Natural selection acting on complex traits hampers the predictive accuracy of polygenic scores in ancient samples.

The prediction of phenotypes from ancient humans has gained interest due to its potential to investigate the evolution of complex traits. These predictions are commonly performed using polygenic scores computed with DNA information from ancient humans along with genome-wide association studies (GWAS) data from present-day humans. However, numerous evolutionary processes could impact the prediction of phenotypes from ancient humans based on polygenic scores.

The Promise of Inferring the Past Using the Ancestral Recombination Graph.

The ancestral recombination graph (ARG) is a structure that represents the history of coalescent and recombination events connecting a set of sequences (Hudson RR. In: Futuyma D, Antonovics J, editors. Gene genealogies and the coalescent process.

Leveraging shared ancestral variation to detect local introgression.

Introgression is a common evolutionary phenomenon that results in shared genetic material across non-sister taxa. Existing statistical methods such as Patterson's D statistic can detect introgression by measuring an excess of shared derived alleles between populations. The D statistic is effective to detect genome-wide patterns of introgression but can give spurious inferences of introgression when applied to local regions.

A likelihood-based framework for demographic inference from genealogical trees.

The demographic history of a population drives the pattern of genetic variation and is encoded in the gene-genealogical trees of the sampled alleles. However, existing methods to infer demographic history from genetic data tend to use relatively low-dimensional summaries of the genealogy, such as allele frequency spectra. As a step toward capturing more of the information encoded in the genome-wide sequence of genealogical trees, here we propose a novel framework called the genealogical likelihood (gLike), which derives the full likelihood of a genealogical tree under any hypothesized demographic history.

Demographic modeling of admixed Latin American populations from whole genomes.

Demographic models of Latin American populations often fail to fully capture their complex evolutionary history, which has been shaped by both recent admixture and deeper-in-time demographic events. To address this gap, we used high-coverage whole-genome data from Indigenous American ancestries in present-day Mexico and existing genomes from across Latin America to infer multiple demographic models that capture the impact of different timescales on genetic diversity. Our approach, which combines analyses of allele frequencies and ancestry tract length distributions, represents a significant improvement over current models in predicting patterns of genetic variation in admixed Latin American populations.

Sequential hybridization may have facilitated ecological transitions in the Southwestern pinyon pine syngameon.

Multispecies interbreeding networks, or syngameons, have been increasingly reported in natural systems. However, the formation, structure, and maintenance of syngameons have received little attention. Through gene flow, syngameons can increase genetic diversity, facilitate the colonization of new environments, and contribute to hybrid speciation.

Changes in demography and geographic distribution in the weeping pinyon pine () during the Pleistocene.

Climate changes, together with geographical barriers imposed by the Sierra Madre Oriental and the Chihuahuan Desert, have shaped the genetic diversity and spatial distribution of different species in northern Mexico. Gordon & Glend. tolerates extremely arid conditions.

Haplotype-based inference of the distribution of fitness effects.

Recent genome sequencing studies with large sample sizes in humans have discovered a vast quantity of low-frequency variants, providing an important source of information to analyze how selection is acting on human genetic variation. In order to estimate the strength of natural selection acting on low-frequency variants, we have developed a likelihood-based method that uses the lengths of pairwise identity-by-state between haplotypes carrying low-frequency variants. We show that in some nonequilibrium populations (such as those that have had recent population expansions) it is possible to distinguish between positive or negative selection acting on a set of variants.

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative.

Populations, Traits, and Their Spatial Structure in Humans.

The spatial distribution of genetic variants is jointly determined by geography, past demographic processes, natural selection, and its interplay with environmental variation. A fraction of these genetic variants are "causal alleles" that affect the manifestation of a complex trait. The effect exerted by these causal alleles on complex traits can be independent or dependent on the environment.

Genomic evidence for the Old divergence of Southern European wolf populations.

The grey wolf () is one of the most widely distributed mammals in which a variety of distinct populations have been described. However, given their currently fragmented distribution and recent history of human-induced population decline, little is known about the events that led to their differentiation. Based on the analysis of whole canid genomes, we examined the divergence times between Southern European wolf populations and their ancient demographic history.

A community-maintained standard library of population genetic models.

The explosion in population genomic data demands ever more complex modes of analysis, and increasingly, these analyses depend on sophisticated simulations. Recent advances in population genetic simulation have made it possible to simulate large and complex models, but specifying such models for a particular simulation engine remains a difficult and error-prone task. Computational genetics researchers currently re-implement simulation models independently, leading to inconsistency and duplication of effort.

F between archaic and present-day samples.

The increasing abundance of DNA sequences obtained from fossils calls for new population genetics theory that takes account of both the temporal and spatial separation of samples. Here, we exploit the relationship between Wright's F and average coalescence times to develop an analytic theory describing how F depends on both the distance and time separating pairs of sampled genomes. We apply this theory to several simple models of population history.

Appropriate homoplasy metrics in linked SSRs to predict an underestimation of demographic expansion times.

Background: Homoplasy affects demographic inference estimates. This effect has been recognized and corrective methods have been developed. However, no studies so far have defined what homoplasy metrics best describe the effects on demographic inference, or have attempted to estimate such metrics in real data.

variants in high altitude Tibetan wolves were selectively introgressed into highland dogs.

Background: Admixture can facilitate adaptation. For example, black wolves have obtained the variant causing black coat color through past hybridization with domestic dogs and have higher fitness than gray colored wolves. Another recent example of the transfer of adaptive variation between the two species has been suggested by the similarity between high altitude Tibetan mastiffs and wolves at the gene, a transcription factor induced in low oxygen environments.

PReFerSim: fast simulation of demography and selection under the Poisson Random Field model.

Unlabelled: The Poisson Random Field (PRF) model has become an important tool in population genetics to study weakly deleterious genetic variation under complicated demographic scenarios. Currently, there are no freely available software applications that allow simulation of genetic variation data under this model. Here we present PReFerSim, an ANSI C program that performs forward simulations under the PRF model.

Genomic Flatlining in the Endangered Island Fox.

Genetic studies of rare and endangered species often focus on defining and preserving genetically distinct populations, especially those having unique adaptations [1, 2]. Much less attention is directed at understanding the landscape of deleterious variation, an insidious consequence of geographic isolation and the inefficiency of natural selection to eliminate harmful variants in small populations [3-5]. With population sizes of many vertebrates decreasing and isolation increasing through habitat fragmentation and loss, understanding the extent and nature of deleterious variation in small populations is essential for predicting and enhancing population persistence.

Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs.

Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication.

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection.

Worldwide patterns of genomic variation and admixture in gray wolves.

The gray wolf (Canis lupus) is a widely distributed top predator and ancestor of the domestic dog. To address questions about wolf relationships to each other and dogs, we assembled and analyzed a data set of 34 canine genomes. The divergence between New and Old World wolves is the earliest branching event and is followed by the divergence of Old World wolves and dogs, confirming that the dog was domesticated in the Old World.

Height-reducing variants and selection for short stature in Sardinia.

We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.

Genome sequencing highlights the dynamic early history of dogs.

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously.

Genetic, morphological, geographical and ecological approaches reveal phylogenetic relationships in complex groups, an example of recently diverged pinyon pine species (Subsection Cembroides).

Elucidating phylogenetic relationships and species boundaries within complex taxonomic groups is challenging for intrinsic and extrinsic (i.e., technical) reasons.