates in strength (but not direction). Even when both types of loci experience the same average strength of selection, loci under fluctuating selection contribute disproportionately more to deleterious mutation accumulation. Moreover, the presence of loci experiencing fluctuating selection in the genome increases the deleterious fixation rate at loci under constant selection; under most realistic scenarios this effect of linked selection can be attributed to a reduction in Ne. Fluctuating selection is particularly injurious when selective environments are strongly autocorrelated over time and when selection is concentrated into rare bouts of strong selection. These results imply that loci under fluctuating selection are likely important drivers of extinction in selfing species.

evolutionary biology↗

bioRxiv2017

Virulence evolution of a parasite infecting male and female hosts

Parasites experience different tradeoffs between transmission and virulence in male and female hosts if the sexes vary in life history or disease-related traits. We determine the evolutionarily stable levels of exploitation by pathogens under two scenarios: an unconstrained pathogen that expresses different exploitation rates within each host type as well as a pathogen constrained to express the same exploitation rate in each sex. We show that an unconstrained horizontally-transmitted parasite evolves to express the same sex-specific exploitation rate within each sex as it would in a host population composed entirely of hosts with that sexs resistance and intrinsic death rate. In contrast, the ESS exploitation rate of a constrained pathogen is affected by sex-differences in susceptibility and non-random contact patterns between host types that differ in resistance. As the amount of within-sex transmission increases, the ESS shifts closer to the optimum trait value in the more susceptible sex. Allowing for some degree of vertical transmission, the exploitation rate expressed in females (but not males) changes with contact pattern even in unconstrained pathogens. Differences in contact pattern and susceptibility play an important role in determining the ESS exploitation rate by shifting the reproductive value of each host type.

evolutionary biology↗

bioRxiv2017

Sexual conflict and STDs: coevolution of sexually antagonistic host traits with a sexually transmitted disease

In many taxa, there is a conflict between the sexes over mating rate. The outcome of sexually antagonistic coevolution depends on the costs of mating and natural selection against sexually antagonistic traits. A sexually transmitted infection (STI) changes the relative strength of these costs. We study the three-way evolutionary interaction between male persistence, female resistance, and STI virulence for two types of STIs: a viability-reducing STI and a reproduction-reducing STI. A viability-reducing STI escalates conflict between the sexes. This leads to increased STI virulence (i.e., full coevolution) if the costs of sexually antagonistic traits occur through viability but not if the costs occur through reproduction. In contrast, a reproduction-reducing STI de-escalates the sexual conflict but STI virulence does not coevolve in response. We also investigated the establishment probability of STIs under different combinations of evolvability. Successful invasion by a viability-reducing STI becomes less likely if hosts (but not parasite) are evolvable, especially if only the female trait can evolve. A reproduction-reducing STI can almost always invade because it does not kill its host. We discuss how the evolution of host and parasite traits in a system with sexual conflict differ from a system with female mate choice.

evolutionary biology↗

bioRxiv2017

An experimental test of the mutation-selection balance model for the maintenance of genetic variance in fitness components

Despite decades of research, the factors that maintain genetic variation for fitness are poorly understood. Mutation selection balance will always contribute to standing variance, but it is unclear what fraction of the variance in a typical fitness component can be explained by mutation-selection balance and whether fitness components differ in this respect. In theory, the level of standing variance in fitness due to mutation-selection balance can be predicted using the rate of fitness decline under mutation accumulation, and this prediction can be directly compared to the actual standing variance observed. This approach allows for controlled statistical tests of the sufficiency of the mutation-selection balance model, and could be used to identify traits or populations where genetic variance is maintained by factors beyond mutation-selection balance. For example, some traits may be influenced by sexually antagonistic balancing selection, resulting in an excess of standing variance beyond that generated by deleterious mutations. To encourage the application of this approach, we describe the underlying theory and use it to test the mutation selection balance model for three traits in Drosophila melanogaster. We find some evidence for non-mutational variance in male mating success and female fecundity relative to larval viability, which is consistent with balancing selection on sexual fitness components. Finally, we discuss the theoretical and practical limitations to this approach, and discuss how to apply it successfully.

evolutionary biology↗