Multi-locus approaches for the measurement of selection on correlated genetic loci

The study of ecological speciation is inherently linked to the study of selection. Methods for estimating phenotypic selection within a generation based on associations between trait values and fitness (e.g., survival) of individuals are established. These methods attempt to disentangle selection acting directly on a trait from indirect selection caused by correlations with other traits via multivariate statistical approaches (i.e., inference of selection gradients). The estimation of selection on genotypic or genomic variation could also benefit from disentangling direct and indirect selection on genetic loci. However, achieving this goal is difficult with genomic data because the number of potentially correlated genetic loci (p) is very large relative to the number of individuals sampled (n). In other words, the number of model parameters exceeds the number of observations (p ≫ n). We present simulations examining the utility of whole genome regression approaches (i.e., Bayesian sparse linear mixed models) for quantifying direct selection in cases where p ≫ n. Such models have been used for genome-wide association mapping and are common in artificial breeding. Our results show they hold promise for studies of natural selection in the wild, and thus of ecological speciation. But we also demonstrate important limitations to the approach and discuss study designs required for more robust inferences

The genetics of mate preferences in hybrids between two young and sympatric Lake Victoria cichlid species

The genetic architecture of mate preferences is likely to affect significant evolutionary processes, including speciation and hybridization. Here, we investigate laboratory hybrids between a pair of sympatric Lake Victoria cichlid fish species that appear to have recently evolved from a hybrid population between similar predecessor species. The species demonstrate strong assortative mating in the laboratory, associated with divergent male breeding coloration (red dorsum versus blue). We show in a common garden experiment, using DNA-based paternity testing, that the strong female mate preferences among males of the two species are fully recovered in a large fraction of their F2 hybrid generation. Individual hybrid females often demonstrated consistent preferences in multiple mate choice trials (more than or equal to five) across a year or more. This result suggests that female mate preference is influenced by relatively few major genes or genomic regions. These preferences were not changed by experience of a successful spawning event with a male of the non-preferred species in a no-choice single-male trial. We found no evidence for imprinting in the F2 hybrids, although the F1 hybrid females may have been imprinted on their mothers. We discuss this nearly Mendelian inheritance of consistent innate mate preferences in the context of speciation theory

The relative contribution of genes and environment to alcohol use in early adolescents: Are similar factors related to initiation of alcohol use and frequency of drinking?

Item does not contain fulltextBackground: The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual differences in initiation of alcohol use and frequency of drinking. Methods: Questionnaire data collected by the Netherlands Twin Register were available for 694 twin pairs aged of 12 to 15 years. Bivariate genetic model fitting analyses were conducted inmx. We modeled the variance of initiation of alcohol use and frequency of drinking as a function of three influences: genetic effects, common environmental effects, and unique environmental effects. Analyses were performed conditional on sex. Results: Findings indicated that genetic factors were most important for variation in early initiation of alcohol use (83% explained variance in males and 70% in females). There was a small contribution of common environment (2% in males, 19% in females). In contrast, common environmental factors explained most of the variation in frequency of drinking (82% in males and females). In males the association between initiation and frequency was explained by common environmental factors influencing both phenotypes. In females, there was a large contribution of common environmental factors that influenced frequency of drinking only. There was no evidence that different genetic or common environmental factors operated in males and females. Conclusion: Different factors were involved in individual differences in early initiation of alcohol use and frequency of drinking once adolescents have started to use alcohol

Understanding local ethnic inequalities in childhood BMI through cross-sectional analysis of routinely collected local data

Background: Local-level analysis of ethnic inequalities in health is lacking, prohibiting a comprehensive understanding of the health needs of local populations and the design of effective health services. Knowledge of ethnic disparities in child weight status is particularly limited by overlooking both the heterogeneity within ethnic groupings; and the complex ecological contexts in which obesity arises. This study aimed to establish whether there was variation in childhood BMI across ethnic groups in Coventry, and the influence of individual, school and neighbourhood contexts, using routinely collected local data. Methods: National Child Measurement Programme data were compiled for the period 2007/8-2014/15 and combined with routinely collected local data reflecting school performance and demographics, and school and neighbourhood physical environments. Multi-level modelling using Monte Carlo Markov Chain methods was used to account for the clustering of children within schools and neighbourhoods. Ethnic group differences in BMI z-score (zBMI) were explored at 4-5 years and 10-11 years for girls and boys alongside individual, school and neighbourhood covariates. Results: At age 4-5 years (n = 28,407), ethnic group differences were similar for boys and girls, with children from South Asian, White other, Chinese and 'any other' ethnic groups having a significantly lower zBMI, and Black African children having a higher zBMI, versus White British (WB) children. Patterns differed considerably at age 10-11 years (n = 25,763) with marked sex differences. Boys from White other, Bangladeshi and Black African groups had a significantly higher zBMI than WB boys. For girls, only children from Black ethnic groups showed a significantly higher zBMI. Area-level deprivation was the only important school or neighbourhood covariate, but its inclusion did not explain ethnic group differences in child zBMI. Conclusion: This analysis contributes to the existing literature by identifying nuanced patterns of ethnic disparities in childhood adiposity in Coventry, supporting the targeting of early obesity prevention for children from Black African groups, as well as girls from Black Caribbean and Black other ethnic backgrounds; and boys from Bangladeshi and White other ethnic backgrounds. It also demonstrates the utility of exploring routinely collected local data sets in building a comprehensive understanding of local population needs.</p

The Familial Clustering of Age at Menarche in Extended Twin Families

The timing of puberty is complex, possibly involving many genetic factors that may interact with environmental influences. Familial resemblance for age at menarche was studied in a sample of 4,995 female twins, 1,296 sisters, 2,946 mothers and 635 female spouses of male twins. They had indicated their age at menarche as part of a larger longitudinal survey. We assessed assortative mating for age at menarche, gene–environment interaction effects and estimated the heritability of individual differences in pubertal timing. There was significant evidence of gene–environment interaction, accounting for 1.5% of the variance. There was no indication of consistent mate assortment on age at menarche. Individual differences in age at menarche are highly heritable, with additive genetic factors explaining at least 70% of the true variation. An additional 1.5% of the variation can be explained by a genotype–environment interaction effect where environmental factors are more important in individuals genetically predisposed for late menarche

Regulatory control and the costs and benefits of biochemical noise

Experiments in recent years have vividly demonstrated that gene expression can be highly stochastic. How protein concentration fluctuations affect the growth rate of a population of cells, is, however, a wide open question. We present a mathematical model that makes it possible to quantify the effect of protein concentration fluctuations on the growth rate of a population of genetically identical cells. The model predicts that the population's growth rate depends on how the growth rate of a single cell varies with protein concentration, the variance of the protein concentration fluctuations, and the correlation time of these fluctuations. The model also predicts that when the average concentration of a protein is close to the value that maximizes the growth rate, fluctuations in its concentration always reduce the growth rate. However, when the average protein concentration deviates sufficiently from the optimal level, fluctuations can enhance the growth rate of the population, even when the growth rate of a cell depends linearly on the protein concentration. The model also shows that the ensemble or population average of a quantity, such as the average protein expression level or its variance, is in general not equal to its time average as obtained from tracing a single cell and its descendants. We apply our model to perform a cost-benefit analysis of gene regulatory control. Our analysis predicts that the optimal expression level of a gene regulatory protein is determined by the trade-off between the cost of synthesizing the regulatory protein and the benefit of minimizing the fluctuations in the expression of its target gene. We discuss possible experiments that could test our predictions.Comment: Revised manuscript;35 pages, 4 figures, REVTeX4; to appear in PLoS Computational Biolog

Negative phenotypic and genetic associations between copulation duration and longevity in male seed beetles

Reproduction can be costly and is predicted to trade-off against other characters. However, while these trade-offs are well documented for females, there has been less focus on aspects of male reproduction. Furthermore, those studies that have looked at males typically only investigate phenotypic associations, with the underlying genetics often ignored. Here, we report on phenotypic and genetic trade-offs in male reproductive effort in the seed beetle, Callosobruchus maculatus. We find that the duration of a male's first copulation is negatively associated with subsequent male survival, phenotypically and genetically. Our results are consistent with life-history theory and suggest that like females, males trade-off reproductive effort against longevity

Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy