Environmental and Genetic Contributions to Imperfect wMel-Like Wolbachia Transmission and Frequency Variation.
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ABSTRACT: Maternally transmitted Wolbachia bacteria infect about half of all insect species. They usually show imperfect maternal transmission and often produce cytoplasmic incompatibility (CI). Irrespective of CI, Wolbachia frequencies tend to increase when rare only if they benefit host fitness. Several Wolbachia, including wMel that infects Drosophila melanogaster, cause weak or no CI and persist at intermediate frequencies. On the island of São Tomé off West Africa, the frequencies of wMel-like Wolbachia infecting Drosophila yakuba (wYak) and Drosophila santomea (wSan) fluctuate, and the contributions of imperfect maternal transmission, fitness effects, and CI to these fluctuations are unknown. We demonstrate spatial variation in wYak frequency and transmission on São Tomé. Concurrent field estimates of imperfect maternal transmission do not predict spatial variation in wYak frequencies, which are highest at high altitudes where maternal transmission is the most imperfect. Genomic and genetic analyses provide little support for D. yakuba effects on wYak transmission. Instead, rearing at cool temperatures reduces wYak titer and increases imperfect transmission to levels observed on São Tomé. Using mathematical models of Wolbachia frequency dynamics and equilibria, we infer that temporally variable imperfect transmission or spatially variable effects on host fitness and reproduction are required to explain wYak frequencies. In contrast, spatially stable wSan frequencies are plausibly explained by imperfect transmission, modest fitness effects, and weak CI. Our results provide insight into causes of wMel-like frequency variation in divergent hosts. Understanding this variation is crucial to explain Wolbachia spread and to improve wMel biocontrol of human disease in transinfected mosquito systems.
Project description:The development, function, and integration of morphological characteristics are all hypothesized to influence the utility of traits for phylogenetic reconstruction by affecting the way in which morphological characteristics evolve. We use a baboon model to test the hypotheses about phenotypic and quantitative genetic variation of traits in the cranium that bear on a phenotype's propensity to evolve. We test the hypotheses that: 1) individual traits in different functionally and developmentally defined regions of the cranium are differentially environmentally, genetically, and phenotypically variable; 2) genetic covariance with other traits constrains traits in one region of the cranium more than those in others; 3) and regions of the cranium subject to different levels of mechanical strain differ in the magnitude of variation in individual traits. We find that the levels of environmental and genetic variation in individual traits are randomly distributed across regions of the cranium rather than being structured by developmental origin or degree of exposure to strain. Individual traits in the cranial vault tend to be more constrained by covariance with other traits than those in other regions. Traits in regions subject to high degrees of strain during mastication are not any more variable at any level than other traits. If these results are generalizable to other populations, they indicate that there is no reason to suppose that individual traits from any one part of the cranium are intrinsically less useful for reconstructing patterns of evolution than those from any other part.
Project description:The relative contribution of genetic and environmental factors to variation in immune response is still poorly understood. Here, we performed a deep phenotypic analysis of immunological parameters and molecular profiles of laboratory mice released into an outdoor enclosure, carrying genetic susceptibility genes (Nod2 and Atg16l1) implicated in the development of inflammatory bowel diseases. Differences in lymphocyte populations were largely driven by the lab and wild environment. However, cytokine production after stimulation with microbial antigens showed a stronger genetic component in the lab, which was reduced after exposure to the wild environment. Multi-omic models identified key transcriptional factors associated with lymphocyte changes predictive of the environment, as well as sub-networks associated with cytokine responses against Candida albicans and Bacteroides vulgatus. Hence, exposing laboratory mice of different genetic backgrounds to the outdoor environment may identify important contributors to immune variation.
Project description:IntroductionFacial phenotype is influenced by genes and environment; however, little is known about their relative contributions to normal facial morphology. The aim of this study was to assess the relative genetic and environmental contributions to facial morphological variation using a three-dimensional (3D) population-based approach and the classical twin study design.Materials and methods3D facial images of 1380 female twins from the TwinsUK Registry database were used. All faces were landmarked, by manually placing 37 landmark points, and Procrustes registered. Three groups of traits were extracted and analysed: 19 principal components (uPC) and 23 principal components (sPC), derived from the unscaled and scaled landmark configurations respectively, and 1275 linear distances measured between 51 landmarks (37 manually identified and 14 automatically calculated). The intraclass correlation coefficients, rMZ and rDZ, broad-sense heritability (h2), common (c2) and unique (e2) environment contributions were calculated for all traits for the monozygotic (MZ) and dizygotic (DZ) twins.ResultsHeritability of 13 uPC and 17 sPC reached statistical significance, with h2 ranging from 38.8% to 78.5% in the former and 30.5% to 84.8% in the latter group. Also, 1222 distances showed evidence of genetic control. Common environment contributed to one PC in both groups and 53 linear distances (4.3%). Unique environment contributed to 17 uPC and 20 sPC and 1245 distances.ConclusionsGenetic factors can explain more than 70% of the phenotypic facial variation in facial size, nose (width, prominence and height), lips prominence and inter-ocular distance. A few traits have shown potential dominant genetic influence: the prominence and height of the nose, the lower lip prominence in relation to the chin and upper lip philtrum length. Environmental contribution to facial variation seems to be the greatest for the mandibular ramus height and horizontal facial asymmetry.
Project description:The fitness effects associated with Wolbachia infection have wide-ranging ecological and evolutionary consequences for host species. How these effects are modulated by the relative influence of host and Wolbachia genomes has been described as a balancing act of genomic cooperation and conflict. For vertically transmitted symbionts, like cytoplasmic Wolbachia, concordant host-symbiont fitness interests would seem to select for genomic cooperation. However, Wolbachia's ability to manipulate host reproductive systems and distort offspring sex ratios presents an evolutionary conflict of interest with infected hosts. In the parthenogenesis-inducing (PI) form of Wolbachia found in many haplodiploid insects, Wolbachia fitness is realized through females and is enhanced by their feminization of male embryos and subsequent parthenogenetic reproduction. In contrast, as long as Wolbachia is not fixed in a population and sexual reproduction persists, fitness for the host species is realized through both male and female offspring production. How these cooperating and competing interests interact and the relative influence of host and Wolbachia genomes were investigated in the egg parasitoid Trichogramma kaykai, where Wolbachia infection has remained at a low frequency in the field. A factorial design in which laboratory cultures of Wolbachia-infected T. kaykai were cured and re-infected with alternative Wolbachia strains was used to determine the relative influence of host and Wolbachia genomes on host fitness values. Our results suggest fitness variation is largely a function of host genetic background, except in the case of offspring sex ratio where a significant interaction between host and Wolbachia genomes was found. We also find a significant effect associated with the horizontal transfer of Wolbachia strains, which we discuss in terms of the potential for coadaptation in PI-Wolbachia symbioses.
Project description:Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature of this highly addictive drug. Sadly, none of this information has translated into the development of effective therapies for the treatment of cocaine addiction. This review endeavors to assess the current state of cocaine research in an attempt to identify novel pathways for therapeutic development. For example, risk of cocaine addiction is highly heritable but genome-wide analyses comparing cocaine-dependent individuals to controls have not resulted in promising targets for drug development. Is this because the genetics of addiction is too complex or because the existing research methodologies are inadequate? Likewise, animal studies have revealed dozens of enduring changes in gene expression following prolonged exposure to cocaine, none of which have translated into therapeutics either because the resulting compounds were ineffective or produced intolerable side-effects. Recently, attention has focused on epigenetic modifications resulting from repeated cocaine intake, some of which appear to be heritable through changes in the germline. While epigenetic changes represent new vistas for therapeutic development, selective manipulation of epigenetic marks is currently challenging even in animals such that translational potential is a distant prospect. This review will reveal that despite the enormous progress made in understanding the molecular and physiological bases of cocaine addiction, there is much that remains a mystery. Continued advances in genetics and molecular biology hold potential for revealing multiple pathways toward the development of treatments for the continuing scourge of cocaine addiction.
Project description:Genes, sex, age, diet, lifestyle, gut microbiome, and multiple other factors affect human metabolomic profiles. Understanding metabolomic variation is critical in human nutrition research as metabolites that are sensitive to change versus those that are more stable might be more informative for a particular study design. This study aims to identify stable metabolomic regions and determine the genetic and environmental contributions to stability. Using a classic twin design, 1H nuclear magnetic resonance (NMR) urinary metabolomic profiles were measured in 128 twins at baseline, 1 month, and 2 months. Multivariate mixed models identified stable urinary metabolites with intraclass correlation coefficients ≥0.51. Longitudinal twin modeling measured the contribution of genetic and environmental influences to variation in the stable urinary NMR metabolome, comprising stable metabolites. The conservation of an individual's stable urinary NMR metabolome over time was assessed by calculating conservation indices. In this study, 20% of the urinary NMR metabolome is stable over 2 months (intraclass correlation (ICC) 0.51-0.65). Common genetic and shared environmental factors contributed to variance in the stable urinary NMR metabolome over time. Using the stable metabolome, 91% of individuals had good metabolomic conservation indices ≥0.70. To conclude, this research identifies 20% of the urinary NMR metabolome as stable, improves our knowledge of the sources of metabolomic variation over time, and demonstrates the conservation of an individual's urinary NMR metabolome.
Project description:Background: Twin studies indicate that genetic and environmental factors contribute to both psychological resilience and coping style, but estimates of their relative molecular and shared environmental contributions are limited. The degree of overlap in the genetic architectures of these traits is also unclear. Methods: Using data from a large population- and family-based cohort Generation Scotland (N = 8,734), we estimated the genetic and shared environmental variance components for resilience, task-, emotion-, and avoidance-oriented coping style in a linear mixed model (LMM). Bivariate LMM analyses were used to estimate the genetic correlations between these traits. Resilience and coping style were measured using the Brief Resilience Scale and Coping Inventory for Stressful Situations, respectively. Results: The greatest proportion of the phenotypic variance in resilience remained unexplained, although significant contributions from common genetic variants and family-shared environment were found. Both task- and avoidance-oriented coping had significant contributions from common genetic variants, sibling- and couple-shared environments, variance in emotion-oriented coping was attributable to common genetic variants, family- and couple-shared environments. The estimated correlation between resilience and emotion-oriented coping was high for both common-variant-associated genetic effects (r G = -0.79, se = 0.19), and for the additional genetic effects from the pedigree (r K = -0.94, se = 0.30). Genetic correlations between resilience and task- and avoidance-oriented coping did not meet statistical significance. Conclusions: Both genetics and shared environmental effects were major contributing factors to coping style, whilst the variance in resilience remains largely unexplained. Strong genetic overlap between resilience and emotion-oriented coping suggests a relationship whereby genetic factors that increase negative emotionality also lead to decreased resilience. We suggest that genome-wide family-based studies of resilience and coping may help to elucidate tractable methodologies to identify genetic architectures and modifiable environmental risk factors to protect against psychiatric illness, although further work with larger sample sizes is needed.
Project description:BACKGROUND:The variation and covariation for many cardiometabolic traits have been decomposed into genetic and environmental fractions, by using twin or single-nucleotide polymorphism (SNP) models. However, differences in population, age, sex, and other factors hamper the comparison between twin- and SNP-based estimates. METHODS AND RESULTS:Twenty-four cardiometabolic traits and 700,000 genotyped SNPs were available in the study base of 10 682 twins from TwinGene cohort. For the 27 highly correlated pairs (absolute phenotypic correlation coefficient ?0.40), twin-based bivariate structural equation models were performed in 3870 complete twin pairs, and SNP-based bivariate genomic relatedness matrix restricted maximum likelihood methods were performed in 5779 unrelated individuals. In twin models, the model including additive genetic variance and unique/nonshared environmental variance was the best-fitted model for 7 pairs (5 of them were between blood pressure traits); the model including additive genetic variance, common/shared environmental variance, and unique/nonshared environmental variance components was best fitted for 4 pairs, but estimates of shared environment were close to zero; and the model including additive genetic variance, dominant genetic variance, and unique/nonshared environmental variance was best fitted for 16 pairs, in which significant dominant genetic effects were identified for 13 pairs (including all 9 obesity-related pairs). However, SNP models did not identify significant estimates of dominant genetic effects for any pairs. In the paired t test, twin- and SNP-based estimates of additive genetic correlation were not significantly different (both were 0.67 on average), whereas the nonshared environmental correlations from these 2 models differed slightly from each other (on average, twin-based estimate=0.64 and SNP-based estimate=0.68). CONCLUSIONS:Beside additive genetic effects and nonshared environment, nonadditive genetic effects (dominance) also contribute to the covariation between certain cardiometabolic traits (especially for obesity-related pairs); contributions from the shared environment seem to be weak for their covariation in TwinGene samples.
Project description:Translocation is one of the most frequently occurring human chromosomal aberrations. The constitutional t(11;22)(q23;q11), which is the only known recurrent non-Robertsonian translocation, represents a good model for studying translocations in humans. Here we demonstrate polymorphisms of the palindromic sequence at the t(11;22) breakpoint that affect the frequency of de novo translocations in sperm from normal males. A typical allele consists of a perfect palindrome, producing ~10-5 de novo t(11;22) translocations. Alleles with an asymmetric center do not form the t(11;22). Our data show the importance of genome sequence on chromosomal rearrangements, a class of human mutation that is thought to be random.