How Population Growth Affects Linkage Disequilibrium

The “LD curve” relates the linkage disequilibrium (LD) between pairs of nucleotide sites to the distance that separates them along the chromosome. The shape of this curve reflects natural selection, admixture between populations, and the history of population size. This article derives new results about the last of these effects. When a population expands in size, the LD curve grows steeper, and this effect is especially pronounced following a bottleneck in population size. When a population shrinks, the LD curve rises but remains relatively flat. As LD converges toward a new equilibrium, its time path may not be monotonic. Following an episode of growth, for example, it declines to a low value before rising toward the new equilibrium. These changes happen at different rates for different LD statistics. They are especially slow for estimates of σd2, which therefore allow inferences about ancient population history. For the human population of Europe, these results suggest a history of population growth.     

Possible ancestral structure in human populations

Determining the evolutionary relationships between fossil hominid groups such as Neanderthals and modern humans has been a question of enduring interest in human evolutionary genetics. Here we present a new method for addressing whether archaic human groups contributed to the modern gene pool (called ancient admixture), using the patterns of variation in contemporary human populations. Our method improves on previous work by explicitly accounting for recent population history before performing the analyses. Using sequence data from the Environmental Genome Project, we find strong evidence for ancient admixture in both a European and a West African population (p ≈ 10⁻⁷), with contributions to the modern gene pool of at least 5%. While Neanderthals form an obvious archaic source population candidate in Europe, there is not yet a clear source population candidate in West Africa.     

Genetic structure of chimpanzee populations

Little is known about the history and population structure of our closest living relatives, the chimpanzees, in part because of an extremely poor fossil record. To address this, we report the largest genetic study of the chimpanzees to date, examining 310 microsatellites in 84 common chimpanzees and bonobos. We infer three common chimpanzee populations, which correspond to the previously defined labels of “western,” “central,” and “eastern,” and find little evidence of gene flow between them. There is tentative evidence for structure within western chimpanzees, but we do not detect distinct additional populations. The data also provide historical insights, demonstrating that the western chimpanzee population diverged first, and that the eastern and central populations are more closely related in time.     

Uncovering the Genetic History of the Present-Day Greenlandic Population

Because of past limitations in samples and genotyping technologies, important questions about the history of the present-day Greenlandic population remain unanswered. In an effort to answer these questions and in general investigate the genetic history of the Greenlandic population, we analyzed ∼200,000 SNPs from more than 10% of the adult Greenlandic population (n = 4,674). We found that recent gene flow from Europe has had a substantial impact on the population: more than 80% of the Greenlanders have some European ancestry (on average ∼25% of their genome). However, we also found that the amount of recent European gene flow varies across Greenland and is far smaller in the more historically isolated areas in the north and east and in the small villages in the south. Furthermore, we found that there is substantial population structure in the Inuit genetic component of the Greenlanders and that individuals from the east, west, and north can be distinguished from each other. Moreover, the genetic differences in the Inuit ancestry are consistent with a single colonization wave of the island from north to west to south to east. Although it has been speculated that there has been historical admixture between the Norse Vikings who lived in Greenland for a limited period ∼600–1,000 years ago and the Inuit, we found no evidence supporting this hypothesis. Similarly, we found no evidence supporting a previously hypothesized admixture event between the Inuit in East Greenland and the Dorset people, who lived in Greenland before the Inuit.     

A Spatial Framework for Understanding Population Structure and Admixture

Geographic patterns of genetic variation within modern populations, produced by complex histories of migration, can be difficult to infer and visually summarize. A general consequence of geographically limited dispersal is that samples from nearby locations tend to be more closely related than samples from distant locations, and so genetic covariance often recapitulates geographic proximity. We use genome-wide polymorphism data to build “geogenetic maps,” which, when applied to stationary populations, produces a map of the geographic positions of the populations, but with distances distorted to reflect historical rates of gene flow. In the underlying model, allele frequency covariance is a decreasing function of geogenetic distance, and nonlocal gene flow such as admixture can be identified as anomalously strong covariance over long distances. This admixture is explicitly co-estimated and depicted as arrows, from the source of admixture to the recipient, on the geogenetic map. We demonstrate the utility of this method on a circum-Tibetan sampling of the greenish warbler (Phylloscopus trochiloides), in which we find evidence for gene flow between the adjacent, terminal populations of the ring species. We also analyze a global sampling of human populations, for which we largely recover the geography of the sampling, with support for significant histories of admixture in many samples. This new tool for understanding and visualizing patterns of population structure is implemented in a Bayesian framework in the program SpaceMix.     

A genome-wide analysis of admixture in Uyghurs and a high-density admixture map for disease-gene discovery

Following up on our previous study, we conducted a genome-wide analysis of admixture for two Uyghur population samples (HGDP-UG and PanAsia-UG), collected from the northern and southern regions of Xinjiang in China, respectively. Both HGDP-UG and PanAsia-UG showed a substantial admixture of East-Asian (EAS) and European (EUR) ancestries, with an empirical estimation of ancestry contribution of 53:47 (EAS:EUR) and 48:52 for HGDP-UG and PanAsia-UG, respectively. The effective admixture time under a model with a single pulse of admixture was estimated as 110 generations and 129 generations, or admixture events occurred about 2200 and 2580 years ago for HGDP-UG and PanAsia-UG, respectively, assuming an average of 20 yr per generation. Despite Uyghurs' earlier history compared to other admixture populations, admixture mapping, holds promise for this population, because of its large size and its mixture of ancestry from different continents. We screened multiple databases and identified a genome-wide single-nucleotide polymorphism panel that can distinguish EAS and EUR ancestry of chromosomal segments in Uyghurs. The panel contains 8150 ancestry-informative markers (AIMs) showing large frequency differences between EAS and EUR populations (F_ST > 0.25, mean F_ST = 0.43) but small frequency differences (7999 AIMs validated) within both populations (F_ST < 0.05, mean F_ST < 0.01). We evaluated the effectiveness of this admixture map for localizing disease genes in two Uyghur populations. To our knowledge, our map constitutes the first practical resource for admixture mapping in Uyghurs, and it will enable studies of diseases showing differences in genetic risk between EUR and EAS populations.     

Estimating divergence times from DNA sequences

The patterns of genetic variation within and among individuals and populations can be used to make inferences about the evolutionary forces that generated those patterns. Numerous population genetic approaches have been developed in order to infer evolutionary history. Here, we present the “Two-Two (TT)” and the “Two-Two-outgroup (TTo)” methods; two closely related approaches for estimating divergence time based in coalescent theory. They rely on sequence data from two haploid genomes (or a single diploid individual) from each of two populations. Under a simple population-divergence model, we derive the probabilities of the possible sample configurations. These probabilities form a set of equations that can be solved to obtain estimates of the model parameters, including population split times, directly from the sequence data. This transparent and computationally efficient approach to infer population divergence time makes it possible to estimate time scaled in generations (assuming a mutation rate), and not as a compound parameter of genetic drift. Using simulations under a range of demographic scenarios, we show that the method is relatively robust to migration and that the TTo method can alleviate biases that can appear from drastic ancestral population size changes. We illustrate the utility of the approaches with some examples, including estimating split times for pairs of human populations as well as providing further evidence for the complex relationship among Neandertals and Denisovans and their ancestors.     

A European Concern? Genetic Structure and Expansion of Golden Jackals (Canis aureus) in Europe and the Caucasus

In the first continent-wide study of the golden jackal (Canis aureus), we characterised its population genetic structure and attempted to identify the origin of European populations. This provided a unique insight into genetic characteristics of a native carnivore population with rapid large-scale expansion. We analysed 15 microsatellite markers and a 406 base-pair fragment of the mitochondrial control region. Bayesian-based and principal components methods were applied to evaluate whether the geographical grouping of samples corresponded with genetic groups. Our analysis revealed low levels of genetic diversity, reflecting the unique history of the golden jackal among Europe’s native carnivores. The results suggest ongoing gene flow between south-eastern Europe and the Caucasus, with both contributing to the Baltic population, which appeared only recently. The population from the Peloponnese Peninsula in southern Greece forms a common genetic cluster with samples from south-eastern Europe (ΔK approach in STRUCTURE, Principal Components Analysis [PCA]), although the results based on BAPS and the estimated likelihood in STRUCTURE indicate that Peloponnesian jackals may represent a distinct population. Moreover, analyses of population structure also suggest either genetic distinctiveness of the island population from Samos near the coast of Asia Minor (BAPS, most STRUCTURE, PCA), or possibly its connection with the Caucasus population (one analysis in STRUCTURE). We speculate from our results that ancient Mediterranean jackal populations have persisted to the present day, and have merged with jackals colonising from Asia. These data also suggest that new populations of the golden jackal may be founded by long-distance dispersal, and thus should not be treated as an invasive alien species, i.e. an organism that is “non-native to an ecosystem, and which may cause economic or environmental harm or adversely affect human health”. These insights into the genetic structure and ancestry of Baltic jackals have important implications for management and conservation of jackals in Europe. The golden jackal is listed as an Annex V species in the EU Habitats Directive and as such, considering also the results presented here, should be legally protected in all EU member states.     

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 detect nonparametric correlations with environmental variables; these correlations 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 F_ST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools—a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org.     

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Founder events play a critical role in shaping genetic diversity, fitness and disease risk in a population. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods require large sample sizes or phased genomes. Thus, we developed ASCEND that measures the correlation in allele sharing between pairs of individuals across the genome to infer the age and strength of founder events. We show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios. We then apply ASCEND to two species with contrasting evolutionary histories: ~460 worldwide human populations and ~40 modern dog breeds. In humans, we find that over half of the analyzed populations have evidence for recent founder events, associated with geographic isolation, modes of sustenance, or cultural practices such as endogamy. Notably, island populations have lower population sizes than continental groups and most hunter-gatherer, nomadic and indigenous groups have evidence of recent founder events. Many present-day groups––including Native Americans, Oceanians and South Asians––have experienced more extreme founder events than Ashkenazi Jews who have high rates of recessive diseases due their known history of founder events. Using ancient genomes, we show that the strength of founder events differs markedly across geographic regions and time––with three major founder events related to the peopling of Americas and a trend in decreasing strength of founder events in Europe following the Neolithic transition and steppe migrations. In dogs, we estimate extreme founder events in most breeds that occurred in the last 25 generations, concordant with the establishment of many dog breeds during the Victorian times. Our analysis highlights a widespread history of founder events in humans and dogs and elucidates some of the demographic and cultural practices related to these events.     

Reconstructing the History of Mesoamerican Populations through the Study of the Mitochondrial DNA Control Region

The study of genetic information can reveal a reconstruction of human population’s history. We sequenced the entire mtDNA control region (positions 16.024 to 576 following Cambridge Reference Sequence, CRS) of 605 individuals from seven Mesoamerican indigenous groups and one Aridoamerican from the Greater Southwest previously defined, all of them in present Mexico. Samples were collected directly from the indigenous populations, the application of an individual survey made it possible to remove related or with other origins samples. Diversity indices and demographic estimates were calculated. Also AMOVAs were calculated according to different criteria. An MDS plot, based on FST distances, was also built. We carried out the construction of individual networks for the four Amerindian haplogroups detected. Finally, barrier software was applied to detect genetic boundaries among populations. The results suggest: a common origin of the indigenous groups; a small degree of European admixture; and inter-ethnic gene flow. The process of Mesoamerica’s human settlement took place quickly influenced by the region’s orography, which development of genetic and cultural differences facilitated. We find the existence of genetic structure is related to the region’s geography, rather than to cultural parameters, such as language. The human population gradually became fragmented, though they remained relatively isolated, and differentiated due to small population sizes and different survival strategies. Genetic differences were detected between Aridoamerica and Mesoamerica, which can be subdivided into “East”, “Center”, “West” and “Southeast”. The fragmentation process occurred mainly during the Mesoamerican Pre-Classic period, with the Otomí being one of the oldest groups. With an increased number of populations studied adding previously published data, there is no change in the conclusions, although significant genetic heterogeneity can be detected in Pima and Huichol groups. This result may be explained because populations historically assigned as belonging to the same group were, in fact, different indigenous populations.     

Bayesian identification of admixture events using multilocus molecular markers

Bayesian statistical methods for the estimation of hidden genetic structure of populations have gained considerable popularity in the recent years. Utilizing molecular marker data, Bayesian mixture models attempt to identify a hidden population structure by clustering individuals into genetically divergent groups, whereas admixture models target at separating the ancestral sources of the alleles observed in different individuals. We discuss the difficulties involved in the simultaneous estimation of the number of ancestral populations and the levels of admixture in studied individuals' genomes. To resolve this issue, we introduce a computationally efficient method for the identification of admixture events in the population history. Our approach is illustrated by analyses of several challenging real and simulated data sets. The software (baps), implementing the methods introduced here, is freely available at http://www.rni.helsinki.fi/~jic/bapspage.html.     

Demographic Inference Reveals African and European Admixture in the North American Drosophila melanogaster Population

Drosophila melanogaster spread from sub-Saharan Africa to the rest of the world colonizing new environments. Here, we modeled the joint demography of African (Zimbabwe), European (The Netherlands), and North American (North Carolina) populations using an approximate Bayesian computation (ABC) approach. By testing different models (including scenarios with continuous migration), we found that admixture between Africa and Europe most likely generated the North American population, with an estimated proportion of African ancestry of 15%. We also revisited the demography of the ancestral population (Africa) and found—in contrast to previous work—that a bottleneck fits the history of the population of Zimbabwe better than expansion. Finally, we compared the site-frequency spectrum of the ancestral population to analytical predictions under the estimated bottleneck model.     

Exploratory analysis of multi‐trait coadaptations in light of population history

During the process of range expansion, populations encounter a variety of environments. They respond to the local environments by modifying their mutually interacting traits. Common approaches of landscape analysis include first focusing on the genes that undergo diversifying selection or directional selection in response to environmental variation. To understand the whole history of populations, it is ideal to capture the history of their range expansion with reference to the series of surrounding environments and to infer the multitrait coadaptation. To this end, we propose a complementary approach; it is an exploratory analysis using up‐to‐date methods that integrate population genetic features and features of selection on multiple traits. First, we conduct correspondence analysis of site frequency spectra, traits, and environments with auxiliary information of population‐specific fixation index (F _ST). This visualizes the structure and the ages of populations and helps infer the history of range expansion, encountered environmental changes, and selection on multiple traits. Next, we further investigate the inferred history using an admixture graph that describes the population split and admixture. Finally, principal component analysis of the selection on edge‐by‐trait (SET) matrix identifies multitrait coadaptation and the associated edges of the admixture graph. We introduce a newly defined factor loadings of environmental variables in order to identify the environmental factors that caused the coadaptation. A numerical simulation of one‐dimensional stepping‐stone population expansion showed that the exploratory analysis reconstructed the pattern of the environmental selection that was missed by analysis of individual traits. Analysis of a public dataset of natural populations of black cottonwood in northwestern America identified the first principal component (PC) coadaptation of photosynthesis‐ vs growth‐related traits responding to the geographical clines of temperature and day length. The second PC coadaptation of volume‐related traits suggested that soil condition was a limiting factor for aboveground environmental selection.     

Region‐wide and ecotype‐specific differences in demographic histories of threespine stickleback populations,estimated from whole genome sequences

We analysed 81 whole genome sequences of threespine sticklebacks from Pacific North America, Greenland and Northern Europe, representing 16 populations. Principal component analysis of nuclear SNPs grouped populations according to geographical location, with Pacific populations being more divergent from each other relative to European and Greenlandic populations. Analysis of mitogenome sequences showed Northern European populations to represent a single phylogeographical lineage, whereas Greenlandic and particularly Pacific populations showed admixture between lineages. We estimated demographic history using a genomewide coalescence with recombination approach. The Pacific populations showed gradual population expansion starting >100 Kya, possibly reflecting persistence in cryptic refuges near the present distributional range, although we do not rule out possible influence of ancient admixture. Sharp population declines ca. 14–15 Kya were suggested to reflect founding of freshwater populations by marine ancestors. In Greenland and Northern Europe, demographic expansion started ca. 20–25 Kya coinciding with the end of the Last Glacial Maximum. In both regions, marine and freshwater populations started to show different demographic trajectories ca. 8–9 Kya, suggesting that this was the time of recolonization. In Northern Europe, this estimate was surprisingly late, but found support in subfossil evidence for presence of several freshwater fish species but not sticklebacks 12 Kya. The results demonstrate distinctly different demographic histories across geographical regions with potential consequences for adaptive processes. They also provide empirical support for previous assumptions about freshwater populations being founded independently from large, coherent marine populations, a key element in the Transporter Hypothesis invoked to explain the widespread occurrence of parallel evolution across freshwater stickleback populations.     

The timing of human adaptation from Neanderthal introgression

Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long-term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of adaptive Neanderthal introgression. From these, we identify cases in which Neanderthal-introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation and contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples.     

Reconstructing Roma History from Genome-Wide Data

The Roma people, living throughout Europe and West Asia, are a diverse population linked by the Romani language and culture. Previous linguistic and genetic studies have suggested that the Roma migrated into Europe from South Asia about 1,000–1,500 years ago. Genetic inferences about Roma history have mostly focused on the Y chromosome and mitochondrial DNA. To explore what additional information can be learned from genome-wide data, we analyzed data from six Roma groups that we genotyped at hundreds of thousands of single nucleotide polymorphisms (SNPs). We estimate that the Roma harbor about 80% West Eurasian ancestry–derived from a combination of European and South Asian sources–and that the date of admixture of South Asian and European ancestry was about 850 years before present. We provide evidence for Eastern Europe being a major source of European ancestry, and North-west India being a major source of the South Asian ancestry in the Roma. By computing allele sharing as a measure of linkage disequilibrium, we estimate that the migration of Roma out of the Indian subcontinent was accompanied by a severe founder event, which appears to have been followed by a major demographic expansion after the arrival in Europe.     

Between the Baltic and Danubian Worlds: The Genetic Affinities of a Middle Neolithic Population from Central Poland

For a long time, anthropological and genetic research on the Neolithic revolution in Europe was mainly concentrated on the mechanism of agricultural dispersal over different parts of the continent. Recently, attention has shifted towards population processes that occurred after the arrival of the first farmers, transforming the genetically very distinctive early Neolithic Linear Pottery Culture (LBK) and Mesolithic forager populations into present-day Central Europeans. The latest studies indicate that significant changes in this respect took place within the post-Linear Pottery cultures of the Early and Middle Neolithic which were a bridge between the allochthonous LBK and the first indigenous Neolithic culture of north-central Europe—the Funnel Beaker culture (TRB). The paper presents data on mtDNA haplotypes of a Middle Neolithic population dated to 4700/4600–4100/4000 BC belonging to the Brześć Kujawski Group of the Lengyel culture (BKG) from the Kuyavia region in north-central Poland. BKG communities constituted the border of the “Danubian World” in this part of Europe for approx. seven centuries, neighboring foragers of the North European Plain and the southern Baltic basin. MtDNA haplogroups were determined in 11 individuals, and four mtDNA macrohaplogroups were found (H, U5, T, and HV0). The overall haplogroup pattern did not deviate from other post-Linear Pottery populations from central Europe, although a complete lack of N1a and the presence of U5a are noteworthy. Of greatest importance is the observed link between the BKG and the TRB horizon, confirmed by an independent analysis of the craniometric variation of Mesolithic and Neolithic populations inhabiting central Europe. Estimated phylogenetic pattern suggests significant contribution of the post-Linear BKG communities to the origin of the subsequent Middle Neolithic cultures, such as the TRB.     

Modern human origins and prehistoric demography of Europe in light of the present-day genetic diversity

Dynamic advance in DNA sequencing methods and progress in formal population genetics analyses made it possible to infer aspects of human evolution from the DNA diversity distribution and frequency in contemporary populations. While providing some general background concerning the origins of modern human, this paper focuses on the dynamics of prehistoric population in Europe. The relevance of the present-day genetic diversity studies in elucidating prehistoric events is presented in the context of archeological and paleoanthropological evidence. The questions of the Neanderthal admixture as well as of the relative contribution of different waves of prehistoric migrations to the gene pool of modern Europeans are discussed.