RAD‐sequencing for estimating genomic relatedness matrix‐based heritability in the wild: A case study in roe deer

Estimating the evolutionary potential of quantitative traits and reliably predicting responses to selection in wild populations are important challenges in evolutionary biology. The genomic revolution has opened up opportunities for measuring relatedness among individuals with precision, enabling pedigree‐free estimation of trait heritabilities in wild populations. However, until now, most quantitative genetic studies based on a genomic relatedness matrix (GRM) have focused on long‐term monitored populations for which traditional pedigrees were also available, and have often had access to knowledge of genome sequence and variability. Here, we investigated the potential of RAD‐sequencing for estimating heritability in a free‐ranging roe deer (Capreolous capreolus) population for which no prior genomic resources were available. We propose a step‐by‐step analytical framework to optimize the quality and quantity of the genomic data and explore the impact of the single nucleotide polymorphism (SNP) calling and filtering processes on the GRM structure and GRM‐based heritability estimates. As expected, our results show that sequence coverage strongly affects the number of recovered loci, the genotyping error rate and the amount of missing data. Ultimately, this had little effect on heritability estimates and their standard errors, provided that the GRM was built from a minimum number of loci (above 7,000). Genomic relatedness matrix‐based heritability estimates thus appear robust to a moderate level of genotyping errors in the SNP data set. We also showed that quality filters, such as the removal of low‐frequency variants, affect the relatedness structure of the GRM, generating lower h² estimates. Our work illustrates the huge potential of RAD‐sequencing for estimating GRM‐based heritability in virtually any natural population.     

Assessments of 226Ra and 222Rn concentration in well and tap water from Sik,Malaysia, and consequent dose estimates

Abstract

The ingestion of ²²⁶Ra, inhalation, and ingestion of ²²²Rn in water is considered the primary health risk for lungs and stomach. This study presents the concentrations of ²²⁶Ra and ²²²Rn in well and tap water collected from Sik, Malaysia, using HPGe and RAD7 detectors. Maximum average concentrations of ²²⁶Ra and ²²²Rn were found 47.6?±?3.6 mBq/l and 9.3?±?1.4?Bq/l in well water, respectively, and minimum were found 17.1?±?3.6 mBq/l and 1.6?±?1.0?Bq/l in tap water, respectively. A positive correlation (R=.88) was found between ²²⁶Ra and ²²²Rn determined by HPGe and RAD7 detectors, respectively. Infants in the age group of 0–1 y appeared to be at risk with respect to the annual effective doses from ²²⁶Ra and ²²²Rn as compared to the other age groups. However, annual effective doses for all three age groups from intake of ²²⁶Ra and ²²²Rn in well and tap drinking water were found below the World Health Organization (WHO) recommended level of .1 mSv/y_.     

BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation

1. Download high-res image (141KB)
2. Download full-size image

     

The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers

1. Download high-res image (224KB)
2. Download full-size image

     

Virulence and pathogenicity of a Candida albicans mutant with reduced filamentation

Deletion of DNA polymerase eta (Rad30/Polη) in pathogenic yeast Candida albicans is known to reduce filamentation induced by serum, ultraviolet, and cisplatin. Because nonfilamentous C. albicans is widely accepted as avirulent form, here we explored the virulence and pathogenicity of a rad30Δ strain of C. albicans in cell‐based and animal systems. Flow cytometry of cocultured fungal and differentiated macrophage cells revealed that comparatively higher percentage of macrophages was associated with the wild‐type than rad30Δ cells. In contrast, higher number of Polη‐deficient C. albicans adhered per macrophage membrane. Imaging flow cytometry showed that the wild‐type C. albicans developed hyphae after phagocytosis that caused necrotic death of macrophages to evade their clearance. Conversely, phagosomes kill the fungal cells as estimated by increased metacaspase activity in wild‐type C. albicans. Despite the morphological differences, both wild‐type and rad30? C. albicans were virulent with a varying degree of pathogenicity in mice models. Notably, mice with Th1 immunity were comparatively less susceptible to systemic fungal infection than Th2 type. Thus, our study clearly suggests that the modes of interaction of morphologically different C. albicans strains with the host immune cells are diverged, and host genetic background and several other attributing factors of the fungus could additionally determine their virulence.     

Predicting the success of an invader: Niche shift versus niche conservatism

Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype–environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat‐shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental‐induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe.     

Alternative Lengthening of Telomeres through Two Distinct Break-Induced Replication Pathways

1. Download high-res image (146KB)
2. Download full-size image

     

Solvation Energy and Thermal Stability of Hydrophilization-Modified α-Chymotrypsin

As reported in the literature [Mozhaev et al. (1988), Eur. J. Biochem. 173, 147–154], when a series of modifiers, especially the cyclic anhydrides of pyromellitic and mellitic acids, are introduced into each lysine located in the -chymotrypsin (CT) surface, a substantial hydrophilization of the enzyme surface can occur and remarkable stabilization effects of modified enzymes can be obtained. In this paper, four models are applied to calculate the solvation energy of native and the modified CT based on their tertiary structures, which can be built by the CVFF force field. Analyzing the relationship between the solvation energy and the thermal stability in detail, we find that the results of three solvation energy models (Ooi model, WE-1 model, and WE-2 model) can be used to illustrate the relative stability among these enzymes qualitatively. The present study should be of practical value as well as of some theoretical interest.