A mutation rate model at the basepair resolution identifies the mutagenic effect of polymerase III transcription.

De novo mutations occur at substantially different rates depending on genomic location, sequence context and DNA strand. The success of methods to estimate selection intensity, infer demographic history and map rare disease genes, depends strongly on assumptions about the local mutation rate. Here we present Roulette, a genome-wide mutation rate model at basepair resolution that incorporates known determinants of local mutation rate.

Mutation rates and adaptive variation among the clinically dominant clusters of .

() is a multidrug-resistant pathogen increasingly responsible for severe pulmonary infections. Analysis of whole-genome sequences (WGS) of demonstrates dense genetic clustering of clinical isolates collected from disparate geographic locations. This has been interpreted as supporting patient-to-patient transmission, but epidemiological studies have contradicted this interpretation.

Demographic and Viral-Genetic Analyses of COVID-19 Severity in Bahrain Identify Local Risk Factors and a Protective Effect of Polymerase Mutations.

A multitude of demographic, health, and genetic factors are associated with the risk of developing severe COVID-19 following infection by the SARS-CoV-2. There is a need to perform studies across human societies and to investigate the full spectrum of genetic variation of the virus. Using data from 869 COVID-19 patients in Bahrain between March 2020 and March 2021, we analyzed paired viral sequencing and non-genetic host data to understand host and viral determinants of severe COVID-19.

Maintenance of Complex Trait Variation: Classic Theory and Modern Data.

Numerous studies have found evidence that GWAS loci experience negative selection, which increases in intensity with the effect size of identified variants. However, there is also accumulating evidence that this selection is not entirely mediated by the focal trait and contains a substantial pleiotropic component. Understanding how selective constraint shapes phenotypic variation requires advancing models capable of balancing these and other components of selection, as well as empirical analyses capable of inferring this balance and how it is generated by the underlying biology.

Population-specific causal disease effect sizes in functionally important regions impacted by selection.

Many diseases exhibit population-specific causal effect sizes with trans-ethnic genetic correlations significantly less than 1, limiting trans-ethnic polygenic risk prediction. We develop a new method, S-LDXR, for stratifying squared trans-ethnic genetic correlation across genomic annotations, and apply S-LDXR to genome-wide summary statistics for 31 diseases and complex traits in East Asians (average N = 90K) and Europeans (average N = 267K) with an average trans-ethnic genetic correlation of 0.85.

Polygenic adaptation of rosette growth in Arabidopsis thaliana.

The rate at which plants grow is a major functional trait in plant ecology. However, little is known about its evolution in natural populations. Here, we investigate evolutionary and environmental factors shaping variation in the growth rate of Arabidopsis thaliana.

Maintenance of Adaptive Dynamics and No Detectable Load in a Range-Edge Outcrossing Plant Population.

During range expansion, edge populations are expected to face increased genetic drift, which in turn can alter and potentially compromise adaptive dynamics, preventing the removal of deleterious mutations and slowing down adaptation. Here, we contrast populations of the European subspecies Arabidopsis lyrata ssp. petraea, which expanded its Northern range after the last glaciation.

De Novo Mutation Rate Estimation in Wolves of Known Pedigree.

Knowledge of mutation rates is crucial for calibrating population genetics models of demographic history in units of years. However, mutation rates remain challenging to estimate because of the need to identify extremely rare events. We estimated the nuclear mutation rate in wolves by identifying de novo mutations in a pedigree of seven wolves.

The Effects of Demography and Genetics on the Neutral Distribution of Quantitative Traits.

Neutral models for quantitative trait evolution are useful for identifying phenotypes under selection. These models often assume normally distributed phenotypes. This assumption may be violated when a trait is affected by relatively few variants or when the effects of those variants arise from skewed or heavy tailed distributions.

Temporal and spatial alterations in mutant swarm size of St. Louis encephalitis virus in mosquito hosts.

St. Louis encephalitis virus (SLEV; Flaviviridae; Flavivirus) is a member of the Japanese encephalitis serocomplex and a close relative of West Nile virus (WNV). Although SLEV remains endemic to the US, both levels of activity and geographical dispersal are relatively constrained when compared to the widespread distribution of WNV.