Current methods for inferring population structure from genetic data do not provide formal significance tests for population differentiation. We discuss an approach to studying population structure ...(principal components analysis) that was first applied to genetic data by Cavalli-Sforza and colleagues. We place the method on a solid statistical footing, using results from modern statistics to develop formal significance tests. We also uncover a general "phase change" phenomenon about the ability to detect structure in genetic data, which emerges from the statistical theory we use, and has an important implication for the ability to discover structure in genetic data: for a fixed but large dataset size, divergence between two populations (as measured, for example, by a statistic like FST) below a threshold is essentially undetectable, but a little above threshold, detection will be easy. This means that we can predict the dataset size needed to detect structure.
Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to ...interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000-86,000 years before the present (BP), and most likely 47,000-65,000 years ago. This supports the recent interbreeding hypothesis and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.
Recent studies have shown that admixture has been pervasive throughout human history. While several methods exist for dating admixture in contemporary populations, they are not suitable for sparse, ...low coverage ancient genomic data. Thus, we developed
that leverages ancestry covariance patterns across the genome of a single individual to infer the timing of admixture.
provides reliable estimates under various demographic scenarios and outperforms available methods for ancient DNA applications. Using
on ~1,100 ancient genomes, we reconstruct major gene flow events during European Holocene. By studying the genetic formation of Anatolian farmers, we infer that gene flow related to Iranian Neolithic farmers occurred before 9,600 BCE, predating the advent of agriculture in Anatolia. Contrary to the archaeological evidence, we estimate that early Steppe pastoralist groups (Yamnaya and Afanasievo) were genetically formed more than a millennium before the start of steppe pastoralism. Using time transect samples across sixteen regions, we provide a fine-scale chronology of the Neolithization of Europe and the rapid spread of Steppe pastoralist ancestry across Europe. Our analyses provide new insights on the origins and spread of farming and Indo-European languages, highlighting the power of genomic dating methods to elucidate the legacy of human migrations.
Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that ...enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.
Thanks to the rapid development in mobile vehicles and wireless technologies, the Internet of Vehicles (IoV) has become an attractive application that can provide a large number of mobile services ...for drivers. Vehicles can be informed of the mobile position, direction, speed, and other real-time information of nearby vehicles to avoid traffic jams and accidents. However, the environments of IoV could be dangerous in the absence of security protections. Due to the openness and self-organization of IoV, there are enormous malicious attackers. To guarantee the safety of mobile services, we propose an effective decentralized authentication mechanism for IoV on the basis of the consensus algorithm of blockchain technology. The simulation under the veins framework is carried out to verify the feasibility of the scheme in reducing the selfish behavior and malicious attacks in IoV.
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.
The study of human evolution has been revolutionized by inferences from ancient DNA analyses. Key to these studies is the reliable estimation of the age of ancient specimens. High-resolution age ...estimates can often be obtained using radiocarbon dating, and, while precise and powerful, this method has some biases, making it of interest to directly use genetic data to infer a date for samples that have been sequenced. Here, we report a genetic method that uses the recombination clock. The idea is that an ancient genome has evolved less than the genomes of present-day individuals and thus has experienced fewer recombination events since the common ancestor. To implement this idea, we take advantage of the insight that all non-Africans have a common heritage of Neanderthal gene flow into their ancestors. Thus, we can estimate the date since Neanderthal admixture for present-day and ancient samples simultaneously and use the difference as a direct estimate of the ancient specimen’s age. We apply our method to date five Upper Paleolithic Eurasian genomes with radiocarbon dates between 12,000 and 45,000 y ago and show an excellent correlation of the genetic and 14C dates. By considering the slope of the correlation between the genetic dates, which are in units of generations, and the 14C dates, which are in units of years, we infer that the mean generation interval in humans over this period has been 26–30 y. Extensions of this methodology that use older shared events may be applicable for dating beyond the radiocarbon frontier.
Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by ...genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.
Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, ...including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.
We used 20 de novo genome assemblies to probe the speciation history and architecture of gene flow in rapidly radiating
butterflies. Our tests to distinguish incomplete lineage sorting from ...introgression indicate that gene flow has obscured several ancient phylogenetic relationships in this group over large swathes of the genome. Introgressed loci are underrepresented in low-recombination and gene-rich regions, consistent with the purging of foreign alleles more tightly linked to incompatibility loci. Here, we identify a hitherto unknown inversion that traps a color pattern switch locus. We infer that this inversion was transferred between lineages by introgression and is convergent with a similar rearrangement in another part of the genus. These multiple de novo genome sequences enable improved understanding of the importance of introgression and selective processes in adaptive radiation.
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