Male mutation bias and possible long-term effects of human activities.

The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population

The MHC and body odors: arbitrary effects caused by shifts of mean pleasantness

The main conclusions of the study by Jacob et al.1 published in February's issue of Nature Genetics differ from those of most previous studies of the major histocompatibility complex (MHC) and mate or odor preference in any animal2. It is therefore important to understand what may have caused these differences

Embryo survival in the oviduct not significantly influenced by major histocompatibility complex social signaling in the horse.

The major histocompatibility complex (MHC) influences sexual selection in various vertebrates. Recently, MHC-linked social signaling was also shown to influence female fertility in horses (Equus caballus) diagnosed 17 days after fertilization. However, it remained unclear at which stage the pregnancy was terminated. Here we test if MHC-linked cryptic female choice in horses happens during the first days of pregnancy, i.e., until shortly after embryonic entrance into the uterus and before fixation in the endometrium. We exposed estrous mares to one of several unrelated stallions, instrumentally inseminated them with semen of another stallion, and flushed the uterus 8 days later to test for the presence of embryos. In total 68 embryos could be collected from 97 experimental trials. This success rate of 70.1% was significantly different from the mean pregnancy rate of 45.7% observed 17 days after fertilization using the same experimental protocol but without embryo flushing. Embryo recovery rate was not significantly dependent on whether the mares had been socially exposed to an MHC-dissimilar or an MHC-similar stallion. These observations suggest that MHC-linked maternal strategies affect embryo survival mainly (or only) during the time of fixation in the uterus

MHC-correlated preferences in diestrous female horses (Equus caballus).

Genes of the major histocompatibility complex (MHC) have been shown to influence communication in many vertebrates, possibly with context-specific MHC-correlated reactions. Here we test for MHC-linked female preferences in the polygynous horse (Equus caballus) by repeatedly exposing 19 mares to a group of seven sexually experienced stallions. Each mare was tested four times during two consecutive reproductive cycles, twice during estrus and twice during diestrus. Male plasma testosterone concentrations were determined from weekly blood samples, and equine leukocyte antigen (ELA) class I and II alleles were determined serologically at the end of the experiments. Perception of male attractiveness was strongly dependent on estrous cycle: mean preference scores did not correlate for mares in diestrus and estrus and varied more during estrus than during diestrus. We found elevated female interests for MHC-dissimilar stallions, but only during diestrus, not during estrus. Female preferences were not significantly predicted by mean male testosterone plasma concentrations. However, testosterone concentrations changed during the 11 weeks of the experiment. By the end of the experiment, average testosterone concentration was significantly correlated to the average number of MHC alleles the stallions shared with the mares. We conclude that the MHC affects female preferences for stallions, but non-MHC linked male characteristics can overshadow effects of the MHC during estrus

Optimization of crystal nucleation close to a metastable fluid-fluid phase transition

The presence of a metastable fluid-fluid critical point is thought to dramatically influence the crystallization pathway, increasing the nucleation rate by many orders of magnitude over the predictions of classical nucleation theory. We use molecular dynamics simulations to study the kinetics of crystallization in the vicinity of this metastable critical point and throughout the metastable fluid-fluid phase diagram. To quantitatively understand how the fluid-fluid phase separation affects the crystal nucleation, we evaluate accurately the kinetics and reconstruct the thermodynamic free-energy landscape of crystal formation. Contrary to expectations, we find no special advantage of the proximity of the metastable critical point on the crystallization rates. However, we find that the ultrafast formation of a dense liquid phase causes the crystallization to accelerate both near the metastable critical point and almost everywhere below the fluid-fluid spinodal line. These results unveil three different scenarios for crystallization that could guide the optimization of the process in experiments

Occurrence and Risk Factors for New Dependency on Chronic Care, Respiratory Support, Dialysis and Mortality in the First Year After Sepsis

Sepsis survival is associated with adverse outcomes. Knowledge about risk factors for adverse outcomes is lacking. We performed a population-based cohort study of 116,507 survivors of hospital-treated sepsis identified in health claims data of a German health insurance provider. We determined the development and risk factors for long-term adverse events: new dependency on chronic care, chronic dialysis, long-term respiratory support, and 12-month mortality. At-risk patients were defined by absence of these conditions prior to sepsis. Risk factors were identified using simple and multivariable logistic regression analyses. In the first year post-sepsis, 48.9% (56,957) of survivors had one or more adverse outcome, including new dependency on chronic care (31.9%), dialysis (2.8%) or respiratory support (1.6%), and death (30.7%). While pre-existing comorbidities adversely affected all studied outcomes (>4 comorbidities: OR 3.2 for chronic care, OR 4.9 for dialysis, OR 2.7 for respiratory support, OR 4.7 for 12-month mortality), increased age increased the odds for chronic care dependency and 12-month mortality, but not for dialysis or respiratory support. Hospital-acquired and multi-resistant infections were associated with increased risk of chronic care dependency, dialysis, and 12-month mortality. Multi-resistant infections also increased the odds of respiratory support. Urinary or respiratory infections or organ dysfunction increased the odds of new dialysis or respiratory support, respectively. Central nervous system infection and organ dysfunction had the highest OR for chronic care dependency among all infections and organ dysfunctions. Our results imply that patient- and infection-related factors have a differential impact on adverse life changing outcomes after sepsis. There is an urgent need for targeted interventions to reduce the risk

Sex differentiation in grayling (Salmonidae) goes through an all-male stage and is delayed in genetic males who instead grow faster.

Fish populations can be threatened by distorted sex ratios that arise during sex differentiation. Here we describe sex differentiation in a wild grayling (Thymallus thymallus) population that suffers from distorted sex ratios. We verified that sex determination is linked to the sex determining locus (sdY) of salmonids. This allowed us to study sex-specific gene expression and gonadal development. Sex-specific gene expression could be observed during embryogenesis and was strong around hatching. About half of the fish showed immature testes around eleven weeks after fertilization. This phenotype was mostly replaced by the "testis-to-ovary" or "ovaries" phenotypes during development. The gonads of the remaining fish stayed undifferentiated until six months after fertilization. Genetic sexing revealed that fish with undifferentiated gonads were all males, who grew larger than the genetic females during the observational period. Only 12% of the genetic males showed testicular tissue six months after fertilization. We conclude that sex differentiation starts before hatching, goes through an all-male stage for both sexes (which represents a rare case of "undifferentiated" gonochoristic species that usually go through an all-female stage), and is delayed in males. During these juvenile stages males grow faster than females instead of developing their gonads

Pathogen-induced hatching and population-specific life-history response to water-borne cues in brown trout (Salmo trutta)

Hatching is an important niche shift, and embryos in a wide range of taxa can either accelerate or delay this life-history switch in order to avoid stage-specific risks. Such behavior can occur in response to stress itself and to chemical cues that allow anticipation of stress. We studied the genetic organization of this phenotypic plasticity and tested whether there are differences among populations and across environments in order to learn more about the evolutionary potential of stress-induced hatching. As a study species, we chose the brown trout (Salmo trutta; Salmonidae). Gametes were collected from five natural populations (within one river network) and used for full-factorial in vitro fertilizations. The resulting embryos were either directly infected with Pseudomonas fluorescens or were exposed to waterborne cues from P. fluorescens-infected conspecifics. We found that direct inoculation with P. fluorescens increased embryonic mortality and induced hatching in all host populations. Exposure to waterborne cues revealed population-specific responses. We found significant additive genetic variation for hatching time, and genetic variation in trait plasticity. In conclusion, hatching is induced in response to infection and can be affected by waterborne cues of infection, but populations and families differ in their reaction to the latter

Is Mate Choice in Humans MHC-Dependent?

In several species, including rodents and fish, it has been shown that the Major Histocompatibility Complex (MHC) influences mating preferences and, in some cases, that this may be mediated by preferences based on body odour. In humans, the picture has been less clear. Several studies have reported a tendency for humans to prefer MHC-dissimilar mates, a sexual selection that would favour the production of MHC-heterozygous offspring, who would be more resistant to pathogens, but these results are unsupported by other studies. Here, we report analyses of genome-wide genotype data (from the HapMap II dataset) and HLA types in African and European American couples to test whether humans tend to choose MHC-dissimilar mates. In order to distinguish MHC-specific effects from genome-wide effects, the pattern of similarity in the MHC region is compared to the pattern in the rest of the genome. African spouses show no significant pattern of similarity/dissimilarity across the MHC region (relatedness coefficient, R = 0.015, p = 0.23), whereas across the genome, they are more similar than random pairs of individuals (genome-wide R = 0.00185, p<10−3). We discuss several explanations for these observations, including demographic effects. On the other hand, the sampled European American couples are significantly more MHC-dissimilar than random pairs of individuals (R = −0.043, p = 0.015), and this pattern of dissimilarity is extreme when compared to the rest of the genome, both globally (genome-wide R = −0.00016, p = 0.739) and when broken into windows having the same length and recombination rate as the MHC (only nine genomic regions exhibit a higher level of genetic dissimilarity between spouses than does the MHC). This study thus supports the hypothesis that the MHC influences mate choice in some human populations