Population,evolutionary and genomic consequences of interference selection

Weakly selected mutations are most likely to be physically clustered across genomes and, when sufficiently linked, they alter each others' fixation probability, a process we call interference selection (IS). Here we study population genetics and evolutionary consequences of IS on the selected mutations themselves and on adjacent selectively neutral variation. We show that IS reduces levels of polymorphism and increases low-frequency variants and linkage disequilibrium, in both selected and adjacent neutral mutations. IS can account for several well-documented patterns of variation and composition in genomic regions with low rates of crossing over in Drosophila. IS cannot be described simply as a reduction in the efficacy of selection and effective population size in standard models of selection and drift. Rather, IS can be better understood with models that incorporate a constant "traffic" of competing alleles. Our simulations also allow us to make genome-wide predictions that are specific to IS. We show that IS will be more severe at sites in the center of a region containing weakly selected mutations than at sites located close to the edge of the region. Drosophila melanogaster genomic data strongly support this prediction, with genes without introns showing significantly reduced codon bias in the center of coding regions. As expected, if introns relieve IS, genes with centrally located introns do not show reduced codon bias in the center of the coding region. We also show that reasonably small differences in the length of intermediate "neutral" sequences embedded in a region under selection increase the effectiveness of selection on the adjacent selected sequences. Hence, the presence and length of sequences such as introns or intergenic regions can be a trait subject to selection in recombining genomes. In support of this prediction, intron presence is positively correlated with a gene's codon bias in D. melanogaster. Finally, the study of temporal dynamics of IS after a change of recombination rate shows that nonequilibrium codon usage may be the norm rather than the exception.     

Sex differences in mate selection strategies: Content analyses and responses to personal advertisements in Brazil

We studied mate selection strategies as revealed in heterosexual personal advertisements published in a Brazilian newspaper, analyzing both the ads' content, with respect to the attributes that men and women offered and sought, and predictors of the number of responses that each ad received. Demands made for a prospective partner changed as a function of the age of the advertiser in predictable sex-differentiated ways: women became less demanding as they aged, whereas men became more demanding. The number of responses received by men and women as a function of age followed a similarly sex-differentiated pattern, with older women receiving fewer responses than younger women, and older men receiving more responses than younger men. In general, results of the present study provided support for our predictions. People who used personal advertisements, a relatively recent unconventional way for selecting mates, expressed conventional preferences, suggestive of evolved psychological mechanisms.     

Sex differences in immune responses to SARS-CoV-2 in patients with COVID-19

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3⁺ and CD8⁺ T cell proportions. The lower CD4⁺ T cell proportions and higher CD8⁺ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4⁺ T cell proportion was negatively associated with the CD8⁺ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4⁺ T cell and CD8⁺ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.     

Sexual selection and its evolutionary consequences in female animals

For sexual selection to act on a given sex, there must exist variation in the reproductive success of that sex as a result of differential access to mates or fertilisations. The mechanisms and consequences of sexual selection acting on male animals are well documented, but research on sexual selection acting on females has only recently received attention. Controversy still exists over whether sexual selection acts on females in the traditional sense, and over whether to modify the existing definition of sexual selection (to include resource competition) or to invoke alternative mechanisms (usually social selection) to explain selection acting on females in connection with reproduction. However, substantial evidence exists of females bearing characters or exhibiting behaviours that result in differential reproductive success that are analogous to those attributed to sexual selection in males. Here we summarise the literature and provide substantial evidence of female intrasexual competition for access to mates, female intersexual signalling to potential mates, and postcopulatory mechanisms such as competition between eggs for access to sperm and cryptic male allocation. Our review makes clear that sexual selection acts on females and males in similar ways but sometimes to differing extents: the ceiling for the elaboration of costly traits may be lower in females than in males. We predict that current and future research on female sexual selection will provide increasing support for the parsimony and utility of the existing definition of sexual selection.     

Sex: differences in mutation, recombination, selection, gene flow, and genetic drift

In many instances, there are large sex differences in mutation rates, recombination rates, selection, rates of gene flow, and genetic drift. Mutation rates are often higher in males, a difference that has been estimated both directly and indirectly. The higher male mutation rate appears related to the larger number of cell divisions in male lineages but mutation rates also appear gene- and organism-specific. When there is recombination in only one sex, it is always the homogametic sex. When there is recombination in both sexes, females often have higher recombination but there are many exceptions. There are a number of hypotheses to explain the sex differences in recombination. Sex-specific differences in selection may result in stable polymorphisms or for sex chromosomes, faster evolutionary change. In addition, sex-dependent selection may result in antagonistic pleiotropy or sexually antagonistic genes. There are many examples of sex-specific differences in gene flow (dispersal) and a number of adaptive explanations for these differences. The overall effective population size (genetic drift) is dominated by the lower sex-specific effective population size. The mean of the mutation, recombination, and gene flow rates over the two sexes can be used in a population genetics context unless there are sex-specific differences in selection or genetic drift. Sex-specific differences in these evolutionary factors appear to be unrelated to each other. The evolutionary explanations for sex-specific differences for each factor are multifaceted and, in addition, explanations may include chance, nonadaptive differences, or mechanistic, nonevolutionary factors.     

Sex differences in parental care: Gametic investment,sexual selection,and social environment

Male and female parents often provide different type and amount of care to their offspring. Three major drivers have been proposed to explain parental sex roles: (1) differential gametic investment by males and females that precipitates into sex difference in care, (2) different intensity of sexual selection acting on males and females, and (3) biased social environment that facilitates the more common sex to provide more care. Here, we provide the most comprehensive assessment of these hypotheses using detailed parental care data from 792 bird species covering 126 families. We found no evidence for the gametic investment hypothesis: neither gamete sizes nor gamete production by males relative to females was related to sex difference in parental care. However, sexual selection correlated with parental sex roles, because the male share in care relative to female decreased with both extra‐pair paternity and frequency of male polygamy. Parental sex roles were also related to social environment, because male parental care increased with male‐biased adult sex ratios (ASRs). Taken together, our results are consistent with recent theories suggesting that gametic investment is not tied to parental sex roles, and highlight the importance of both sexual selection and ASR in influencing parental sex roles.     

Sex differences in selection of pacemakers: retrospective observational study

Objective: To evaluate the effect of patients’ sex on selection of pacemakers. Design: Retrospective univariate and multivariate analysis of a large database. Setting: German central pacemaker register. Subjects: Records collected at the register for 1992 and 1993 (n=31 913), covering 64% of all implantations in Germany. Main outcome measure: Probability of receiving a single chamber, dual chamber, or rate responsive pacemaker in relation to sex. Results: Univariate analysis showed that women were more likely to receive single chamber pacemakers and less likely to receive dual chamber or rate responsive systems than men. After demographic and clinical variables were controlled for, women were still more likely to receive a single chamber system (atrial pacing: odds ratio 0.89, 95% confidence interval 0.74 to 1.07; ventricular pacing: 0.85, 0.80 to 0.92) and less likely to receive a dual chamber (1.20, 1.12 to 1.30) or a rate responsive system (1.26, 1.17 to 1.37) than men. Conclusions: The data suggest sex differences in the selection of a pacemaker system which cannot be explained by the underlying cardiac disorder. Further research is needed to evaluate why guidelines for implanting pacemakers are not better adhered to.

Key messages

• Use of pacemakers varies despite guidelines, and the reasons for this are unclear
• In this study women were more likely to receive single chamber pacemakers and less likely to receive dual chamber and rate responsive pacemakers than men
• Demographic and clinical variables cannot fully explain these differences
• Prospective studies are needed to evaluate the effect of sex and other non-medical variables on the selection of pacemakers

     

Sex differences in survival selection in the serin,Serinus serinus

Natural selection is demonstrated in most natural populations which suggests that populations are dispatched from their adaptive peaks as a result of selection on correlated characters, or conflicting selection between the sexes. We analysed patterns of survival selection in a population of serins (Serinus serinus) outside Barcelona over a period of 13 years. There was directional selection for increased wing length in males and females accompanied by strong disruptive selection on both tail and wing length in males and a selection against a positive correlation between the two characters in males. In females there was directional selection for increased bill width but decreased bill depth, which should be contrasted to the stabilizing selection acting on bill depth in males. There were conflicting selection on the characters within a sex and conflicting selection of the same characters between sexes, which constrain the rate of access to the nearest adaptive peak.     

The Hill-Robertson effect: evolutionary consequences of weak selection and linkage in finite populations

The 'Hill-Robertson (HR) effect' describes that linkage between sites under selection will reduce the overall effectiveness of selection in finite populations. Here we discuss the major concepts associated with the HR effect and present results of computer simulations focusing on the linkage effects generated by multiple sites under weak selection. Most models of linkage and selection forecast differences in effectiveness of selection between chromosomes or chromosomal regions involving a number of genes. The abundance and physical clustering of weakly selected mutations across genomes, however, justify the investigation of HR effects at a very local level and we pay particular attention to linkage effects among selected sites of the same gene. Overall, HR effects caused by weakly selected mutations predict differences in effectiveness of selection between genes that differ in exon-intron structures and across genes. Under this scenario, introns might play an advantageous role reducing intragenic HR effects. Finally, we summarize observations that are consistent with local HR effects in Drosophila, discuss potential consequences on population genetic studies and suggest future lines of research.     

Sex differences in bone loss--an evolutionary perspective on a clinical problem

The dramatic increase in the world's population that has occurred over the past 100 years has come largely through reductions in death due to infectious disease. An epidemiologic transition to a preponderance of deaths due to degenerative conditions such as cardiovascular disease and cancer is occurring in the developing countries as well as in the industrialized ones. In the industrialized countries, demographic profiles now reflect the increased life expectancies of both sexes. However, female life expectancies exceed male by six or more years. Further change in mortality patterns will accompany success in the reduction of the number of mortalities attributable to such degenerative conditions as cardiovascular disease and cancer. In the 21st century, conditions associated with sensescence will be of increasing concern. Adaptive strategies that enhanced reproductive success throughout most of human evolution may now prove detrimental to human health as average life expectancies reach unprecedented length. In this environment, differences in the survival mechanisms deployed by males as opposed to females will become increasingly important.     

The X-files in immunity: sex-based differences predispose immune responses

Despite accumulating evidence in support of sex-based differences in innate and adaptive immune responses, in the susceptibility to infectious diseases and in the prevalence of autoimmune diseases, health research and clinical practice do not address these distinctions, and most research studies of immune responses do not stratify by sex. X-linked genes, hormones and societal context are among the many factors that contribute to disparate immune responses in males and females. It is crucial to address sex-based differences in disease pathogenesis and in the pharmacokinetics and pharmacodynamics of therapeutic medications to provide optimal disease management for both sexes.     

Sex differences in behavioral effects of cannabinoids

This review summarizes the existing literature on sex differences in the effects of cannabinoid drugs on behavior, primarily in the adult rodent. These preclinical studies, taken together with preliminary reports of sex differences in cannabinoid effects in humans, suggest that sex of subject may be an important modulating factor in a variety of cannabinoid effects. When sex differences are found, females are usually more sensitive than males to cannabinoids. Both pharmacokinetic and pharmacodynamic variables may contribute to sex differences in behavioral effects of cannabinoids. Given the significant therapeutic potential of cannabinoid agonists and antagonists--as well as their widespread recreational use--it will be important to determine the reliability and functional significance of, as well as mechanisms underlying sex differences in cannabinoid effects.     

Sex differences in immune defenses and response to parasitism in monarch butterflies

Host susceptibility and patterns of infection are predicted to differ between males and females due to sex-based tradeoffs between the demands of reproduction and costly immune defenses. In this study, we examined immune defenses and the response to experimental infection by a protozoan parasite, Ophryocystis elektroscirrha, in male and female monarch butterflies, Danaus plexippus. We quantified two measures of immunity in late instar larvae: the concentration of circulating hemocytes and mid-gut phenoloxidase activity, and also quantified final parasite loads, body size, longevity, and wing melanism of adult butterflies. Results showed that females had greater average hemocyte counts than males in the absence of infection; males, but not females, showed an increased concentration of hemocytes in the presence of infection. However, higher hemocyte concentrations in larvae were not significantly correlated with lower adult parasite loads, and mid-gut phenoloxidase activity was not significantly associated with hemocyte counts or parasite treatments. Among unparasitized females, greater hemocyte concentrations were costly in terms of reduced body size, but for parasite-treated females, hemocyte concentrations and body size were positively associated. Across all monarchs, unparasitized butterflies showed greater wing melanism (darker forewings) than parasitized monarchs. Overall, this study provides support for differential costs of immune defenses in male and female monarch butterflies, and a negative association between parasite infection and monarch wing melanism.     

Sex, parasites and resistance--an evolutionary approach

Immune systems are among the most diverse biological systems. An evolutionary arms race between hosts and rapidly evolving pathogens is supposed to be a reason for this diversity, and might explain why most eukaryotic hosts and parasites reproduce sexually. In this review, I will focus on possible benefits of sexual reproduction in hosts and parasites, using a model system consisting of a tapeworm and its two intermediate hosts, copepods and sticklebacks. We found that the hermaphroditic tapeworms can increase their infection success by reproducing sexually with a partner (outcrossing), instead of reproducing alone. The defence system of the copepods provides highly specific discrimination of antigenic characteristics of the tapeworms. This supports the finding that tapeworms benefit from outcrossing, but contradicts the conventional notion that the immune system of invertebrates, in contrast to vertebrates, is not able to react with specificity. Finally, sticklebacks seem to benefit from optimal diversity in their specific immune system. Previous studies showed that female sticklebacks prefer mates, which sire offspring with an optimal diversity in the MHC (genes involved in antigen presentation). We now found that these individuals suffer less from tapeworm infection. Furthermore, they are able to reduce the expression of an unspecific immune trait, thereby possibly avoiding harmful side effects of a highly activated, unspecific immune system.     

World-wide variation inDrosophila melanogaster sex pheromone: behavioural effects, genetic bases and potential evolutionary consequences

InDrosophila melanogaster, male wing vibration, a key element of courtship behaviour, is most efficiently induced by a female-specific contact pheromonecis, cis 7,11 heptacosadiene (7, 11 HD), which is the main mature female cuticular hydrocarbon in the CS laboratory strain. A study of 63 strains from around the world revealed that flies from Sub-Saharan Africa and the Caribbean are unique in showing low levels 7,11 HD and high levels of the position isomer 5,9 HD. This difference maps to chromosome III, perhaps indicating a simple genetic control of the 7,11 HD: 5,9 HD ratio. Females from strains with high levels of 7,11 HD showed higher levels of mating and mated more rapidly than females with low levels of 7,11 HD. The results are discussed in light of recent discoveries of genetic differences betweenD. melanogaster strains from Africa and those from elsewhere around the world.     

Sex differences in acetylcholine-induced sweating responses due to physical training

Purpose

The present study examined sex differences in the sweat gland response to acetylcholine (ACh) in physically trained and untrained male and female subjects.

Methods

Sweating responses were induced on the forearm and thigh in resting subjects by ACh iontophoresis using a 10% solution at 2 mA for 5 min at 26°C and 50% relative humidity.

Results

The ACh-induced sweating rate (SR) on the forearm and thigh was greater in physically trained male (P < 0.001 for the forearm and thigh, respectively) and female (P = 0.08 for the forearm, P < 0.001 for the thigh) subjects than in untrained subjects of both sexes. The SR was also significantly greater in physically trained males compared to females at both sites (P < 0.001) and in untrained males compared to females on the thigh (P < 0.02) only, although the degree of difference was greater in trained subjects than in untrained subjects. These sex differences can be attributed to the difference in sweat output per gland rather than the number of activated sweat glands.

Conclusion

We conclude that physical training enhances the ACh-induced SR in both sexes but that the degree of enhancement is greater in male than in female subjects. The effects of physical training and sex on the SR may be due to changes in peripheral sensitivity to ACh and/or sweat gland size.     

Fluctuating selection and its (elusive) evolutionary consequences in a wild rodent population

Temporal fluctuations in the strength and direction of selection are often proposed as a mechanism that slows down evolution, both over geological and contemporary timescales. Both the prevalence of fluctuating selection and its relevance for evolutionary dynamics remain poorly understood however, especially on contemporary timescales: unbiased empirical estimates of variation in selection are scarce, and the question of how much of the variation in selection translates into variation in genetic change has largely been ignored. Using long‐term individual‐based data for a wild rodent population, we quantify the magnitude of fluctuating selection on body size. Subsequently, we estimate the evolutionary dynamics of size and test for a link between fluctuating selection and evolution. We show that, over the past 11 years, phenotypic selection on body size has fluctuated significantly. However, the strength and direction of genetic change have remained largely constant over the study period; that is, the rate of genetic change was similar in years where selection favoured heavier vs. lighter individuals. This result suggests that over shorter timescales, fluctuating selection does not necessarily translate into fluctuating evolution. Importantly however, individual‐based simulations show that the correlation between fluctuating selection and fluctuating evolution can be obscured by the effect of drift, and that substantially more data are required for a precise and accurate estimate of this correlation. We identify new challenges in measuring the coupling between selection and evolution, and provide methods and guidelines to overcome them.