188 research outputs found
The Population Genetic Signature of Polygenic Local Adaptation
Adaptation in response to selection on polygenic phenotypes may occur via
subtle allele frequencies shifts at many loci. Current population genomic
techniques are not well posed to identify such signals. In the past decade,
detailed knowledge about the specific loci underlying polygenic traits has
begun to emerge from genome-wide association studies (GWAS). Here we combine
this knowledge from GWAS with robust population genetic modeling to identify
traits that may have been influenced by local adaptation. We exploit the fact
that GWAS provide an estimate of the additive effect size of many loci to
estimate the mean additive genetic value for a given phenotype across many
populations as simple weighted sums of allele frequencies. We first describe a
general model of neutral genetic value drift for an arbitrary number of
populations with an arbitrary relatedness structure. Based on this model we
develop methods for detecting unusually strong correlations between genetic
values and specific environmental variables, as well as a generalization of
comparisons to test for over-dispersion of genetic values among
populations. Finally we lay out a framework to identify the individual
populations or groups of populations that contribute to the signal of
overdispersion. These tests have considerably greater power than their single
locus equivalents due to the fact that they look for positive covariance
between like effect alleles, and also significantly outperform methods that do
not account for population structure. We apply our tests to the Human Genome
Diversity Panel (HGDP) dataset using GWAS data for height, skin pigmentation,
type 2 diabetes, body mass index, and two inflammatory bowel disease datasets.
This analysis uncovers a number of putative signals of local adaptation, and we
discuss the biological interpretation and caveats of these results.Comment: 42 pages including 8 figures and 3 tables; supplementary figures and
tables not included on this upload, but are mostly unchanged from v
Robust identification of local adaptation from allele frequencies
Comparing allele frequencies among populations that differ in environment has
long been a tool for detecting loci involved in local adaptation. However, such
analyses are complicated by an imperfect knowledge of population allele
frequencies and neutral correlations of allele frequencies among populations
due to shared population history and gene flow. Here we develop a set of
methods to robustly test for unusual allele frequency patterns, and
correlations between environmental variables and allele frequencies while
accounting for these complications based on a Bayesian model previously
implemented in the software Bayenv. Using this model, we calculate a set of
`standardized allele frequencies' that allows investigators to apply tests of
their choice to multiple populations, while accounting for sampling and
covariance due to population history. We illustrate this first by showing that
these standardized frequencies can be used to calculate powerful tests to
detect non-parametric correlations with environmental variables, which are also
less prone to spurious results due to outlier populations. We then demonstrate
how these standardized allele frequencies can be used to construct a test to
detect SNPs that deviate strongly from neutral population structure. This test
is conceptually related to FST but should be more powerful as we account for
population history. We also extend the model to next-generation sequencing of
population pools, which is a cost-efficient way to estimate population allele
frequencies, but it implies an additional level of sampling noise. The utility
of these methods is demonstrated in simulations and by re-analyzing human SNP
data from the HGDP populations. An implementation of our method will be
available from http://gcbias.org.Comment: 27 pages, 7 figure
A genomic map of the effects of linked selection in Drosophila
Natural selection at one site shapes patterns of genetic variation at linked
sites. Quantifying the effects of 'linked selection' on levels of genetic
diversity is key to making reliable inference about demography, building a null
model in scans for targets of adaptation, and learning about the dynamics of
natural selection. Here, we introduce the first method that jointly infers
parameters of distinct modes of linked selection, notably background selection
and selective sweeps, from genome-wide diversity data, functional annotations
and genetic maps. The central idea is to calculate the probability that a
neutral site is polymorphic given local annotations, substitution patterns, and
recombination rates. Information is then combined across sites and samples
using composite likelihood in order to estimate genome-wide parameters of
distinct modes of selection. In addition to parameter estimation, this approach
yields a map of the expected neutral diversity levels along the genome. To
illustrate the utility of our approach, we apply it to genome-wide resequencing
data from 125 lines in Drosophila melanogaster and reliably predict diversity
levels at the 1Mb scale. Our results corroborate estimates of a high fraction
of beneficial substitutions in proteins and untranslated regions (UTR). They
allow us to distinguish between the contribution of sweeps and other modes of
selection around amino acid substitutions and to uncover evidence for pervasive
sweeps in untranslated regions (UTRs). Our inference further suggests a
substantial effect of linked selection from non-classic sweeps. More generally,
we demonstrate that linked selection has had a larger effect in reducing
diversity levels and increasing their variance in D. melanogaster than
previously appreciated
Selection and hybridization shaped the rapid spread of African honey bee ancestry in the Americas
Recent biological invasions offer ‘natural’ laboratories to understand the genetics and ecology of adaptation, hybridization, and range limits. One of the most impressive and well-documented biological invasions of the 20th century began in 1957 when Apis mellifera scutellata honey bees swarmed out of managed experimental colonies in Brazil. This newly-imported subspecies, native to southern and eastern Africa, both hybridized with and out-competed previously-introduced European honey bee subspecies. Populations of scutellata-European hybrid honey bees rapidly expanded and spread across much of the Americas in less than 50 years. We use broad geographic sampling and whole genome sequencing of over 300 bees to map the distribution of scutellata ancestry where the northern and southern invasions have presently stalled, forming replicated hybrid zones with European bee populations in California and Argentina. California is much farther from Brazil, yet these hybrid zones occur at very similar latitudes, consistent with the invasion having reached a climate barrier. At these range limits, we observe genome-wide clines for scutellata ancestry, and parallel clines for wing length that span hundreds of kilometers, supporting a smooth transition from climates favoring scutellata-European hybrid bees to climates where they cannot survive winter. We find no large effect loci maintaining exceptionally steep ancestry transitions. Instead, we find most individual loci have concordant ancestry clines across South America, with a build-up of somewhat steeper clines in regions of the genome with low recombination rates, consistent with many loci of small effect contributing to climate-associated fitness trade-offs. Additionally, we find no substantial reductions in genetic diversity associated with rapid expansions nor complete dropout of scutellata ancestry at any individual loci on either continent, which suggests that the competitive fitness advantage of scutellata ancestry at lower latitudes has a polygenic basis and that scutellata-European hybrid bees maintained large population sizes during their invasion. To test for parallel selection across continents, we develop a null model that accounts for drift in ancestry frequencies during the rapid expansion. We identify several peaks within a larger genomic region where selection has pushed scutellata ancestry to high frequency hundreds of kilometers past the present cline centers in both North and South America and that may underlie high-fitness traits driving the invasion.EEA BalcarceFil: Calfee, Erin. University of California. Department of Evolution and Ecology. Center for Population Biology; Estados UnidosFil: Agra, Marcelo Nicolás. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Palacio, María Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Ramírez, Santiago. University of California. Department of Evolution and Ecology. Center for Population Biology; Estados UnidosFil: Coop, Graham. University of California. Department of Evolution and Ecology . Center for Population Biology; Estados Unido
Live Hot, Die Young: Transmission Distortion in Recombination Hotspots
There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect
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Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans
Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.</p
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Adaptations to Climate in Candidate Genes for Common Metabolic Disorders
Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.</p
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