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Register a new userInferring Admixture Histories of Human Populations Using Linkage Disequilibrium
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Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.
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One of the outstanding challenges in comparative genomics is to interpret the evolutionary importance of regulatory variation between species. Rigorous molecular evolution-based methods to infer evidence for natural selection from expression data are at a premium in the field, and to date, phylogenetic approaches have not been well-suited to address the question in the small sets of taxa profiled in standard surveys of gene expression. We have developed a strategy to infer evolutionary histories from expression profiles by analyzing suites of genes of common function. In a manner conceptually similar to molecular evolution models in which the evolutionary rates of DNA sequence at multiple loci follow a gamma distribution, we modeled expression of the genes of an emph{a priori}-defined pathway with rates drawn from an inverse gamma distribution. We then developed a fitting strategy to infer the parameters of this distribution from expression measurements, and to identify gene groups whose expression patterns were consistent with evolutionary constraint or rapid evolution in particular species. Simulations confirmed the power and accuracy of our inference method. As an experimental testbed for our approach, we generated and analyzed transcriptional profiles of four emph{Saccharomyces} yeasts. The results revealed pathways with signatures of constrained and accelerated regulatory evolution in individual yeasts and across the phylogeny, highlighting the prevalence of pathway-level expression change during the divergence of yeast species. We anticipate that our pathway-based phylogenetic approach will be of broad utility in the search to understand the evolutionary relevance of regulatory change.
Mathematical and computational modeling approaches are increasingly used as quantitative tools in the analysis and forecasting of infectious disease epidemics. The growing need for realism in addressing complex public health questions is however calling for accurate models of the human contact patterns that govern the disease transmission processes. Here we present a data-driven approach to generate effective descriptions of population-level contact patterns by using highly detailed macro (census) and micro (survey) data on key socio-demographic features. We produce age-stratified contact matrices for 277 sub-national administrative regions of countries covering approximately 3.5 billion people and reflecting the high degree of cultural and societal diversity of the focus countries. We use the derived contact matrices to model the spread of airborne infectious diseases and show that sub-national heterogeneities in human mixing patterns have a marked impact on epidemic indicators such as the reproduction number and overall attack rate of epidemics of the same etiology. The contact patterns derived here are made publicly available as a modeling tool to study the impact of socio-economic differences and demographic heterogeneities across populations on the epidemiology of infectious diseases.
Admixed populations are formed by the merging of two or more ancestral populations, and the ancestry of each locus in an admixed genome derives from either source. Consider a simple pulse admixture model, where populations A and B merged t generations ago without subsequent gene flow. We derive the distribution of the proportion of an admixed chromosome that has A (or B) ancestry, as a function of the chromosome length L, t, and the initial contribution of the A source, m. We demonstrate that these results can be used for inference of the admixture parameters. For more complex admixture models, we derive an expression in Laplace space for the distribution of ancestry proportions that depends on having the distribution of the lengths of segments of each ancestry. We obtain explicit results for the special case of a two-wave admixture model, where population A contributed additional migrants in one of the generations between the present and the initial admixture event. Specifically, we derive formulas for the distribution of A and B segment lengths and numerical results for the distribution of ancestry proportions. We show that for recent admixture, data generated under a two-wave model can hardly be distinguished from that generated under a pulse model.
We sequenced genomes from a $sim$7,000 year old early farmer from Stuttgart in Germany, an $sim$8,000 year old hunter-gatherer from Luxembourg, and seven $sim$8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations deep relationships and show that EEF had $sim$44% ancestry from a Basal Eurasian lineage that split prior to the diversification of all other non-African lineages.
Identifying directed interactions between species from time series of their population densities has many uses in ecology. This key statistical task is equivalent to causal time series inference, which connects to the Granger causality (GC) concept: $x$ causes $y$ if $x$ improves the prediction of $y$ in a dynamic model. However, the entangled nature of nonlinear ecological systems has led to question the appropriateness of Granger causality, especially in its classical linear Multivariate AutoRegressive (MAR) model form. Convergent-cross mapping (CCM), a nonparametric method developed for deterministic dynamical systems, has been suggested as an alternative. Here, we show that linear GC and CCM are able to uncover interactions with surprisingly similar performance, for predator-prey cycles, 2-species deterministic (chaotic) or stochastic competition, as well as 10- and 20-species interaction networks. There is no correspondence between the degree of nonlinearity of the dynamics and which method performs best. Our results therefore imply that Granger causality, even in its linear MAR($p$) formulation, is a valid method for inferring interactions in nonlinear ecological networks; using GC or CCM (or both) can instead be decided based on the aims and specifics of the analysis.
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