Cultural transmission of reproductive success impacts genomic diversity, coalescent tree topologies, and demographic inferences.

Cultural transmission of reproductive success has been observed in many human populations as well as other animals. Cultural transmission of reproductive success consists of a positive correlation of nongenetic origin between the progeny size of parents and children. This correlation can result from various factors, such as the social influence of parents on their children, the increase of children's survival through allocare from uncles and aunts, or the transmission of resources. Here, we study the evolution of genomic diversity over time under cultural transmission of reproductive success. Cultural transmission of reproductive success has a threefold impact on population genetics: (1) the effective population size decreases when cultural transmission of reproductive success starts, mimicking a population contraction, and increases back to its original value when cultural transmission of reproductive success stops; (2) coalescent tree topologies are distorted under cultural transmission of reproductive success, with higher imbalance and a higher number of polytomies; and (3) branch lengths are reduced nonhomogenously, with a higher impact on older branches. Under long-lasting cultural transmission of reproductive success, the effective population size stabilizes but the distortion of tree topology and the nonhomogenous branch length reduction remain, yielding U-shaped site frequency spectra under a constant population size. We show that this yields a bias in site frequency spectra-based demographic inference. Considering that cultural transmission of reproductive success was detected in numerous human and animal populations worldwide, one should be cautious because inferring population past histories from genomic data can be biased by this cultural process.

No evidence for female kin association, indications for extragroup paternity, and sex-biased dispersal patterns in wild western gorillas.

Characterizing animal dispersal patterns and the rational behind individuals' transfer choices is a long-standing question of interest in evolutionary biology. In wild western gorillas (Gorilla gorilla), a one-male polygynous species, previous genetic findings suggested that, when dispersing, females might favor groups with female kin to promote cooperation, resulting in higher-than-expected within-group female relatedness. The extent of male dispersal remains unclear with studies showing conflicting results. To investigate male and female dispersal patterns and extragroup paternity, we analyzed long-term field observations, including female spatial proximity data, together with genetic data (10 autosomal microsatellites) on individuals from a unique set of four habituated western gorilla groups, and four additional extragroup males (49 individuals in total). The majority of offspring (25 of 27) were sired by the group male. For two offspring, evidence for extragroup paternity was found. Contrarily to previous findings, adult females were not significantly more related within groups than across groups. Consistently, adult female relatedness within groups did not correlate with their spatial proximity inferred from behavioral data. Adult females were similarly related to adult males from their group than from other groups. Using R ST statistics, we found significant genetic structure and a pattern of isolation by distance, indicating limited dispersal in this species. Comparing relatedness among females and among males revealed that males disperse farer than females, as expected in a polygamous species. Our study on habituated western gorillas shed light on the dispersal dynamics and reproductive behavior of this polygynous species and challenge some of the previous results based on unhabituated groups.

Polygenic Adaptation: Integrating Population Genetics and Gene Regulatory Networks.

The adaptation of populations to local environments often relies on the selection of optimal values for polygenic traits. Here, we first summarize the results obtained from different quantitative genetics and population genetics models, about the genetic architecture of polygenic traits and their response to directional selection. We then highlight the contribution of systems biology to the understanding of the molecular bases of polygenic traits and the evolution of gene regulatory networks involved in these traits. Finally, we discuss the need for a unifying framework merging the fields of population genetics, quantitative genetics and systems biology to better understand the molecular bases of polygenic traits adaptation.

Sahelian pastoralism from the perspective of variants associated with lactase persistence.

OBJECTIVES: Archeological evidence shows that first nomadic pastoralists came to the African Sahel from northeastern Sahara, where milking is reported by ~7.5 ka. A second wave of pastoralists arrived with the expansion of Arabic tribes in 7th-14th century CE. All Sahelian pastoralists depend on milk production but genetic diversity underlying their lactase persistence (LP) is poorly understood. MATERIALS AND METHODS: We investigated SNP variants associated with LP in 1,241 individuals from 29 mostly pastoralist populations in the Sahel. Then, we analyzed six SNPs in the neighboring fragment (419 kb) in the Fulani and Tuareg with the -13910*T mutation, reconstructed haplotypes, and calculated expansion age and growth rate of this variant. RESULTS: Our results reveal a geographic localization of two different LP variants in the Sahel: -13910*T west of Lake Chad (Fulani and Tuareg pastoralists) and -13915*G east of there (mostly Arabic-speaking pastoralists). We show that -13910*T has a more diversified haplotype background among the Fulani than among the Tuareg and that the age estimate for expansion of this variant among the Fulani (~8.5 ka) corresponds to introduction of cattle to the area. CONCLUSIONS: This is the first study showing that the "Eurasian" LP allele -13910*T is widespread both in northern Europe and in the Sahel; however, it is limited to pastoralists in the Sahel. Since the Fulani haplotype with -13910*T is shared with contemporary Eurasians, its origin could be in a region encompassing the Near East and northeastern Africa in a population ancestral to both Saharan pastoralists and European farmers.

The Genetic Architecture of Chronic Mountain Sickness in Peru.

Chronic mountain sickness (CMS) is a pathological condition resulting from chronic exposure to high-altitude hypoxia. While its prevalence is high in native Andeans (>10%), little is known about the genetic architecture of this disease. Here, we performed the largest genome-wide association study (GWAS) of CMS (166 CMS patients and 146 controls living at 4,380 m in Peru) to detect genetic variants associated with CMS. We highlighted four new candidate loci, including the first CMS-associated variant reaching GWAS statistical significance (rs7304081; P = 4.58 × 10-9). By looking at differentially expressed genes between CMS patients and controls around these four loci, we suggested AEBP2, CAST, and MCTP2 as candidate CMS causal genes. None of the candidate loci were under strong natural selection, consistent with the observation that CMS affects fitness mainly after the reproductive years. Overall, our results reveal new insights on the genetic architecture of CMS and do not provide evidence that CMS-associated variants are linked to a strong ongoing adaptation to high altitude.

An ABC Method for Whole-Genome Sequence Data: Inferring Paleolithic and Neolithic Human Expansions.

Species generally undergo a complex demographic history consisting, in particular, of multiple changes in population size. Genome-wide sequencing data are potentially highly informative for reconstructing this demographic history. A crucial point is to extract the relevant information from these very large data sets. Here, we design an approach for inferring past demographic events from a moderate number of fully sequenced genomes. Our new approach uses Approximate Bayesian Computation, a simulation-based statistical framework that allows 1) identifying the best demographic scenario among several competing scenarios and 2) estimating the best-fitting parameters under the chosen scenario. Approximate Bayesian Computation relies on the computation of summary statistics. Using a cross-validation approach, we show that statistics such as the lengths of haplotypes shared between individuals, or the decay of linkage disequilibrium with distance, can be combined with classical statistics (e.g., heterozygosity and Tajima's D) to accurately infer complex demographic scenarios including bottlenecks and expansion periods. We also demonstrate the importance of simultaneously estimating the genotyping error rate. Applying our method on genome-wide human-sequence databases, we finally show that a model consisting in a bottleneck followed by a Paleolithic and a Neolithic expansion is the most relevant for Eurasian populations.

An evaluation of the methods to estimate effective population size from measures of linkage disequilibrium.

In 1971, John Sved derived an approximate relationship between linkage disequilibrium (LD) and effective population size for an ideal finite population. This seminal work was extended by Sved and Feldman (Theor Pop Biol 4, 129, 1973) and Weir and Hill (Genetics 95, 477, 1980) who derived additional equations with the same purpose. These equations yield useful estimates of effective population size, as they require a single sample in time. As these estimates of effective population size are now commonly used on a variety of genomic data, from arrays of single nucleotide polymorphisms to whole genome data, some authors have investigated their bias through simulation studies and proposed corrections for different mating systems. However, the cause of the bias remains elusive. Here, we show the problems of using LD as a statistical measure and, analogously, the problems in estimating effective population size from such measure. For that purpose, we compare three commonly used approaches with a transition probability-based method that we develop here. It provides an exact computation of LD. We show here that the bias in the estimates of LD and effective population size are partly due to low-frequency markers, tightly linked markers or to a small total number of crossovers per generation. These biases, however, do not decrease when increasing sample size or using unlinked markers. Our results show the issues of such measures of effective population based on LD and suggest which of the method here studied should be used in empirical studies as well as the optimal distance between markers for such estimates.

Neutral Theory: From Complex Population History to Natural Selection and Sociocultural Phenomena in Human Populations.

Here, we present a synthetic view on how Kimura's Neutral theory has helped us gaining insight on the different evolutionary forces that shape human evolution. We put this perspective in the frame of recent emerging challenges: the use of whole genome data for reconstructing population histories, natural selection on complex polygenic traits, and integrating cultural processes in human evolution.

Cryptic Biological Invasions: a General Model of Hybridization.

The dispersal of non-native genes due to hybridization is a form of cryptic invasion with growing concern in evolution and conservation. This includes the spread of transgenic genes and antibiotic resistance. To investigate how genes and phenotypes are transmitted, we developed a general model that, for the first time, considers concurrently: multiple loci, quantitative and qualitative gene expression, assortative mating, dominance/recessivity inheritance and density-dependent demographic effects. Selection acting on alleles or genotypes can also be incorporated. Our results reveal that the conclusions about how hybridization threatens a species can be biased if they are based on single-gene models, while considering two or more genes can correct this bias. We also show that demography can amplify or balance the genetic effects, evidencing the need of jointly incorporating both processes. By implementing our model in a real case, we show that mallard ducks introduced in New Zealand benefit from hybridization to replace native grey-ducks. Total displacement can take a few generations and occurs by interspecific competition and by competition between hybrids and natives, demonstrating how hybridization may facilitate biological invasions. We argue that our general model represents a powerful tool for the study of a wide range of biological and societal questions.

Trait level analysis of multitrait population projection matrices.

In most matrix population projection models, individuals are characterized according to, usually, one or two traits such as age, stage, size or location. A broad theory of multitrait population projection matrices (MPPMs) incorporating larger number of traits was long held back by time and space computational complexity issues. As a consequence, no study has yet focused on the influence of the structure of traits describing a life-cycle on population dynamics and life-history evolution. We present here a novel vector-based MPPM building methodology that allows to computationally-efficiently model populations characterized by numerous traits with large distributions, and extend sensitivity analyses for these models. We then present a new method, the trait level analysis consisting in folding an MPPM on any of its traits to create a matrix with alternative trait structure (the number of traits and their characteristics) but similar asymptotic properties. Adding or removing one or several traits to/from the MPPM and analyzing the resulting changes in spectral properties, allows investigating the influence of the trait structure on the evolution of traits. We illustrate this by modeling a 3-trait (age, parity and fecundity) population designed to investigate the implications of parity-fertilitytrade-offs in a context of fecundity heterogeneity in humans. The trait level analysis, comparing models of the same population differing in trait structures, demonstrates that fertility selection gradients differ between cases with or without parity-fertility trade-offs. Moreover it shows that age-specific fertility has seemingly very different evolutionary significance depending on whether heterogeneity is accounted for. This is because trade-offs can vary strongly in strength and even direction depending on the trait structure used to model the population.

Genetic and linguistic histories in Central Asia inferred using approximate Bayesian computations.

Linguistic and genetic data have been widely compared, but the histories underlying these descriptions are rarely jointly inferred. We developed a unique methodological framework for analysing jointly language diversity and genetic polymorphism data, to infer the past history of separation, exchange and admixture events among human populations. This method relies on approximate Bayesian computations that enable the identification of the most probable historical scenario underlying each type of data, and to infer the parameters of these scenarios. For this purpose, we developed a new computer program PopLingSim that simulates the evolution of linguistic diversity, which we coupled with an existing coalescent-based genetic simulation program, to simulate both linguistic and genetic data within a set of populations. Applying this new program to a wide linguistic and genetic dataset of Central Asia, we found several differences between linguistic and genetic histories. In particular, we showed how genetic and linguistic exchanges differed in the past in this area: some cultural exchanges were maintained without genetic exchanges. The methodological framework and the linguistic simulation tool developed here can be used in future work for disentangling complex linguistic and genetic evolutions underlying human biological and cultural histories.

The historical spread of Arabian Pastoralists to the eastern African Sahel evidenced by the lactase persistence -13,915*G allele and mitochondrial DNA.

OBJECTIVES: Thanks to the ability to digest lactose, Arabian nomads had become less dependent upon their sedentary neighbors and some of these populations spread to Africa. When and by which route they migrated to their current locations have previously been addressed only by historical and archaeological data. METHODS: To address the question of Arab expansion into Africa, we collected samples from several Arabic populations, especially the Baggara in Chad and Sudan. We analyzed mutations associated with lactase persistence and reconstructed the surrounding haplotypes defined by SNP polymorphisms. We also sequenced their mitochondrial DNA to investigate relative proportions of sub-Saharan and Eurasian origins. RESULTS: We estimated the expansion age of the -13,915*G mutation in four different Arabian datasets. The oldest age was identified in Yemen (1,356-1,799 ya) and the youngest in a Sudanese group of Rashaayda Arabs (219-312 ya). We also found a negative correlation between the frequency of the -13,915*G allele and the frequency of sub-Saharan mtDNA haplotypes. CONCLUSIONS: Even if the age of the most recent common ancestor of -13,915*G is ∼4 ka as shown in a previous study, our results suggest that its spread to Africa was more recent, which is consistent with the migrations of Arabic tribes. Because the incidence of sub-Saharan mtDNA haplotypes is negatively correlated with the occurrence of -13,915*G, we suggest that the decrease of its frequency in Africa has been caused by progressive admixture of the Arabian nomads with sub-Saharan populations.

Different kinds of genetic markers permit inference of Paleolithic and Neolithic expansions in humans.

Recent population genetic studies have provided valuable insights on the demographic history of our species. However, some issues such as the dating of the first demographic expansions in human populations remain puzzling. Indeed, although a few genetic studies argued that the first human expansions were concomitant with the Neolithic transition, many others found signals of expansion events starting during the Palaeolithic. Here we performed a simulation study to show that these contradictory findings may result from the differences in the genetic markers used, especially if two successive expansion events occurred. For a large majority of replicates for each scenario tested, microsatellite data allow only detecting the recent expansion event in that case, whereas sequence data allow only detecting the ancient expansion. Combined with previous real data analyses, our results bring support to the ideas that (i) a first human expansions started during the Palaeolithic period, (ii) a second expansion event occurred later, concomitantly with the Neolithic transition.

Inferring Population Size History from Large Samples of Genome-Wide Molecular Data - An Approximate Bayesian Computation Approach.

Inferring the ancestral dynamics of effective population size is a long-standing question in population genetics, which can now be tackled much more accurately thanks to the massive genomic data available in many species. Several promising methods that take advantage of whole-genome sequences have been recently developed in this context. However, they can only be applied to rather small samples, which limits their ability to estimate recent population size history. Besides, they can be very sensitive to sequencing or phasing errors. Here we introduce a new approximate Bayesian computation approach named PopSizeABC that allows estimating the evolution of the effective population size through time, using a large sample of complete genomes. This sample is summarized using the folded allele frequency spectrum and the average zygotic linkage disequilibrium at different bins of physical distance, two classes of statistics that are widely used in population genetics and can be easily computed from unphased and unpolarized SNP data. Our approach provides accurate estimations of past population sizes, from the very first generations before present back to the expected time to the most recent common ancestor of the sample, as shown by simulations under a wide range of demographic scenarios. When applied to samples of 15 or 25 complete genomes in four cattle breeds (Angus, Fleckvieh, Holstein and Jersey), PopSizeABC revealed a series of population declines, related to historical events such as domestication or modern breed creation. We further highlight that our approach is robust to sequencing errors, provided summary statistics are computed from SNPs with common alleles.

Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations.

Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations--a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants--c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.

Using genome-wide measures of coancestry to maintain diversity and fitness in endangered and domestic pig populations.

Conservation and breeding programs aim at maintaining the most diversity, thereby avoiding deleterious effects of inbreeding while maintaining enough variation from which traits of interest can be selected. Theoretically, the most diversity is maintained using optimal contributions based on many markers to calculate coancestries, but this can decrease fitness by maintaining linked deleterious variants. The heterogeneous patterns of coancestry displayed in pigs make them an excellent model to test these predictions. We propose methods to measure coancestry and fitness from resequencing data and use them in population management. We analyzed the resequencing data of Sus cebifrons, a highly endangered porcine species from the Philippines, and genotype data from the Pietrain domestic breed. By analyzing the demographic history of Sus cebifrons, we inferred two past bottlenecks that resulted in some inbreeding load. In Pietrain, we analyzed signatures of selection possibly associated with commercial traits. We also simulated the management of each population to assess the performance of different optimal contribution methods to maintain diversity, fitness, and selection signatures. Maximum genetic diversity was maintained using marker-by-marker coancestry, and least using genealogical coancestry. Using a measure of coancestry based on shared segments of the genome achieved the best results in terms of diversity and fitness. However, this segment-based management eliminated signatures of selection. We demonstrate that maintaining both diversity and fitness depends on the genomic distribution of deleterious variants, which is shaped by demographic and selection histories. Our findings show the importance of genomic and next-generation sequencing information in the optimal design of breeding or conservation programs.

Patrilineal populations show more male transmission of reproductive success than cognatic populations in Central Asia, which reduces their genetic diversity.

OBJECTIVE: The extent to which social organization of human societies impacts the patterns of genetic diversity remains an open question. Here, we investigate the transmission of reproductive success in patrilineal and cognatic populations from Central Asia using a coalescent approach. METHODS: We performed a study on the mitochondrial DNA (mtDNA) and Y chromosome polymorphism of patrilineal and cognatic populations from Central Asia. We reconstructed the gene genealogies in each population for both kind of markers and inferred the imbalance level of these genealogies, a parameter directly related to the level of transmission of reproductive success. RESULTS: This imbalance level appeared much stronger for the Y chromosome in patrilineal populations than in cognatic populations, while no difference was found for mtDNA. Furthermore, we showed that this imbalance level correlates negatively with Y-chromosomal, mtDNA, and autosomal genetic diversity. CONCLUSIONS: This shows that patrilineality might be one of the factors explaining the male transmission of reproductive success, which, in turn, lead to a reduction of genetic diversity. Thus, notwithstanding the fact that our population genetic approach clearly shows that there is a strong male-biased transmission of reproductive success in patrilineal societies, it also highlights the fact that a social process such as cultural transmission of reproductive success could play an important role in shaping human genetic diversity, although we cannot formally exclude that this transmission has also a genetic component.