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PURPOSE: There is an urgent need to understand the biological factors contributing to the racial survival disparity among women with hormone receptor-positive (HR+), HER2− breast cancer. In this study, we examined the impact of PAM50 subtype on 10-year mortality rate in women with HR+, HER2− breast cancer by race. METHODS: Women with localized, HR+, HER2− breast cancer diagnosed between 2002 to 2012 from two population-based cohorts were evaluated. Archival tumors were obtained and classified by PAM50 into four molecular subtypes (i.e., luminal A, luminal B, HER2-enriched, and basal-like). The molecular subtypes within HR+, HER2− breast cancers and corresponding 10-year mortality rate were compared between Black and Non-Hispanic White (NHW) women using Cox proportional hazard ratios and survival analysis, adjusting for covariates. RESULTS: In this study, 318 women with localized, HR+, HER2− breast cancer were included—227 Black (71%) and 91 NHW (29%). Young Black women (age≤50) had the highest proportion of HR+,non-luminal A tumors (47%), compared to young NHW (10%), older Black women (31%), and older NHW (30%). Overall, women with HR+,non-luminal A subtypes had a higher 10-year mortality rate compared to HR+, luminal A subtypes after adjustment for age, stage and income (HR 4.21 for Blacks, 95% CI=1.74–10.18 and HR 3.44 for NHW, 95% CI=1.31–9.03). Among HR+, non-luminal A subtypes there was however no significant racial difference in 10-yr mortality observed (Black vs. NHW: HR 1.23, 95% CI=0.58–2.58). CONCLUSION: Molecular subtype classification highlights racial disparities in PAM50 subtype distribution among women with HR+, HER2− breast cancer. Among women with HR+, HER2− breast cancer, racial survival disparities are ameliorated after adjusting for molecular subtype.

Few studies have simultaneously compared ageing within genetically similar populations in both laboratory and natural environments. Such comparisons are important for interpreting laboratory studies, because factors such as diet could affect ageing in environment-dependent ways. Using a natural population of antler flies (Protopiophila litigata), we conducted separate factorial experiments in 2012 and 2013 that compared age-specific male survival and mating success in laboratory cages versus a natural field environment while supplementing their diets with protein or sugar. We found consistent and substantial increases in both survival and mating rates in the laboratory compared to the field, but remarkably, despite these large differences actuarial ageing was only higher in the laboratory than in the field in 2012 and similar in the two environments in 2013. In both years, there was no difference between environments in reproductive ageing. We found that males fed protein had a higher mortality rate than males fed sugar (strong and low support in 2012 and 2013, respectively). In contrast, diet did not strongly impact average mating rates, actuarial ageing or reproductive ageing in either experiment. Our results provide the first evidence that the negative effect of protein on life span reported in many laboratory studies can also occur in wild populations, although perhaps less consistently. They also highlight how laboratory environments can influence life-history traits and suggest caution when extrapolating from the laboratory to the field.

High-quality developmental environments often improve individual performance into adulthood, but allocating toward early life traits, such as growth, development rate and reproduction, may lead to trade-offs with late-life performance. It is, therefore, uncertain how a rich developmental environment will affect the ageing process (senescence), particularly in wild insects. To investigate the effects of early life environmental quality on insect life-history traits, including senescence, we reared larval antler flies ( Protopiophila litigata ) on four diets of varying nutrient concentration, then recorded survival and mating success of adult males released in the wild. Declining diet quality was associated with slower development, but had no effect on other life-history traits once development time was accounted for. Fast-developing males were larger and lived longer, but experienced more rapid senescence in survival and lower average mating rate compared to slow developers. Ultimately, larval diet, development time and body size did not predict lifetime mating success. Thus, a rich environment led to a mixture of apparent benefits and costs, mediated by development time. Our results indicate that ‘silver spoon' effects can be complex and that development time mediates the response of adult life-history traits to early life environmental quality.

Dietary restriction (DR) is a well-established intervention to extend lifespan across taxa. Recent studies suggest that DR-driven lifespan extension can be cost-free, calling into question a central tenant of the evolutionary theory of aging. Nevertheless, boosting parental longevity can reduce offspring fitness. Such intergenerational trade-offs are often ignored but can account for the “missing costs” of longevity. Here, we use the nematode Caenorhabditis remanei to test for effects of DR by fasting on fitness of females and their offspring. Females deprived of food for 6 days indeed had increased fecundity, survival, and stress resistance after re-exposure to food compared with their counterparts with constant food access. However, offspring of DR mothers had reduced early and lifetime fecundity, slower growth rate, and smaller body size at sexual maturity. These findings support the direct trade-off between investment in soma and gametes challenging the hypothesis that increased somatic maintenance and impaired reproduction can be decoupled.

Reproduction between individuals from different ancestral populations creates genetically admixed offspring. Admixture can have positive and negative impacts on individual health, feeding back to population health. Historical and forced migrations, and recent mobility, have brought formerly disparate populations of humans together. Here we sought to better understand how temporal changes in genetic admixture influence levels of heterozygosity and health outcomes. We evaluated variation in ancestry over 100 birth years in 35,842 individuals from a genetic database linked to health records in a population in the Southeastern United States. Analysis of 2,678 ancestrally informative markers revealed increased admixture and heterozygosity for all clinically-defined race groups since 1990. Most groups also exhibited increasing long-range linkage disequilibrium over time. A phenome-wide association study of clinical outcomes detected protective associations with female reproductive disorders and increased risk for diseases with links to autoimmunity dysfunction. These mixed effects have important ramifications for human health.

Dietary restriction (DR) is a well-established intervention to extend lifespan across taxa. Recent studies suggest that DR-driven lifespan extension can be cost-free, calling into question a central tenant of the evolutionary theory of ageing. Nevertheless, boosting parental longevity can reduce offspring fitness. Such intergenerational trade-offs are often ignored but can account for the ‘missing costs’ of longevity. Here, we use the nematode Caenorhabditis remanei to test for effects of DR by fasting on fitness of females and their offspring. Females deprived of food for six days indeed had increased fecundity, survival and stress resistance after re-exposure to food compared to their counterparts with constant food access. However, offspring of DR mothers had reduced early and lifetime fecundity, slower growth rate, and smaller body size at sexual maturity. These findings support the direct trade-off between investment in soma and gametes challenging the hypothesis that increased somatic maintenance and impaired reproduction can be decoupled.

International audience; In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

Females can benefit from mate choice for male traits (e.g. sexual ornaments or body condition) that reliably signal the effect that mating will have on mean offspring fitness. These male-derived benefits can be due to material and/or genetic effects. The latter include an increase in the attractiveness, hence likely mating success, of sons. Females can potentially enhance any sex-biased benefits of mating with certain males by adjusting the offspring sex ratio depending on their mate's phenotype. One hypothesis is that females should produce mainly sons when mating with more attractive or higher quality males. Here we perform a meta-analysis of the empirical literature that has accumulated to test this hypothesis. The mean effect size was small (r = 0.064-0.095; i.e. explaining

Evolutionary theory of ageing maintains that increased allocation to early-life reproduction results in reduced somatic maintenance, which is predicted to compromise longevity and late-life reproduction. This prediction has been challenged by the discovery of long-lived mutants with no loss of fecundity. The first such long-lived mutant was found in the nematode worm Caenorhabditis elegans . Specifically, partial loss-of-function mutation in the age-1 gene, involved in the nutrient-sensing insulin/insulin-like growth factor signalling pathway, confers longevity, as well as increased resistance to pathogens and to temperature stress without appreciable fitness detriment. Here, we show that the long-lived age-1 ( hx546 ) mutant has reduced fecundity and offspring production in early-life, but increased fecundity, hatching success, and offspring production in late-life compared with wild-type worms under standard conditions. However, reduced early-life performance of long-lived mutant animals was not fully compensated by improved performance in late-life and resulted in reduced individual fitness. These results suggest that the age-1 ( hx546 ) allele has opposing effects on early-life versus late-life fitness in accordance with antagonistic pleiotropy (AP) and disposable soma theories of ageing. These findings support the theoretical conjecture that experimental studies based on standing genetic variation underestimate the importance of AP in the evolution of ageing.

There are two reasons why researchers are interested in the phenotypic relationship between the expression of male secondary sexual characters (SSCs) and 'ejaculate quality' (defined as sperm/ejaculate traits that are widely assumed to increase female fertility and/or sperm competitiveness). First, if the relationship is positive then females could gain a direct benefit by choosing more attractive males for fertility assurance reasons ('the phenotype-linked fertility' hypothesis). Second, there is much interest in the direction of the correlation between traits favoured by pre-copulatory sexual selection (i.e. affecting mating success) and those favoured by post-copulatory sexual selection (i.e. increasing sperm competitiveness). If the relationship is negative this could lead to the two forms of selection counteracting each other. Theory predicts that the direction of the relationship could be either positive or negative depending on the underlying genetic variance and covariance in each trait, the extent of variation among males in condition (resources available to allocate to reproductive traits), and variation among males in the cost or rate of mating. We conducted a meta-analysis to determine the average relationship between the expression of behavioural and morphological male secondary sexual characters and four assays of ejaculate quality (sperm number, viability, swimming speed and size). Regardless of how the data were partitioned the mean relationship was consistently positive, but always statistically non-significant. The only exception was that secondary sexual character expression was weakly but significantly positively correlated with sperm viability (r = 0.07, P < 0.05). There was no significant difference in the strength or direction of the relationship between behavioural and morphological SSCs, nor among relationships using the four ejaculate quality assays. The implications of our findings are discussed.

The consequences of polyandry for female fitness are controversial. Sexual conflict studies and a meta-analysis of mating rates in insects suggest that there is a longevity cost when females mate repeatedly. Even so, compensatory material benefits can elevate egg production and fertility, partly because polyandry ensures an adequate sperm supply. Polyandry can therefore confer direct benefits. The main controversy surrounds genetic benefits. The argument is analogous to that surrounding the evolution of conventional female mate choice, except that with polyandry it is post-copulatory mechanisms that might bias paternity towards males with higher breeding values for fitness. Recent meta-analyses of extra-pair copulations in birds have cast doubt on whether detectable genetic benefits exist. By contrast, another meta-analysis showed that polyandry elevates egg hatching success (possibly due to a fertilization bias towards sperm with paternal genes that elevate embryo survival) in insects. A detailed summary of whether polyandry elevates other components of offspring performance is lacking. Here we present a comprehensive meta-analysis of 232 effect sizes from 46 experimental studies. These experiments were specifically designed to try to quantify the potential genetic benefits of polyandry by controlling fully for the number of matings by females assigned to monandry and polyandry treatments. The bias-corrected 95% confidence intervals for egg hatching success (d = -0.01 to 0.61), clutch production (d = 0.07 to 0.45) and fertility (d = 0.04 to 0.40) all suggest that polyandry has a beneficial effect (although P values from parametric tests were marginally non-significant at P = 0.075, 0.052 and 0.058, respectively). Polyandry was not significantly beneficial for any single offspring performance trait (e.g. growth rate, survival, adult size), but the test power was low due to small sample sizes (suggesting that many more studies are still needed). We then calculated a composite effect size that provides an index of general offspring performance. Depending on the model assumptions, the mean effect of polyandry was either significantly positive or marginally non-significant. A possible role for publication bias is discussed. The magnitude of the reported potential genetic benefits (d = 0.07 to 0.19) are larger than those from two recent meta-analyses comparing offspring sired by social and extra-pair mates in birds (d = 0.02 to 0.04). This difference raises the intriguing possibility that cryptic, post-copulatory female choice might be more likely to generate 'good gene' or 'compatible gene' benefits than female choice of mates based on the expression of secondary sexual traits.

Recent studies suggest that males might respond in an adaptive manner to an elevated likelihood of male–male competition for mates by facultatively altering their mating preferences. Little is known, however, about how male choice is influenced by a male’s relative competitiveness or by the risk posed by increased physical competition for access to mates compared with greater risk of sperm competition. We investigated how the relative size and presence of a competitor influences male choice using 2-choice experiments in the mosquito fish, Gambusia holbrooki. We varied the size of the focal male, the size of a competitor, and whether the competitor remained alongside the preferred female (physical and sperm competition) or was removed (only greater sperm competition). Prior to viewing a competitor, males, regardless of size, significantly preferred larger females. After a male had viewed a competitor alongside his preferred female, however, he subsequently spent significantly less time associating with her. This change in male choice was not influenced by focal male size, competitor size, or whether or not the competitor was physically present during the choice trial. After viewing a competitor, however, larger males spent significantly more time than did smaller males near their preferred female. Our results suggest that male mating preferences are sensitive to the risk of increased physical or indirect sperm competition, but there was no evidence that males adjust their mate choice in response to the relative size (and therefore presumed competitiveness) of rivals. Key words: competition, direct costs, indirect costs, male mate choice, mosquito fish. [Behav Ecol]

Males of many species defend resources to attract females. Surprisingly, defense of multiple female breeding sites (e.g., nests or burrows) appears to be rare, primarily reported in fish and birds. In fiddler crabs, burrows are a vital resource for reproduction and survival. Both sexes defend individual territories centered on a single burrow. We examined burrow acquisition and defense in Uca capricornis to test whether males defend multiple burrows as a novel strategy to acquire additional mates. When crabs were experimentally forced to acquire a new burrow, females often settled into an empty burrow near resident males. We documented more empty burrows around males than expected by chance and, in addition, larger males had a greater proportion of empty burrows in their immediate vicinity. We experimentally introduced crabs into empty burrows next to focal males: newly introduced males were soon evicted, whereas females were courted and stayed. These results suggest that male U. capricornis defend empty burrows as a strategy to obtain more mates. Intriguingly, however, U. capricornis tend to occur in socially monogamous pairs. This raises the possibility of sexual conflict within social pairs over the presence of additional females and that female‐ female competition might constrain male mating success. Key words: mating systems, polygamy, resource-holding potential, resource monopolization, sexual conflict, sexual selection. [Behav Ecol]

Sexual selection is a major force behind the rapid evolution of male genital morphology among species. Most within-species studies have focused on sexual selection on male genital traits owing to events during or after copulation that increase a male's share of paternity. Very little attention has been given to whether genitalia are visual signals that cause males to vary in their attractiveness to females and are therefore under pre-copulatory sexual selection. Here we show that, on average, female eastern mosquitofish Gambusia holbrooki spent more time in association with males who received only a slight reduction in the length of the intromittent organ (‘gonopodium’) than males that received a greater reduction. This preference was, however, only expressed when females chose between two large males; for small males, there was no effect of genital size on female association time.

Female crickets can exert post-copulatory mating preferences by prematurely removing a male's spermatophore after copulation, which terminates sperm transfer. Although most models of sexual selection assume that female mating preferences are heritable, there has been little work addressing genetic variation underlying post-copulatory mate choice. We used a paternal half-sib design, in which different males were randomly assigned as mates to several females to create half-sib families, to determine the heritability of spermatophore retention time in female house crickets, Acheta domesticus. There was significant additive genetic variance in the timing of spermatophore removal by females [h(2) = 0.50 +/- 0.19 (+/- SE)], suggesting that the timing of spermatophore removal is determined, in part, by the female's own genotype independent of the quality of her mate. The relatively high heritability of spermatophore retention time may be reflective of the absence of strong selection on this trait, consistent with previous work showing no difference in the fitness of females permitted to freely remove the spermatophore of their mates and those forced to accept complete ejaculates.

Although females’ mating preferences are influenced by male characteristics, there are a number of factors intrinsic to females and unrelated to male phenotype that can modulate female choice. We assessed the effects of age and mating experience on mechanisms of pre- and post-copulatory mate choice in female house crickets, Acheta domesticus L., by randomly assigning males to females, but independently varying the age and number of previous matings of females at the time of experimental matings. Latency to mating, a measure of a female’s pre-copulatory preference, was influenced by female age at the time of mating, with older females mating sooner than younger females. The reduced selectivity of older females appears consistent with life-history theory, which predicts that the reproductive value of females should decline with age. The length of time that females retained the spermatophore after mating, a measure of a female’s post-copulatory mating preference, was not influenced by female age at the time of mating, the number of previous matings, or any interaction between the two main effects. Contrary to previous reports, male mass had no effect on either the latency to mating or female retention of the spermatophore in A. domesticus. We conclude that female age and mating experience can moderate female selectivity, but that their impact varies according to the mechanism by which females favor particular sires.

There are two reasons why researchers are interested in the phenotypic relationship between the expression of male secondary sexual characters (SSCs) and 'ejaculate quality' (defined as sperm/ejaculate traits that are widely assumed to increase female fertility and/or sperm competitiveness). First, if the relationship is positive then females could gain a direct benefit by choosing more attractive males for fertility assurance reasons ('the phenotype-linked fertility' hypothesis). Second, there is much interest in the direction of the correlation between traits favoured by pre-copulatory sexual selection (i.e. affecting mating success) and those favoured by post-copulatory sexual selection (i.e. increasing sperm competitiveness). If the relationship is negative this could lead to the two forms of selection counteracting each other. Theory predicts that the direction of the relationship could be either positive or negative depending on the underlying genetic variance and covariance in each trait, the extent of variation among males in condition (resources available to allocate to reproductive traits), and variation among males in the cost or rate of mating. We conducted a meta-analysis to determine the average relationship between the expression of behavioural and morphological male secondary sexual characters and four assays of ejaculate quality (sperm number, viability, swimming speed and size). Regardless of how the data were partitioned the mean relationship was consistently positive, but always statistically non-significant. The only exception was that secondary sexual character expression was weakly but significantly positively correlated with sperm viability (r = 0.07, P0.05). There was no significant difference in the strength or direction of the relationship between behavioural and morphological SSCs, nor among relationships using the four ejaculate quality assays. The implications of our findings are discussed.

Compelling evidence from many animal taxa indicates that male genitalia are often under postcopulatory sexual selection for characteristics that increase a male’s relative fertilization success. There could, however, also be direct precopulatory female mate choice based on male genital traits. Before clothing, the nonretractable human penis would have been conspicuous to potential mates. This observation has generated suggestions that human penis size partly evolved because of female choice. Here we show, based upon female assessment of digitally projected life-size, computer-generated images, that penis size interacts with body shape and height to determine male sexual attractiveness. Positive linear selection was detected for penis size, but the marginal increase in attractiveness eventually declined with greater penis size (i.e., quadratic selection). Penis size had a stronger effect on attractiveness in taller men than in shorter men. There was a similar increase in the positive effect of penis size on attractiveness with a more masculine body shape (i.e., greater shoulder-to-hip ratio). Surprisingly, larger penis size and greater height had almost equivalent positive effects on male attractiveness. Our results support the hypothesis that female mate choice could have driven the evolution of larger penises in humans. More broadly, our results show that precopulatory sexual selection can play a role in the evolution of genital traits.