Ancestral Population Structure Research Articles

On the genes, genealogies, and geographies of Quebec.

Population genetic models only provide coarse representations of real-world ancestry. We used a pedigree compiled from 4 million parish records and genotype data from 2276 French and 20,451 French Canadian individuals to finely model and trace French Canadian ancestry through space and time. The loss of ancestral French population structure and the appearance of spatial and regional structure highlights a wide range of population expansion models. Geographic features shaped migrations, and we find enrichments for migration, genetic, and genealogical relatedness patterns within river networks across regions of Quebec. Finally, we provide a freely accessible simulated whole-genome sequence dataset with spatiotemporal metadata for 1,426,749 individuals reflecting intricate French Canadian population structure. Such realistic population-scale simulations provide opportunities to investigate population genetics at an unprecedented resolution.

Range-wide whole-genome resequencing of the brown bear reveals drivers of intraspecies divergence

Population-genomic studies can shed new light on the effect of past demographic processes on contemporary population structure. We reassessed phylogeographical patterns of a classic model species of postglacial recolonisation, the brown bear (Ursus arctos), using a range-wide resequencing dataset of 128 nuclear genomes. In sharp contrast to the erratic geographical distribution of mtDNA and Y-chromosomal haplotypes, autosomal and X-chromosomal multi-locus datasets indicate that brown bear population structure is largely explained by recent population connectivity. Multispecies coalescent based analyses reveal cases where mtDNA haplotype sharing between distant populations, such as between Iberian and southern Scandinavian bears, likely results from incomplete lineage sorting, not from ancestral population structure (i.e., postglacial recolonisation). However, we also argue, using forward-in-time simulations, that gene flow and recombination can rapidly erase genomic evidence of former population structure (such as an ancestral population in Beringia), while this signal is retained by Y-chromosomal and mtDNA, albeit likely distorted. We further suggest that if gene flow is male-mediated, the information loss proceeds faster in autosomes than in X chromosomes. Our findings emphasise that contemporary autosomal genetic structure may reflect recent population dynamics rather than postglacial recolonisation routes, which could contribute to mtDNA and Y-chromosomal discordances.

Ghosts of a Structured Past: Impacts of Ancestral Patterns of Isolation-by-Distance on Divergence-Time Estimation.

Isolation-by-distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the population size. Next, we simulate whole genomes to obtain single nucleotide polymorphisms (SNPs), and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. Finally, we demonstrate the impact of ancestral isolation-by-distance on divergence-time estimation using an empirical dataset of squamates (Tropidurus) endemic to Brazil. We conclude that studies estimating divergence times should be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.

Ancestral European Origins and Population Structure of Helicobacter pylori Strains from an Iranian Population

Ancestral European Origins and Population Structure of Helicobacter pylori Strains from an Iranian Population

Maximum Likelihood Estimation of Species Trees from Gene Trees in the Presence of Ancestral Population Structure.

Though large multilocus genomic data sets have led to overall improvements in phylogenetic inference, they have posed the new challenge of addressing conflicting signals across the genome. In particular, ancestral population structure, which has been uncovered in a number of diverse species, can skew gene tree frequencies, thereby hindering the performance of species tree estimators. Here we develop a novel maximum likelihood method, termed TASTI (Taxa with Ancestral structure Species Tree Inference), that can infer phylogenies under such scenarios, and find that it has increasing accuracy with increasing numbers of input gene trees, contrasting with the relatively poor performances of methods not tailored for ancestral structure. Moreover, we propose a supertree approach that allows TASTI to scale computationally with increasing numbers of input taxa. We use genetic simulations to assess TASTI’s performance in the three- and four-taxon settings and demonstrate the application of TASTI on a six-species Afrotropical mosquito data set. Finally, we have implemented TASTI in an open-source software package for ease of use by the scientific community.

Hybridization preceded radiation in diploid wheats

Evolutionary relationships among the Aegilops-Triticum relatives of cultivated wheats have been difficult to resolve owing to incomplete lineage sorting and reticulate evolution. Recent studies have suggested that the wheat D-genome lineage (progenitor of Ae. tauschii) originated through homoploid hybridization between the A-genome lineage (progenitor of Triticum s.str.) and the B-genome lineage (progenitor of Ae. speltoides). This scenario of reticulation has been debated, calling for adequate phylogenetic analyses based on comprehensive sampling. To reconstruct the evolution of Aegilops-Triticum diploids, we here combined high-throughput sequencing of 38 nuclear low-copy loci of multiple accessions of all 13 species with inferences of the species phylogeny using the full-parameterized MCMC_SEQ method. Phylogenies recovered a monophyletic Aegilops-Triticum lineage that began diversifying ~6.6 Ma ago and gave rise to four sublineages, i.e. the A- (2 species), B- (1 species), D- (9 species) and T- (Ae. mutica) genome lineage. Full-parameterized phylogenies as well as patterns of tree dilation and tree compression supported a hybrid origin of the D-genome lineage from A and B ~3.0–4.0 Ma ago, and did not indicate additional hybridization events. Conflicting ABBA-BABA tests suggestive of further reticulation were shown here to result from ancestral population structure rather than hybridization. This comprehensive and dated phylogeny of wheat relatives indicates that the origin of the hybrid D-genome was followed by intense diversification into the majority of extant diploid as well as allopolyploid wild wheats.

The Effect of Gene Flow on Coalescent-based Species-Tree Inference.

Most current methods for inferring species-level phylogenies under the coalescent model assume that no gene flow occurs following speciation. Several studies have examined the impact of gene flow (e.g., Eckert and Carstens 2008; Chung and Ané 2011; Leaché et al. 2014; Solís-Lemus et al. 2016) and of ancestral population structure (DeGeorgio and Rosenberg 2016) on the performance of species-level phylogenetic inference, and analytic results have been proven for network models of gene flow (e.g., Solís-Lemus et al. 2016; Zhu et al. 2016). However, there are few analytic results for a continuous model of gene flow following speciation, despite the development of mathematical tools that could facilitate such study (e.g., Hobolth et al. 2011; Andersen et al. 2014; Tian and Kubatko 2016). In this article, we consider a three-taxon isolation-with-migration model that allows gene flow between sister taxa for a brief period following speciation, as well as variation in the effective population sizes across the species tree. We derive the probabilities of each of the three gene tree topologies under this model, and show that for certain choices of the gene flow and effective population size parameters, anomalous gene trees (i.e., gene trees that are discordant with the species tree but that have higher probability than the gene tree concordant with the species tree) exist. We characterize the region of parameter space producing anomalous trees and show that the probability of the gene tree that is concordant with the species tree can be arbitrarily small. We then show that there is theoretical support for using SVDQuartets with an outgroup to infer the rooted three-taxon species tree in a model of gene flow between sister taxa. We study the performance of SVDQuartets on simulated data and compare it to three other commonly-used methods for species tree inference, ASTRAL, MP-EST, and concatenation. The simulations show that ASTRAL, MP-EST, and concatenation can be statistically inconsistent when gene flow is present, while SVDQuartets performs well, though large sample sizes may be required for certain parameter choices.

Distinguishing recent admixture from ancestral population structure.

We develop and test two methods for distinguishing between recent admixture and ancestral population structure as explanations for greater similarity of one of two populations to an outgroup population. This problem arose when Neanderthals were found to be slightly more similar to nonAfrican than to African populations. The excess similarity is consistent with both recent admixture from Neanderthals into the ancestors of nonAfricans and subdivision in the ancestral population. Although later studies showed that there had been recent admixture, distinguishing between these two classes of models will be important in other situations, particularly when high-coverage genomes cannot be obtained for all populations. One of our two methods is based on the properties of the doubly conditioned frequency spectrum combined with the unconditional frequency spectrum. This method does not require a linkage map and can be used when there is relatively low coverage. The second method uses the extent of linkage disequilibrium among closely linked markers.

Consistency and inconsistency of consensus methods for inferring species trees from gene trees in the presence of ancestral population structure

In the last few years, several statistically consistent consensus methods for species tree inference have been devised that are robust to the gene tree discordance caused by incomplete lineage sorting in unstructured ancestral populations. One source of gene tree discordance that has only recently been identified as a potential obstacle for phylogenetic inference is ancestral population structure. In this article, we describe a general model of ancestral population structure, and by relying on a single carefully constructed example scenario, we show that the consensus methods Democratic Vote, STEAC, STAR, R∗ Consensus, Rooted Triple Consensus, Minimize Deep Coalescences, and Majority-Rule Consensus are statistically inconsistent under the model. We find that among the consensus methods evaluated, the only method that is statistically consistent in the presence of ancestral population structure is GLASS/Maximum Tree. We use simulations to evaluate the behavior of the various consensus methods in a model with ancestral population structure, showing that as the number of gene trees increases, estimates on the basis of GLASS/Maximum Tree approach the true species tree topology irrespective of the level of population structure, whereas estimates based on the remaining methods only approach the true species tree topology if the level of structure is low. However, through simulations using species trees both with and without ancestral population structure, we show that GLASS/Maximum Tree performs unusually poorly on gene trees inferred from alignments with little information. This practical limitation of GLASS/Maximum Tree together with the inconsistency of other methods prompts the need for both further testing of additional existing methods and development of novel methods under conditions that incorporate ancestral population structure.

Using Network Methodology to Infer Population Substructure

One of the main caveats of association studies is the possible affection by bias due to population stratification. Existing methods rely on model-based approaches like structure and ADMIXTURE or on principal component analysis like EIGENSTRAT. Here we provide a novel visualization technique and describe the problem of population substructure from a graph-theoretical point of view. We group the sequenced individuals into triads, which depict the relational structure, on the basis of a predefined pairwise similarity measure. We then merge the triads into a network and apply community detection algorithms in order to identify homogeneous subgroups or communities, which can further be incorporated as covariates into logistic regression. We apply our method to populations from different continents in the 1000 Genomes Project and evaluate the type 1 error based on the empirical p-values. The application to 1000 Genomes data suggests that the network approach provides a very fine resolution of the underlying ancestral population structure. Besides we show in simulations, that in the presence of discrete population structures, our developed approach maintains the type 1 error more precisely than existing approaches.

Multicolonial population structure and nestmate recognition in an extremely dense population of the European ant Lasius flavus

Under optimal ecological conditions ant populations can reach high nest densities, leading to strong competition between colonies and affecting ant behaviour and sociogenetic structure. Extremely high population densities are commonly found in invasive ant species in which all colonies of a population act as a single super-colony with no behavioural or genetic boundaries between nests. In contrast, the typical and ancestral ant population structure consists of discrete genetic units, i.e. colonies with a single or few queens and highly related workers. The subterranean mound building ant Lasius flavus, which is native to Central Europe, reaches nest densities of up to 0.5 colonies per m2 in our study population in Southern Germany. We investigated the sociogenetic structure and its temporal stability in this dense population using genomic microsatellites. Despite close proximity, neighbouring nests were generally genetically distinct. Most mounds were inhabited by a single colony, but we also found a few polydomous colonies spreading over two or more mounds. About half of all colonies were monogynous, the others either polygynous and/or polyandrous. We re-sampled mounds after 8 months and found mound occupancy to be predominantly stable over time. Behavioural experiments revealed low aggression between workers from different nests, albeit these ants recognised their nestmates. Our study demonstrates that native ant species can reach high densities despite a multi-colonial population structure and that intense competition does not invariably lead to high aggression between nests.

An evolutionary history of the selectin gene cluster in humans

Molecules involved in leukocyte trafficking have a central role in the development of inflammatory and immune responses. We performed F(ST) analysis of the selectin cluster, as well as of SELPLG, ICAM1 and VCAM1. Peaks of significantly high population genetic differentiation were restricted to two regions in SELP and one in SELPLG. Resequencing data indicated that the region covering SELP exons 11-13 displays high nucleotide diversity in Africans and Europeans (CEU), and a high level of within-species diversity compared with inter-specific divergence. Analysis of inferred haplotypes revealed a complex phylogeny with two deeply separated clades that coalesce at ~3.5 million years (MY) plus a minor clade with a TMRCA (time to the most recent common ancestor) of ~2.2 MY. A splicing assay indicated no haplotype-specific effect on SELP exon 14 inclusion. These data are consistent with a model of multiallelic balancing selection; single-nucleotide polymorphism analysis indicated that the Val640Leu variant represents a likely selection target. In populations of Asian ancestry a distinct haplotype, possibly carrying regulatory variants, has been driven to high frequency by positive selection. No deviation from neutrality was observed for the SELPLG region. Resequencing of SELP in chimpanzees revealed a haplotype phylogeny with extremely deep basal branches, suggesting either long-standing balancing selection or ancestral population structure. Thus, SELP has experienced a complex selective history, possibly as a result of local adaptation. Variants in the gene have been associated with autoimmune and cardiovascular diseases. Association studies would benefit from both taking the complex SELP haplotype structure into account and from analysis of possible regulatory variants in the gene.

The Pipid Root

The estimation of phylogenetic relationships is an essential component of understanding evolution. Accurate phylogenetic estimation is difficult, however, when internodes are short and old, when genealogical discordance is common due to large ancestral effective population sizes or ancestral population structure, and when homoplasy is prevalent. Inference of divergence times is also hampered by unknown and uneven rates of evolution, the incomplete fossil record, uncertainty in relationships between fossil and extant lineages, and uncertainty in the age of fossils. Ideally, these challenges can be overcome by developing large "phylogenomic" data sets and by analyzing them with methods that accommodate features of the evolutionary process, such as genealogical discordance, recurrent substitution, recombination, ancestral population structure, gene flow after speciation among sampled and unsampled taxa, and variation in evolutionary rates. In some phylogenetic problems, it is possible to use information that is independent of fossils, such as the geological record, to identify putative triggers for diversification whose associated estimated divergence times can then be compared a posteriori with estimated relationships and ages of fossils. The history of diversification of pipid frog genera Pipa, Hymenochirus, Silurana, and Xenopus, for instance, is characterized by many of these evolutionary and analytical challenges. These frogs diversified dozens of millions of years ago, they have a relatively rich fossil record, their distributions span continental plates with a well characterized geological record of ancient connectivity, and there is considerable disagreement across studies in estimated evolutionary relationships. We used high throughput sequencing and public databases to generate a large phylogenomic data set with which we estimated evolutionary relationships using multilocus coalescence methods. We collected sequence data from Pipa, Hymenochirus, Silurana, and Xenopus and the outgroup taxon Rhinophrynus dorsalis from coding sequence of 113 autosomal regions, averaging ∼300 bp in length (range: 102-1695 bp) and also a portion of the mitochondrial genome. Analysis of these data using multiple approaches recovers strong support for the ((Xenopus, Silurana)(Pipa, Hymenochirus)) topology, and geologically calibrated divergence time estimates that are consistent with estimated ages and phylogenetic affinities of many fossils. These results provide new insights into the biogeography and chronology of pipid diversification during the breakup of Gondwanaland and illustrate how phylogenomic data may be necessary to tackle tough problems in molecular systematics. [Coalescence; gene tree; high-throughout sequencing; lineage sorting; pipid; species tree; Xenopus.].

Population Genetics of IFIH1: Ancient Population Structure, Local Selection, and Implications for Susceptibility to Type 1 Diabetes

The human interferon induced with helicase C domain 1 (IFIH1) gene encodes a sensor of double-strand RNA involved in innate immunity against viruses, indicating that this gene is a likely target of virus-driven selective pressure. Notably, IFIH1 also plays a role in autoimmunity, as common and rare polymorphisms in this gene have been associated with type 1 diabetes (T1D). We analyzed the evolutionary history of IFIH1 in human populations. Results herein suggest that two major IFIH1 haplotype clades originated from ancestral population structure (or balancing selection) in the African continent and that local selective pressures have acted on the gene. Specifically, directional selection in Europe and Asia resulted in the spread of a common IFIH1 haplotype carrying a derived His460 allele. This variant changes a highly conserved arginine residue in the helicase domain, possibly conferring altered specificity in viral recognition. An alternative common haplotype has swept to high frequency in South Americans as a result of recent positive selection. Previous studies suggested that a portion of risk alleles for autoimmune diseases could have been maintained in humans as they conferred a selective advantage against infections. This is not the case for IFIH1, as population genetic differentiation and haplotype analyses indicated that the T1D susceptibility alleles behaved as neutral or nearly neutral polymorphisms. Our findings suggest that variants in IFIH1 confer different susceptibility to diverse viral infections and provide insight into the relationship between adaptation to past infection and predisposition to autoimmunity in modern populations.

The cryptic genetic structure of the North American captive gorilla population

Western lowland gorillas (Gorilla gorilla gorilla) were imported from across their geographical range to North American zoos from the late 1800s through 1974. The majority of these gorillas were imported with little or no information regarding their original provenance and no information on their genetic relatedness. Here, we analyze 32 microsatellite loci in 144 individuals using a Bayesian clustering method to delineate clusters of individuals among a sample of founders of the captive North American zoo gorilla collection. We infer that the majority of North American zoo founders sampled are distributed into two distinct clusters, and that some individuals are of admixed ancestry. This new information regarding the existence of ancestral genetic population structure in the North American zoo population lays the groundwork for enhanced efforts to conserve the evolutionary units of the western lowland gorilla gene pool. Our data also show that the genetic diversity estimates in the founder population were comparable to those in wild gorilla populations (Mondika and Cross River), and that pairwise relatedness among the founders is no different from that expected for a random mating population. However, the relatively high level of relatedness (R = 0.54) we discovered in a pair of known breeding pairs reveals the need for incorporating genetic relatedness estimates in the captive management of western lowland gorillas.

The Complex Evolutionary History of Gorillas: Insights from Genomic Data

Relatively little is known about the evolutionary and demographic histories of gorillas, one of our closest living relatives. In this study, we used samples from both western (Gorilla gorilla) and eastern (Gorilla beringei) gorillas to infer the timing of the split between these geographically disjunct populations and to elaborate the demographic history of gorillas. Here we present DNA sequences from 16 noncoding autosomal loci from 15 western gorillas and 3 eastern gorillas, including 2 noninvasively sampled free-ranging individuals. We find that the genetic diversity of gorillas is similar to that of chimpanzees but almost twice as high as that of bonobos and humans. A significantly positive Fu & Li's D was observed for western gorillas, suggesting a complex demographic history with a constant, long-term population size and ancestral population structure. Among different population-split scenarios, our data suggest a complex history of western and eastern gorillas including an initial population split at around 0.9-1.6 MYA and subsequent, primarily male-mediated gene flow until approximately 80,000-200,000 years ago. Furthermore, simulations revealed that more gene flow took place from eastern to western gorilla populations than vice versa.

The Heritage of Pathogen Pressures and Ancient Demography in the Human Innate-Immunity CD209/CD209L Region

The innate immunity system constitutes the first line of host defense against pathogens. Two closely related innate immunity genes, CD209 and CD209L, are particularly interesting because they directly recognize a plethora of pathogens, including bacteria, viruses, and parasites. Both genes, which result from an ancient duplication, possess a neck region, made up of seven repeats of 23 amino acids each, known to play a major role in the pathogen-binding properties of these proteins. To explore the extent to which pathogens have exerted selective pressures on these innate immunity genes, we resequenced them in a group of samples from sub-Saharan Africa, Europe, and East Asia. Moreover, variation in the number of repeats of the neck region was defined in the entire Human Genome Diversity Panel for both genes. Our results, which are based on diversity levels, neutrality tests, population genetic distances, and neck-region length variation, provide genetic evidence that CD209 has been under a strong selective constraint that prevents accumulation of any amino acid changes, whereas CD209L variability has most likely been shaped by the action of balancing selection in non-African populations. In addition, our data point to the neck region as the functional target of such selective pressures: CD209 presents a constant size in the neck region populationwide, whereas CD209L presents an excess of length variation, particularly in non-African populations. An additional interesting observation came from the coalescent-based CD209 gene tree, whose binary topology and time depth (approximately 2.8 million years ago) are compatible with an ancestral population structure in Africa. Altogether, our study has revealed that even a short segment of the human genome can uncover an extraordinarily complex evolutionary history, including different pathogen pressures on host genes as well as traces of admixture among archaic hominid populations.