Myriam Georges

Sex-Specific Genetic Structure and Social Organization in Central Asia: Insights from a Multi-Locus Study

In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining portion of the Y chromosome (NRY) have been extensively used in order to measure the maternally and paternally inherited genetic structure of human populations, and to infer sex-specific demography and history. Most studies converge towards the notion that among populations, women are genetically less structured than men. This has been mainly explained by a higher migration rate of women, due to patrilocality, a tendency for men to stay in their birthplace while women move to their husbands house. Yet, since population differentiation depends upon the product of the effective number of individuals within each deme and the migration rate among demes, differences in male and female effective numbers and sex-biased dispersal have confounding effects on the comparison of genetic structure as measured by uniparentally inherited markers. In this study, we develop a new multi-locus approach to analyze jointly autosomal and X-linked markers in order to aid the understanding of sex-specific contributions to population differentiation. We show that in patrilineal herder groups of Central Asia, in contrast to bilineal agriculturalists, the effective number of women is higher than that of men. We interpret this result, which could not be obtained by the analysis of mtDNA and NRY alone, as the consequence of the social organization of patrilineal populations, in which genetically related men (but not women) tend to cluster together. This study suggests that differences in sex-specific migration rates may not be the only cause of contrasting male and female differentiation in humans, and that differences in effective numbers do matter.

Sociocultural Behavior, Sex-Biased Admixture, and Effective Population Sizes in Central African Pygmies and Non-Pygmies

Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography. In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter-gatherer Pygmies and sedentary agricultural non-Pygmies. However, their sex-specific demography remains largely unknown. Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers. We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups. We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies. Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations. In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies. Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages. Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context. We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.

Lactase Persistence in Central Asia: Phenotype, Genotype, and Evolution

Abstract The aim of the present study is to document the evolution of the lactase persistence trait in Central Asia, a geographical area that is thought to have been a region of long-term pastoralism. Several ethnic groups co-exist in this area: Indo-Iranian speakers who are traditionally agriculturist (Tajik) and Turkic speakers who used to be nomadic herders (Kazakh, Karakalpak, Kyrgyz, Turkmen). It was recently demonstrated that horse milking practice existed in the Botai culture of Kazakhstan as early as 5,500 BP (Outram et al. 2009). However, the frequency of the lactase persistence trait and its genetic basis in Central Asian populations remain largely unknown. We propose here the first genotype-phenotype study of lactase persistence in Central Asia based on 183 individuals, as well as the estimation of the time of expansion of the lactase-persistence associated polymorphism. Our results show a remarkable genetic-phenotypic correlation, with the causal polymorphism being the same than in Europe (-13.910C>T, rs4988235). The lactase persistence trait is at low frequency in these populations: between 25% and 32% in the Kazakh population (traditionally herders), according to phenotype used, and between 11% and 30% in the Tajiko-Uzbek population (agriculturalists). The difference in lactase persistence between populations, even if small, is significant when using individuals concordant for both excretion of breath hydrogen and the lactose tolerance blood glucose test phenotypes (P = 0.018, 25% for Kazakh vs. 11% for Tajiko-Uzbeks), and the difference in frequency of the -13.910*T allele is almost significant (P = 0.06, 30% for Kazakhs vs. 19% for Tajiko-Uzbeks). Using the surrounding haplotype, we estimate a date of expansion of the T allele around 6,000–12,000 yrs ago, which is consistent with archaeological records for the emergence of agropastoralism and pastoralism in Central Asia.

In the heartland of Eurasia: the multilocus genetic landscape of Central Asian populations

Located in the Eurasian heartland, Central Asia has played a major role in both the early spread of modern humans out of Africa and the more recent settlements of differentiated populations across Eurasia. A detailed knowledge of the peopling in this vast region would therefore greatly improve our understanding of range expansions, colonizations and recurrent migrations, including the impact of the historical expansion of eastern nomadic groups that occurred in Central Asia. However, despite its presumable importance, little is known about the level and the distribution of genetic variation in this region. We genotyped 26 Indo-Iranian- and Turkic-speaking populations, belonging to six different ethnic groups, at 27 autosomal microsatellite loci. The analysis of genetic variation reveals that Central Asian diversity is mainly shaped by linguistic affiliation, with Turkic-speaking populations forming a cluster more closely related to East-Asian populations and Indo-Iranian speakers forming a cluster closer to Western Eurasians. The scattered position of Uzbeks across Turkic- and Indo-Iranian-speaking populations may reflect their origins from the union of different tribes. We propose that the complex genetic landscape of Central Asian populations results from the movements of eastern, Turkic-speaking groups during historical times, into a long-lasting group of settled populations, which may be represented nowadays by Tajiks and Turkmen. Contrary to what is generally thought, our results suggest that the recurrent expansions of eastern nomadic groups did not result in the complete replacement of local populations, but rather into partial admixture.

Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia.

The high prevalence of type 2 diabetes and its uneven distribution among human populations is both a major public health concern and a puzzle in evolutionary biology. Why is this deleterious disease so common, while the associated genetic variants should be removed by natural selection? The ‘thrifty genotype’ hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. In this study, we characterized patterns of selection at 10 variants associated with type 2 diabetes, contrasting one herder and one farmer population from Central Asia. We aimed at identifying which alleles (risk or protective) are under selection, dating the timing of selective events, and investigating the effect of lifestyle on selective patterns. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants.

Genetic Diversity of Four Filipino Negrito Populations from Luzon: Comparison of Male and Female Effective Population Sizes and Differential Integration of Immigrants into Aeta and Agta Communities

Abstract Genetic data corresponding to four negrito populations (two Aeta and two Agta; n = 120) from the Luzon region of the Philippines have been analyzed. These data comprise mitochondrial DNA (mtDNA) hypervariable segment 1 haplotypes and haplogroups, Y-chromosome haplogroups and short tandem repeats (STRs), autosomal STRs, and X-chromosome STRs. The genetic diversity and structure of the populations were investigated at a local, regional, and interregional level. We found a high level of autosomal differentiation, combined with no significant reduction in diversity, consistent with long-term settlement of the Luzon region by the ancestors of the Agta and Aeta followed by reduced gene flow between these two ethnolinguistic groups. Collectively, the Aeta have a much higher ratio of female:male effective population size than do the Agta, a finding that supports phylogenetic analysis of their mtDNA and Y-chromosome haplogroups, which suggests different genetic sex-biased contributions from putative Austronesian source populations. We propose that factors of social organization that led to the reduction in Agta female effective population size may also be linked to the limited incorporation of female lineages associated with the settlement of the Philippines by Austronesian speakers; conversely, the reduction in Aeta male effective population size, relative to females, could be indicative of a limited incorporation of male lineages associated with this demographic process.

The role of GHR and IGF1 genes in the genetic determination of African pygmies' short stature.

African pygmies are at the lower extreme of human variation in adult stature and many evolutionary hypotheses have been proposed to explain this phenotype. We showed in a recent study that the difference in average stature of about 10 cm observed between contemporary pygmies and neighboring non-pygmies has a genetic component. Nevertheless, the genetic basis of African pygmies’ short stature remains unknown. Using a candidate-gene approach, we show that intronic polymorphisms in GH receptor (GHR) and insulin-like growth factor 1 (IGF1) genes present outlying values of the genetic distance between Baka pygmies and their non-pygmy Nzimé neighbors. We further show that GHR and IGF1 genes have experienced divergent natural selection pressures between pygmies and non-pygmies throughout evolution. In addition, these SNPs are associated with stature in a sample composed of 60 pygmies and 30 non-pygmies and this association remains significant when correcting for population structure for the GHR locus. We conclude that the GHR and IGF1 genes may have a role in African pygmies’ short stature. The use of phenotypically contrasted populations is a promising strategy to identify new variants associated with complex traits in humans.

Ancestry and demography and descendants of Iron Age nomads of the Eurasian Steppe

During the 1st millennium before the Common Era (BCE), nomadic tribes associated with the Iron Age Scythian culture spread over the Eurasian Steppe, covering a territory of more than 3,500 km in breadth. To understand the demographic processes behind the spread of the Scythian culture, we analysed genomic data from eight individuals and a mitochondrial dataset of 96 individuals originating in eastern and western parts of the Eurasian Steppe. Genomic inference reveals that Scythians in the east and the west of the steppe zone can best be described as a mixture of Yamnaya-related ancestry and an East Asian component. Demographic modelling suggests independent origins for eastern and western groups with ongoing gene-flow between them, plausibly explaining the striking uniformity of their material culture. We also find evidence that significant gene-flow from east to west Eurasia must have occurred early during the Iron Age.

Sex‐specific genetic diversity is shaped by cultural factors in Inner Asian human populations

OBJECTIVES Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. METHODS We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. RESULTS Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. CONCLUSIONS This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure.

Cultivation of an immobilized (hyper)thermophilic marine microbial community in a bioreactor

Cultivation in a bioreactor of immobilized deep-sea hydrothermal microbial community was tested in order to assess the stability and reactivity of this new system. A community composed of eight hydrothermal strains was entrapped in a polymer matrix that was used to inoculate a continuous culture in a gas-lift bioreactor. The continuous culture was performed for 41 days at successively 60°C, 55°C, 60°C, 85°C and 60°C, at pH 6.5, in anaerobic condition and constant dilution rate. Oxic stress and pH variations were tested at the beginning of the incubation. Despite these detrimental conditions, three strains including two strict anaerobes were maintained in the bioreactor. High cell concentrations (3 × 10(8) cells mL(-1)) and high ATP contents were measured in both liquid fractions and beads. Cloning-sequencing and qPCR revealed that Bacillus sp. dominated at the early stage, and was later replaced by Thermotoga maritima and Thermococcus sp. Acetate, formate and propionate concentrations varied simultaneously in the liquid fractions. These results demonstrate that these immobilized cells were reactive to culture conditions. They were protected inside the beads during the stress period and released in the liquid fraction when conditions were more favorable. This confirms the advantage of immobilization that highlights the resilience capacity of certain hydrothermal microorganisms after a stress period.