Multivariate genetic architecture reveals testosterone-driven sexual antagonism in contemporary humans.

Sex difference (SD) is ubiquitous in humans despite shared genetic architecture (SGA) between the sexes. A univariate approach, i.e., studying SD in single traits by estimating genetic correlation, does not provide a complete biological overview, because traits are not independent and are genetically correlated. The multivariate genetic architecture between the sexes can be summarized by estimating the additive genetic (co)variance across shared traits, which, apart from the cross-trait and cross-sex covariances, also includes the cross-sex-cross-trait covariances, e.g., between height in males and weight in females. Using such a multivariate approach, we investigated SD in the genetic architecture of 12 anthropometric, fat depositional, and sex-hormonal phenotypes. We uncovered sexual antagonism (SA) in the cross-sex-cross-trait covariances in humans, most prominently between testosterone and the anthropometric traits - a trend similar to phenotypic correlations. 27% of such cross-sex-cross-trait covariances were of opposite sign, contributing to asymmetry in the SGA. Intriguingly, using multivariate evolutionary simulations, we observed that the SGA acts as a genetic constraint to the evolution of SD in humans only when selection is sexually antagonistic and not concordant. Remarkably, we found that the lifetime reproductive success in both the sexes shows a positive genetic correlation with anthropometric traits, but not with testosterone. Moreover, we demonstrated that genetic variance is depleted along multivariate trait combinations in both the sexes but in different directions, suggesting absolute genetic constraint to evolution. Our results indicate that testosterone drives SA in contemporary humans and emphasize the necessity and significance of using a multivariate framework in studying SD.

Comparative analysis of the multivariate genetic architecture of morphological traits in three species of Gomphocerine grasshoppers.

Evolutionary change is the change in trait values across generations, and usually occurs in multidimensional trait space rather than along isolated traits. Genetic covariation influences the magnitude and direction of evolutionary change and can be statistically summarized by the additive genetic (co)variance matrix, G. While G can affect the response to selection, it is exposed to evolutionary change by selection and genetic drift, but the magnitude and speed of these changes are poorly understood. We use comparative G matrix analyses to assess evolution of the shape and orientation of G over longer timescales in three species of Gomphocerine grasshoppers. We estimate 10 × 10 G matrices for five morphological traits expressed in both sexes. We find low-to-moderate heritabilities (average 0.36), mostly large cross-sex correlations (average 0.54) and moderate between-trait correlations (average 0.34). G matrices differ significantly among species with wing length contributing most to these differences. Wing length is the trait that is most divergent among species, suggesting it has been under selection during species divergence. The more distantly related species, Pseudochorthippus parallelus, was the most different in the shape of G. Projection of contemporary genetic variation into the divergence space D illustrates that the major axis of genetic variation in Gomphocerippus rufus is aligned with divergence from Chorthippus biguttulus, while the major axis of genetic variation in neither of the species is aligned with the divergence between Pseudochorthippus parallelus and the other two species. Our results demonstrate significant differences in G matrices with a phylogenetic signal in the differentiation.

Direct and indirect genetic effects on reproductive investment in a grasshopper.

A fundamental part of the quantitative genetic theory deals with the partitioning of the phenotypic variance into additive genetic and environmental components. During interaction with conspecifics, the interaction partner becomes a part of the environment from the perspective of the focal individual. If the interaction effects have a genetic basis, they are called indirect genetic effects (IGEs) and can evolve along with direct genetic effects. Sexual reproduction is a classic context where potential conflict between males and females can arise from trade-offs between current and future investments. We studied five female fecundity traits, egg length and number, egg pod length and number and latency to first egg pod, and estimated the direct and IGEs using a half-sib breeding design in the grasshopper Chorthippus biguttulus. We found that the male IGEs were an order of magnitude lower than the direct genetic effects and were not significantly different from zero. However, there was some indication that IGEs were larger shortly after mating, consistent with the idea that IGEs fade with time after interaction. Female direct heritabilities were moderate to low. Simulation shows that the variance component estimates can appear larger with less data, calling for care when interpreting variance components estimated with low power. Our results illustrate that the contribution of male IGEs is overall low on the phenotypic variance of female fecundity traits. Thus, even in the relevant context of sexual conflict, the influence of male IGEs on the evolutionary trajectory of female reproductive traits is likely to be small.