The selection landscape and genetic legacy of ancient Eurasians.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years.

The evolutionary dynamics of local adaptations under genetic rescue is determined by mutational load and polygenicity.

Inbred populations often suffer from increased mutational load and reduced fitness due to lower efficacy of purifying selection in groups with small effective population sizes. Genetic rescue (GR) is a conservation tool that is studied and deployed with the aim of increasing the fitness of such inbred populations by assisted migration of individuals from closely related outbred populations. The success of GR depends on several factors-such as their demographic history and distribution of dominance effects of mutations-that may vary across populations.

Repeated origins, widespread gene flow, and allelic interactions of target-site herbicide resistance mutations.

Causal mutations and their frequency in agricultural fields are well-characterized for herbicide resistance. However, we still lack understanding of their evolutionary history: the extent of parallelism in the origins of target-site resistance (TSR), how long these mutations persist, how quickly they spread, and allelic interactions that mediate their selective advantage. We addressed these questions with genomic data from 19 agricultural populations of common waterhemp (), which we show to have undergone a massive expansion over the past century, with a contemporary effective population size estimate of 8 x 10.

Detecting Selection in Multiple Populations by Modeling Ancestral Admixture Components.

One of the most powerful and commonly used approaches for detecting local adaptation in the genome is the identification of extreme allele frequency differences between populations. In this article, we present a new maximum likelihood method for finding regions under positive selection. It is based on a Gaussian approximation to allele frequency changes and it incorporates admixture between populations.

Disentangling selection on genetically correlated polygenic traits via whole-genome genealogies.

We present a full-likelihood method to infer polygenic adaptation from DNA sequence variation and GWAS summary statistics to quantify recent transient directional selection acting on a complex trait. Through simulations of polygenic trait architecture evolution and GWASs, we show the method substantially improves power over current methods. We examine the robustness of the method under stratification, uncertainty and bias in marginal effects, uncertainty in the causal SNPs, allelic heterogeneity, negative selection, and low GWAS sample size.

An approximate full-likelihood method for inferring selection and allele frequency trajectories from DNA sequence data.

Most current methods for detecting natural selection from DNA sequence data are limited in that they are either based on summary statistics or a composite likelihood, and as a consequence, do not make full use of the information available in DNA sequence data. We here present a new importance sampling approach for approximating the full likelihood function for the selection coefficient. Our method CLUES treats the ancestral recombination graph (ARG) as a latent variable that is integrated out using previously published Markov Chain Monte Carlo (MCMC) methods.

Human Disease Variation in the Light of Population Genomics.

Identifying the causes of similarities and differences in genetic disease prevalence among humans is central to understanding disease etiology. While present-day humans are not strongly differentiated, vast amounts of genomic data now make it possible to study subtle patterns of genetic variation. This allows us to trace our genomic history thousands of years into the past and its implications for the distribution of disease-associated variants today.

Physiological and Genetic Adaptations to Diving in Sea Nomads.

Understanding the physiology and genetics of human hypoxia tolerance has important medical implications, but this phenomenon has thus far only been investigated in high-altitude human populations. Another system, yet to be explored, is humans who engage in breath-hold diving. The indigenous Bajau people ("Sea Nomads") of Southeast Asia live a subsistence lifestyle based on breath-hold diving and are renowned for their extraordinary breath-holding abilities.

Diversity of Translation Initiation Mechanisms across Bacterial Species Is Driven by Environmental Conditions and Growth Demands.

The Shine-Dalgarno (SD) sequence motif is frequently found upstream of protein coding genes and is thought to be the dominant mechanism of translation initiation used by bacteria. Experimental studies have shown that the SD sequence facilitates start codon recognition and enhances translation initiation by directly interacting with the highly conserved anti-SD sequence on the 30S ribosomal subunit. However, the proportion of SD-led genes within a genome varies across species and the factors governing this variation in translation initiation mechanisms remain largely unknown.