One of Ernst Mayr's legacies is the consensus that the allopatry model is the predominant mode of speciation in most sexually reproducing lineages. In this model, reproductive isolation develops as a pleiotropic byproduct of the genetic divergence that develops among physically isolated populations. Presently, there is no consensus concerning which, if any, evolutionary process is primarily responsible for driving the specific genetic divergence that leads to reproductive isolation. Here, we focus on the hypothesis that inter-locus antagonistic coevolution drives rapid genetic divergence among allopatric populations and thereby acts as an important ''engine'' of speciation. We assert that only data from studies of experimental evolution, rather than descriptive patterns of molecular evolution, can provide definitive evidence for this hypothesis. We describe and use an experimental approach, called hemiclonal analysis, that can be used in the Drosophila melanogaster laboratory model system to simultaneously screen nearly the entire genome for both standing genetic variation within a population and the net-selection gradient acting on the variation. Hemiclonal analysis has four stages: (i) creation of a laboratory ''island population''; (ii) cytogenetic cloning of nearly genomewide haplotypes to construct hemiclones; (iii) measurement of additive genetic variation among hemiclones; and (iv) measurement of the selection gradient acting on phenotypic variation among hemiclones. We apply hemiclonal analysis to test the hypothesis that there is ongoing antagonistic coevolution between the sexes in the D. melanogaster laboratory model system and then discuss the relevance of this analysis to natural systems.sexual conflict ͉ inter-locus contest evolution ͉ sexually antagonistic coevolution ͉ reproductive isolation ͉ genetic divergence

We describe a graphical model of interlocus coevolution used to distinguish between the interlocus sexual conflict that leads to sexually antagonistic coevolution, and the intrinsic conflict over mating rate that is an integral part of traditional models of sexual selection. We next distinguish the 'laboratory island' approach from the study of both inbred lines and laboratory populations that are newly derived from nature, discuss why we consider it to be one of the most fitting forms of laboratory analysis to study interlocus sexual conflict, and then describe four experiments using this approach with Drosophila melanogaster. The first experiment evaluates the efficacy of the laboratory model system to study interlocus sexual conflict by comparing remating rates of females when they are, or are not, provided with a spatial refuge from persistent male courtship. The second experiment tests for a lag-load in males that is due to adaptations that have accumulated in females, which diminish male-induced harm while simultaneously interfering with a male's ability to compete in the context of sexual selection. The third and fourth experiments test for a lag-load in females owing to direct costs from their interactions with males, and for the capacity for indirect benefits to compensate for these direct costs.

Reproductive costs are an essential component of evolutionary theory. For instance, an increase in reproduction is generally coupled with a decrease in immunocompetence shortly after mating. However, recent work in Drosophila melanogaster suggests that the potential to mount an immune response, as measured by the levels of immune gene expression, increases after mating. These data are in contrast to previous studies, which suggest that mating can reduce a fly's ability to survive an actual bacterial challenge (realized immunity). This pattern may be driven by some aspect of mating, independent of resource limitation, which reduces immune function by inhibiting the effective deployment of immune gene products. Though several studies have examined both the potential and the realized immunity after mating, none have examined these immune measures simultaneously. Here, we examined the link between the potential and the realized immunity in a sterile mutant of D. melanogaster. Shortly after mating, we found that female immune gene expression was high, but survival against infection was low. Surprisingly, this pattern was reversed within 24 h. Thus, estimates of immunity based on gene expression do not appear to reflect an actual ability to defend against pathogens in the hours following copulation. We discuss the possible mechanisms that may account for this pattern.

The sexual conflict hypothesis predicts that males evolve traits that exploit the higher parental investment of females, which generates selection for females to counter‐evolve resistance. In Drosophila melanogaster it is now established that males harm females and that there is genetic variation among males for the degree of this harm. Genetic variation among females for resistance to harm from males, and the corresponding strength of selection on this variation, however, have not been quantified previously. Here we carryout a genome‐wide screen for female resistance to harm from males. We estimate that the cost of interactions with males depresses lifetime fecundity of females by 15% (95% CI: 8.2–22.0), that genetic variation for female resistance constitutes 17% of total genetic variation for female adult fitness, and that propensity to remate in response to persistent male courtship is a major factor contributing to genetic variation for female resistance.

The empirical foundation for sexual conflict theory is the data from many different taxa demonstrating that females are harmed while interacting with males. However, the interpretation of this keystone evidence has been challenged because females may more than counterbalance the direct costs of interacting with males by the indirect benefits of obtaining higher quality genes for their offspring. A quantification of this trade‐off is critical to resolve the controversy and is presented here. A multi‐generation fitness assay in the Drosophila melanogaster laboratory model system was used to quantify both the direct costs to females due to interactions with males and indirect benefits via sexy sons. We specifically focus on the interactions that occur between males and nonvirgin females. In the laboratory environment of our base population, females mate soon after eclosion and store sufficient sperm for their entire lifetime, yet males persistently court these nonvirgin females and frequently succeed in re‐mating them. Females may benefit from these interactions despite direct costs to their lifetime fecundity if re‐mating allows them to trade‐up to mates of higher genetic quality and thereby secure indirect benefits for their offspring. We found that direct costs of interactions between males and nonvirgin females substantially exceeded indirect benefits through sexy sons. These data, in combination with past studies of the good genes route of indirect benefits, demonstrate that inter‐sexual interactions drive sexually antagonistic co‐evolution in this model system.

Background Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. Objective To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. Methods A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. Results HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P <.001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). Conclusions HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.

Drosophila melanogaster is widely used to study immune system function in insects. However, little work has been done in D. melanogaster on the effect of temperature on the immune system.Here we describe experiments that demonstrate that cooler temperatures enhance survival after infection and alter expression of immune-related genes in flies. This effect appears to be due not only to the fact that colder temperatures slow down bacterial growth, but also to the beneficial effects of cooler temperature on immune function. We explore the possibility that heat shock proteins, and in particular, Hsp83, may improve immune function at cool temperatures. We have long known that temperature can alter immune responses against microbial pathogens in insects. The approach described here allows us to determine whether this effect is due primarily to temperature-specific effects on the host or on its pathogen. These results suggest that both may be important.

The eMERGE Consortium* , * The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.