Inferring Population History Research Articles

Improved inference of population histories by integrating genomic and epigenomic data

Improved inference of population histories by integrating genomic and epigenomic data

Improved inference of population histories by integrating genomic and epigenomic data.

With the availability of high-quality full genome polymorphism (SNPs) data, it becomes feasible to study the past demographic and selective history of populations in exquisite detail. However, such inferences still suffer from a lack of statistical resolution for recent, for example bottlenecks, events, and/or for populations with small nucleotide diversity. Additional heritable (epi)genetic markers, such as indels, transposable elements, microsatellites, or cytosine methylation, may provide further, yet untapped, information on the recent past population history. We extend the Sequential Markovian Coalescent (SMC) framework to jointly use SNPs and other hyper-mutable markers. We are able to (1) improve the accuracy of demographic inference in recent times, (2) uncover past demographic events hidden to SNP-based inference methods, and (3) infer the hyper-mutable marker mutation rates under a finite site model. As a proof of principle, we focus on demographic inference in Arabidopsis thaliana using DNA methylation diversity data from 10 European natural accessions. We demonstrate that segregating single methylated polymorphisms (SMPs) satisfy the modeling assumptions of the SMC framework, while differentially methylated regions (DMRs) are not suitable as their length exceeds that of the genomic distance between two recombination events. Combining SNPs and SMPs while accounting for site- and region-level epimutation processes, we provide new estimates of the glacial age bottleneck and post-glacial population expansion of the European A. thaliana population. Our SMC framework readily accounts for a wide range of heritable genomic markers, thus paving the way for next-generation inference of evolutionary history by combining information from several genetic and epigenetic markers.

Biases in ARG-Based Inference of Historical Population Size in Populations Experiencing Selection.

Inferring the demographic history of populations provides fundamental insights into species dynamics and is essential for developing a null model to accurately study selective processes. However, background selection and selective sweeps can produce genomic signatures at linked sites that mimic or mask signals associated with historical population size change. While the theoretical biases introduced by the linked effects of selection have been well established, it is unclear whether ancestral recombination graph (ARG)-based approaches to demographic inference in typical empirical analyses are susceptible to misinference due to these effects. To address this, we developed highly realistic forward simulations of human and Drosophila melanogaster populations, including empirically estimated variability of gene density, mutation rates, recombination rates, purifying, and positive selection, across different historical demographic scenarios, to broadly assess the impact of selection on demographic inference using a genealogy-based approach. Our results indicate that the linked effects of selection minimally impact demographic inference for human populations, although it could cause misinference in populations with similar genome architecture and population parameters experiencing more frequent recurrent sweeps. We found that accurate demographic inference of D. melanogaster populations by ARG-based methods is compromised by the presence of pervasive background selection alone, leading to spurious inferences of recent population expansion, which may be further worsened by recurrent sweeps, depending on the proportion and strength of beneficial mutations. Caution and additional testing with species-specific simulations are needed when inferring population history with non-human populations using ARG-based approaches to avoid misinference due to the linked effects of selection.

Hybrids as mirrors of the past: genomic footprints reveal spatio-temporal dynamics and extinction risk of alpine extremophytes in the mountains of Central Asia.

Hybridization is one of the key processes shaping lineage diversification, particularly in regions that experienced strong climate oscillations. The alpine biome with its rich history of glacial-interglacial cycles and complex patterns of species distribution shifts offers an excellent system to investigate the impact of gene flow on population dynamics and speciation, important issues for evolutionary biology and biodiversity conservation. In this study, we combined genomic data (DArTseq), chloroplast markers, and morphology to examine phylogenetic relationships and the permeability of species boundaries and their evolutionary outcomes among the alpine extremophilic species of Puccinellia (Poaceae) in the Pamir Mountains, a part of the Mountains of Central Asia biodiversity hotspot. We determined the occurrence of interspecific hybrids between P. himalaica and P. pamirica, which demonstrated almost symmetric ancestry from their parental species and did not show signals of introgression. According to our integrative revision, the natural hybrids between P. himalaica and P. pamirica should be classified as Puccinellia ×vachanica (pro species). Using approximate Bayesian computation for population history inference, we uncovered that P. himalaica hybridized with P. pamirica independently in multiple localities over the Holocene. Hybrids inherited the fine-scale genetic structure from their parental species, which developed these patterns earlier, during the Late Pleistocene. Hybridization had different consequences for the involved parental lineages, likely playing an important role in a continuing decline of P. himalaica in the Pamir Mountains over the Holocene. Our results show that P. himalaica should be considered a critically endangered species in the Pamir Mountains and could also be retreating across its entire range of distribution in High Mountain Asia. Using a comparative phylogeographic framework, we revealed the risk of extinction of a cold-adapted alpine species in a global biodiversity hotspot. This study highlights that genomics could unravel diversity trends under climate change and provides valuable evidence for conservation management.

Worldwide Late Pleistocene and Early Holocene population declines in extant megafauna are associated with Homo sapiens expansion rather than climate change

The worldwide extinction of megafauna during the Late Pleistocene and Early Holocene is evident from the fossil record, with dominant theories suggesting a climate, human or combined impact cause. Consequently, two disparate scenarios are possible for the surviving megafauna during this time period - they could have declined due to similar pressures, or increased in population size due to reductions in competition or other biotic pressures. We therefore infer population histories of 139 extant megafauna species using genomic data which reveal population declines in 91% of species throughout the Quaternary period, with larger species experiencing the strongest decreases. Declines become ubiquitous 32–76 kya across all landmasses, a pattern better explained by worldwide Homo sapiens expansion than by changes in climate. We estimate that, in consequence, total megafauna abundance, biomass, and energy turnover decreased by 92–95% over the past 50,000 years, implying major human-driven ecosystem restructuring at a global scale.

Beta-PSMC: uncovering more detailed population history using beta distribution

BackgroundInferring the demographic history of a population is essential in population genetic studies. Though the inference methods based on the sequentially Markov coalescent can present the population history in detail, these methods assume that the population size remains unchanged in each time interval during discretizing the hidden state in the hidden Markov model. Therefore, these methods fail to uncover the detailed population history in each time interval.ResultsWe present a new method called Beta-PSMC, which introduces the probability density function of a beta distribution with a broad variety of shapes into the Pairwise Sequentially Markovian Coalescent (PSMC) model to refine the population history in each discretized time interval in place of the assumption that the population size is unchanged. Using simulation, we demonstrate that Beta-PSMC can uncover more detailed population history, and improve the accuracy and resolution of the recent population history inference. We also apply Beta-PSMC to infer the population history of Adélie penguin and find that the fluctuation in population size is contrary to the temperature change 15–27 thousand years ago.ConclusionsBeta-PSMC extends PSMC by allowing more detailed fluctuation of population size in each discretized time interval with the probability density function of beta distribution and will serve as a useful tool for population genetics.

Sex-biased admixture and assortative mating shape genetic variation and influence demographic inference in admixed Cabo Verdeans.

Genetic data can provide insights into population history, but first, we must understand the patterns that complex histories leave in genomes. Here, we consider the admixed human population of Cabo Verde to understand the patterns of genetic variation left by social and demographic processes. First settled in the late 1400s, Cabo Verdeans are admixed descendants of Portuguese colonizers and enslaved West African people. We consider Cabo Verde’s well-studied historical record alongside genome-wide SNP data from 563 individuals from 4 regions within the archipelago. We use genetic ancestry to test for patterns of nonrandom mating and sex-specific gene flow, and we examine the consequences of these processes for common demographic inference methods and genetic patterns. Notably, multiple population genetic tools that assume random mating underestimate the timing of admixture, but incorporating nonrandom mating produces estimates more consistent with historical records. We consider how admixture interrupts common summaries of genomic variation such as runs of homozygosity. While summaries of runs of homozygosity may be difficult to interpret in admixed populations, differentiating runs of homozygosity by length class shows that runs of homozygosity reflect historical differences between the islands in their contributions from the source populations and postadmixture population dynamics. Finally, we find higher African ancestry on the X chromosome than on the autosomes, consistent with an excess of European males and African females contributing to the gene pool. Considering these genomic insights into population history in the context of Cabo Verde’s historical record, we can identify how assumptions in genetic models impact inference of population history more broadly.

Tracing the Origin and Evolutionary Fate of Recent Gene Retrocopies in Natural Populations of the House Mouse.

Although the contribution of retrogenes to the evolution of genes and genomes has long been recognized, the evolutionary patterns of very recently derived retrocopies that are still polymorphic within natural populations have not been much studied so far. We use here a set of 2,025 such retrocopies in nine house mouse populations from three subspecies (Mus musculus domesticus, M. m. musculus, and M. m. castaneus) to trace their origin and evolutionary fate. We find that ancient house-keeping genes are significantly more likely to generate retrocopies than younger genes and that the propensity to generate a retrocopy depends on its level of expression in the germline. Although most retrocopies are detrimental and quickly purged, we focus here on the subset that appears to be neutral or even adaptive. We show that retrocopies from X-chromosomal parental genes have a higher likelihood to reach elevated frequencies in the populations, confirming the notion of adaptive effects for “out-of-X” retrogenes. Also, retrocopies in intergenic regions are more likely to reach higher population frequencies than those in introns of genes, implying a more detrimental effect when they land within transcribed regions. For a small subset of retrocopies, we find signatures of positive selection, indicating they were involved in a recent adaptation process. We show that the population-specific distribution pattern of retrocopies is phylogenetically informative and can be used to infer population history with a better resolution than with SNP markers.

Contemporary Methods and Evidence for Species Delimitation

Over the last two decades, mitochondrial DNA (mtDNA) sequence data, as well as analyses of nuclear DNA based on the multispecies coalescent model, have increasingly been used to delimit species, sometimes based on limited sampling and without other supporting evidence. We have argued elsewhere that the uncritical use of these approaches has resulted in unnecessary and unwarranted taxonomic changes that have real and long-lasting consequences for science and society. Unfortunately, these arguments have been misrepresented by Burbrink and Ruane's Point of View on “contemporary” species delimitation in this issue. Here, we discuss the role of models in species delimitation research, and again argue that careful consideration of model assumptions (and their potential violation) is necessary when inferring population history and delimiting species. We echo recent calls for targeted, thorough geographic sampling across contact zones and into parapatric ranges to test for reproductive isolation and draw inferences about the evolutionary independence (or lack thereof) of populations that exchange genes. Finally, despite our very different views on how best to identify species and when to make taxonomic changes, we end by highlighting areas where we agree with Burbrink and Ruane's Point of View and offer suggestions for future research.

Contrasting Adult Body-Size in Sister Populations of the Balearic Lizard, Podarcis lilfordi (Günther 1874) Suggests Anthropogenic Selective Pressures

Recently isolated populations offer a good biological model to infer the evolutionary forces responsible for the current divergences across populations. We coupled genetic, morphometric, ecological, and demographic analyses from three island populations of the endemic Balearic Wall Lizard, Podarcis lilfordi, (Balearic archipelago, Spain) to infer the mechanisms underlying the observed differences in body size. For each population, we described plant community structure, derived a biotic capacity index, and used individual-based data on 1369 lizards captured and released during 6 yr (2009–2015) to estimate population density and body growth patterns. We used genetic data collected on 80 individuals (∼27 for each population) to infer genetic divergences across islets and population history. Body size divergences cannot be explained by the ecological or population characteristics. Individual growth was slower in the smallest island, where lizards reached the largest average body size. In addition to having the highest density, results suggested that resource availability does not constrain asymptotic body size, but the speed at which individuals reach it does. The Approximate Bayesian Computation used to infer population history from genetic data supported the occurrence of two bottlenecks in the islet with the highest anthropogenic footprint. We emphasize the need to integrate ecological and genetic data and the importance of considering the effects of past human disturbance as an additional force in being able to model present island fauna.

An instantaneous coalescent method insensitive to population structure

Conventional coalescent inferences of population history make the critical assumption that the population under examination is panmictic. However, most populations are structured. This complicates the prevailing coalescent analyses and sometimes leads to inaccurate estimates. To develop a coalescent method unhampered by population structure, we perform two analyses. First, we demonstrate that the coalescent probability of two randomly sampled alleles from the immediate preceding generation (one generation back) is independent of population structure. Second, motivated by this finding, we propose a new coalescent method: i-coalescent analysis. The i-coalescent analysis computes the instantaneous coalescent rate by using a phylogenetic tree of sampled alleles. Using simulated data, we broadly demonstrate the capability of i-coalescent analysis to accurately reconstruct population size dynamics of highly structured populations, although we find this method often requires larger sample sizes for structured populations than for panmictic populations. Overall, our results indicate i-coalescent analysis to be a useful tool, especially for the inference of population histories with intractable structure such as the developmental history of cell populations in the organs of complex organisms.

Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago

The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 − 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies.

How Many Subpopulations Is Too Many? Exponential Lower Bounds for Inferring Population Histories.

Reconstruction of population histories is a central problem in population genetics. Existing coalescent-based methods, such as the seminal work of Li and Durbin, attempt to solve this problem using sequence data but have no rigorous guarantees. Determining the amount of data needed to correctly reconstruct population histories is a major challenge. Using a variety of tools from information theory, the theory of extremal polynomials, and approximation theory, we prove new sharp information-theoretic lower bounds on the problem of reconstructing population structure-the history of multiple subpopulations that merge, split, and change sizes over time. Our lower bounds are exponential in the number of subpopulations, even when reconstructing recent histories. We demonstrate the sharpness of our lower bounds by providing algorithms for distinguishing and learning population histories with matching dependence on the number of subpopulations. Along the way and of independent interest, we essentially determine the optimal number of samples needed to learn an exponential mixture distribution information-theoretically, proving the upper bound by analyzing natural (and efficient) algorithms for this problem.

A Computational Approach for Modeling the Allele Frequency Spectrum of Populations with Arbitrarily Varying Size

The allele frequency spectrum (AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural selection. In 2013, Chen and Chen developed a method for analytically deriving the AFS for populations with temporally varying size through the coalescence time-scaling function. However, their approach is only applicable to population history scenarios in which the analytical form of the time-scaling function is tractable. In this paper, we propose a computational approach to extend the method to populations with arbitrary complex varying size by numerically approximating the time-scaling function. We demonstrate the performance of the approach by constructing the AFS for two population history scenarios: the logistic growth model and the Gompertz growth model, for which the AFS are unavailable with existing approaches. Software for implementing the algorithm can be downloaded at http://chenlab.big.ac.cn/software/.

Inference of complex population histories using whole-genome sequences from multiple populations

There has been much interest in analyzing genome-scale DNA sequence data to infer population histories, but inference methods developed hitherto are limited in model complexity and computational scalability. Here we present an efficient, flexible statistical method, diCal2, that can use whole-genome sequence data from multiple populations to infer complex demographic models involving population size changes, population splits, admixture, and migration. Applying our method to data from Australian, East Asian, European, and Papuan populations, we find that the population ancestral to Australians and Papuans started separating from East Asians and Europeans about 100,000 y ago, and that the separation of East Asians and Europeans started about 50,000 y ago, with pervasive gene flow between all pairs of populations.

The Rise and Fall of BritainsDNA: A Tale of Misleading Claims, Media Manipulation and Threats to Academic Freedom

Direct-to-consumer genetic ancestry testing is a new and growing industry that has gained widespread media coverage and public interest. Its scientific base is in the fields of population and evolutionary genetics and it has benefitted considerably from recent advances in rapid and cost-effective DNA typing technologies. There is a considerable body of scientific literature on the use of genetic data to make inferences about human population history, although publications on inferring the ancestry of specific individuals are rarer. Population geneticists have questioned the scientific validity of some population history inference approaches, particularly those of a more interpretative nature. These controversies have spilled over into commercial genetic ancestry testing, with some companies making sensational claims about their products. One such company—BritainsDNA—made a number of dubious claims both directly to its customers and in the media. Here we outline our scientific concerns, document the exchanges between us, BritainsDNA and the BBC, and discuss the issues raised about media promotion of commercial enterprises, academic freedom of expression, science and pseudoscience and the genetic ancestry testing industry. We provide a detailed account of this case as a resource for historians and sociologists of science, and to shape public understanding, media reporting and scientific scrutiny of the commercial use of population and evolutionary genetics.

Inference of multiple-wave admixtures by length distribution of ancestral tracks.

The ancestral tracks in admixed genomes are valuable for population history inference. While a few methods have been developed to infer admixture history based on ancestral tracks, these methods suffer the same flaw: only population admixture history under some specific models can be inferred. In addition, the inference of history might be biased or even unreliable if the specific model deviates from the real situation. To address this problem, we firstly proposed a general discrete admixture model to describe the admixture history with multiple ancestral populations and multiple-wave admixtures. We next deduced the length distribution of ancestral tracks under the general discrete admixture model. We further developed a new method, MultiWaver, to explore multiple-wave admixture histories. Our method could automatically determine an optimal admixture model based on the length distribution of ancestral tracks, and estimate the corresponding parameters under this optimal model. Specifically, we used a likelihood ratio test (LRT) to determine the number of admixture waves, and implemented an expectation-maximization (EM) algorithm to estimate parameters. We used simulation studies to validate the reliability and effectiveness of our method. Finally, good performance was observed when our method was applied to real data sets of African Americans and Mexicans, and new insights were gained into the admixture history of Uyghurs and Hazaras.

Lack of allozyme variation in the two carnivorous, terrestrial herbs Utricularia bifida and Utricularia caerulea (Lentibulariaceae) co-occurring on wetlands in South Korea: Inference of population history

This research was supported by Basic Science Program through the National Research Foundation of Korea (NRF-2017R1A2B4012215) funded by the Ministry of Education, Science and Technology to M.G.C.

Tournament ABC analysis of the western Palaearctic population history of an oak gall wasp, Synergus umbraculus.

Approximate Bayesian computation (ABC) is a powerful and widely used approach in inference of population history. However, the computational effort required to discriminate among alternative historical scenarios often limits the set that is compared to those considered more likely a priori. While often justifiable, this approach will fail to consider unexpected but well-supported population histories. We used a hierarchical tournament approach, in which subsets of scenarios are compared in a first round of ABC analyses and the winners are compared in a second analysis, to reconstruct the population history of an oak gall wasp, Synergus umbraculus (Hymenoptera, Cynipidae) across the Western Palaearctic. We used 4,233bp of sequence data across seven loci to explore the relationships between four putative Pleistocene refuge populations in Iberia, Italy, the Balkans and Western Asia. We compared support for 148 alternative scenarios in eight pools, each pool comprising all possible rearrangements of four populations over a given topology of relationships, with or without founding of one population by admixture and with or without an unsampled "ghost" population. We found very little support for the directional "out of the east" scenario previously inferred for other gall wasp community members. Instead, the best-supported models identified Iberia as the first-regional population to diverge from the others in the late Pleistocene, followed by divergence between the Balkans and Western Asia, and founding of the Italian population through late Pleistocene admixture from Iberia and the Balkans. We compare these results with what is known for other members of the oak gall community, and consider the strengths and weaknesses of using a tournament approach to explore phylogeographic model space.

Screening chloroplast regions in Calophyllum brasiliense (Calophyllaceae) for suitability for population genetic analyses

The uniparental inheritance and conserved structure of the chloroplast genome among many angiosperms makes it suitable for constructing gene lineages and inferring population histories based on these relationships. However, the analysis of a single chloroplast region to solve population issues has not yielded the desired amount of variability due to the low mutation rate. Therefore, it is necessary to screen and carefully analyze chloroplast intergenic or intronic regions to select the most appropriate for studying the genetic variability in the chloroplast genome of a particular taxon. In this context, the aim of this work was to characterize 8 regions in Calophyllum brasiliense using 11 selected primer pairs and to evaluate their usefulness for phylogeographic analysis. Intergenic spacers petA-psbJ, petG-trnP and rpl32-trnL and the trnL intron demonstrated potentially informative sites. The combination of these 4 regions will allow the analysis of genetic population structure and the integration of historical aspects to inform strategies for conserving C. brasiliense, especially for highly impacted populations and those at risk of local extinction.