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 husband's 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

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

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 lactasepersistence associated polymorphism. Our results show a remarkable geneticphenotypic 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

Human sex-specific demography inferred from genetic data.

<p>This table summarizes the observed patterns of sex-specific differences in demographic parameters reported in a number of recent studies. The first column lists the location of the sampled populations, or indicates whether the study is conducted at a global scale. The second column gives the markers used, and the third column indicates the statistical methods employed. The fourth column provides indications on social organization, available a priori for the populations under study. In the fifth and sixth columns, the authors' interpretations of sex-specific differences in demographic parameters are given, with respect to skewed gene flow and/or effective numbers.</p>a<p>Indications on social organization, marriage rules, etc., as provided by the authors.</p>b<p>The differences in demographic parameters between males and females, as inferred by the authors, are given in terms of sex-biased gene flow, and skewed effective numbers; the authors' interpretation to the observed pattern is given in parentheses, when available.</p>c<p>Single nucleotide polymorphisms.</p>d<p>Analysis of molecular variance <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Excoffier2" target="_blank">[69]</a>.</p>e<p>Not available (no detailed information given by the authors concerning social organization, marriage rules, etc.).</p>f<p>Short tandem repeats.</p>g<p>Time to the most recent common ancestor.</p>h<p>mtDNA and NRY were not sampled in the same individuals or populations.</p>i<p>The authors discussed a possible difference in demographic parameters between males and females, but considered it as negligible.</p>j<p>The authors did not consider this pattern.</p>k<p>Food-producer populations.</p>l<p>Hunter-gatherer populations.</p>m<p>Monte Carlo Markov chain method to estimate population sizes and migration rates <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Beerli1" target="_blank">[70]</a>.</p>n<p>Variance in Reproductive Success.</p>o<p>population-mutation parameter.</p

<i>p</i>-values of Wilcoxon tests plotted in the (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) parameter space.

<p>For each set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values, we applied the transformation in eq. (4), and tested whether our data on autosomal and X-linked markers were consistent, given the hypothesis defined by the set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values. (A) Surface plot of the <i>p</i>-values, as a function of the female fraction of effective number and the female fraction of migration rate, for the herders (11 populations). The arrow indicates the line that separates the region where <i>p</i>≤0.05 from that where <i>p</i>>0.05. Non-significant <i>p</i>-values (<i>p</i>>0.05) correspond to the values of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) that could not be rejected, given our data. (B) Contour plots, for the same data. The dashed line indicates the range of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values inferred from the ratio of NRY and mtDNA population structure, as obtained from the relationship: . The dotted lines correspond to the cases where <i>N</i>_f = <i>N</i>_m (vertical line) and <i>m</i>_f = <i>m</i>_m (horizontal line). (C) and (D) as (A) and (B), respectively, for the agriculturalists (10 populations).</p

Geographic map of the sampled area, with the 21 populations studied.

<p>Bilineal agriculturalist populations are in blue (Tajiks); Patrilineal herders with a semi-nomadic lifestyle are in red (Kazaks, Karakalpaks, Kyrgyz and Turkmen).</p

Sample description.

<p>Long., longitude; Lat., latitude. <i>n</i>_X, <i>n</i>_A, <i>n</i>_Y and <i>n</i>_mt: sample size for X-linked, autosomal, Y-linked and mitochondrial markers, respectively.</p

Percentage of significant tests in the (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) parameter space, for simulated data.

<p>We chose a range of 49 (<i>N</i>_f<i>m</i>_f/<i>N</i>_m<i>m</i>_m) ratios, varying from 0.0004 to 2401, and for each of these ratios we chose 29 sets of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values. By doing this, we obtained 1421 sets of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values, represented as white dots in the right-hand side panel B, covering the whole parameter space. For each set, we simulated 100 independent datasets using a coalescent-based algorithm, and taking the same number of individuals and the same number of loci for each genetic system as in the observed data. For each dataset, we calculated the <i>p</i>-value for a one-sided Wilcoxon sum rank test , and for each set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values we calculated the percentage of significant <i>p</i>-values (at the <i>α</i> = 0.05 level). A. Surface plot of the proportion of significant <i>p</i>-values (at the <i>α</i> = 0.05 level), as a function of the female fraction of effective number and the female fraction of migration rate. B. Contour plot, for the same data. The dotted line, at which , represents the set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values where the autosomal and X-linked <i>F</i>_ST's are equal. The theory predicts that we should only find in the upper-right triangle defined by the dotted line. Hence, the proportion of significant <i>p</i>-values for any set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values in this upper right triangle gives an indication of the power of the method.</p

Level of diversity and differentiation for NRY markers and mtDNA.

<p>We calculated the total allelic richness (<i>AR</i>) (over all populations) and the expected heterozygosity <i>H</i>_e<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Nei1" target="_blank">[55]</a> using Arlequin version 3.1 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Excoffier1" target="_blank">[56]</a>. Genetic differentiation among populations was measured both per locus and overall loci, using Weir and Cockerham's <i>F</i>_ST estimator <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Weir1" target="_blank">[57]</a>, as calculated in Genepop 4.0 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Rousset2" target="_blank">[58]</a>. We calculated the total number of polymorphic sites, the unbiased estimate of expected heterozygosity <i>H</i>_e<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Nei1" target="_blank">[55]</a>, and <i>F</i>_ST using Arlequin version 3.1 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000200#pgen.1000200-Excoffier1" target="_blank">[56]</a>.</p

Diagram representing the relative values of expected genetic differentiation for autosomal markers and for X-linked markers .

<p>In the red upper right triangle, the <i>F</i>_ST estimates for autosomal markers are higher than for X-linked markers. In this case, <i>N</i>_f/<i>N</i> is necessarily larger than 0.5. In the blue region of the figure, the <i>F</i>_ST estimates for autosomal markers are lower than for X-linked markers. The white plain line, at which , represents the set of (<i>N</i>_f/<i>N</i>, <i>m</i>_f/<i>m</i>) values where the autosomal and X-linked <i>F</i>_ST estimates are equal. In this case , if <i>N</i>_f = <i>N</i>_m, then the lower effective size of X-linked markers (which would be three-quarters that of autosomal markers) can only be balanced by a complete female-bias in dispersal (<i>m</i>_f/<i>m</i> = 1). Conversely, if <i>m</i>_f = <i>m</i>_m, the large female fraction of effective numbers compensates exactly the low effective size of X-linked markers only for <i>N</i>_f = 7<i>N</i>_m. Last, if <i>m</i>_f = <i>m</i>_m/2, then the autosomal and X-linked <i>F</i>_ST estimates can only be equal as the number of males tends towards zero.</p