View Full Version : X-chromosome lineages and the settlement of the Americas

08-16-2012, 09:28 PM
Stephane Bourgeois et al. 2009 (limited access): http://onlinelibrary.wiley.com/doi/10.1002/ajpa.21084/abstract

Abstract (emphasis mine):

Most genetic studies on the origins of Native Americans have examined data from mtDNA and Y-chromosome DNA. To complement these studies and to broaden our understanding of the origin of Native American populations, we present an analysis of 1,873 X-chromosomes representing Native American (n = 438) and other continental populations (n = 1,435). We genotyped 36 polymorphic sites, forming an informative haplotype within an 8-kb DNA segment spanning exon 44 of the dystrophin gene. The data reveal continuity from a common Eurasian ancestry between Europeans, Siberians, and Native Americans. However, the loss of two haplotypes frequent in Eurasia (18.8 and 7%) and the rise in frequency of a third haplotype rare elsewhere, indicate a major population bottleneck in the peopling of the Americas. Although genetic drift appears to have played a greater role in the genetic differentiation of Native Americans than in the latitudinally distributed Eurasians, we also observe a signal of a differentiated ancestry of southern and northern populations that cannot be simply explained by the serial southward dilution of genetic diversity. It is possible that the distribution of X-chromosome lineages reflects the genetic structure of the population of Beringia, itself issued from founder effects and a source of subsequent southern colonization(s).

Selected excerpts:

In the last few decades, molecular biology and genetics have joined archaeology, anthropology, and linguistics in the quest for the understanding of the origins of Native Americans and the peopling of the Americas. Although it is generally accepted that the source of Native American migrations lies somewhere in North Eastern Asia and that the Bering Strait was the gateway to the Americas, there is no consensus as to the number and timing of the migrations, the number of migrants, and the routes they took.

The debate has principally been driven by studies of mtDNA and Y-chromosome diversity. Studies of the maternal lineages described five founding mtDNA haplogroups in the Native American population (Torroni et al., 1992, 1993; Brown et al., 1998), presently referred to as A2, B2, C1, D1, and X2a, respectively. All five mtDNA haplotypes were identified in ancient pre-Columbian Native American remains (Stone and Stoneking, 1998; Malhi et al., 2002; Jones, 2003). Recent mtDNA analyses suggest that ancestors of Native Americans paused when they reached Beringia, which served as a glacial refugium during last glacial maximum (LGM). At the end of LGM, the coastal route was presumably used to reach southern South America around 14,500 years ago, and this initial migration seems to have involved all five of the main mtDNA haplogroups (Tamm et al., 2007; Achilli et al., 2008; Fagundes et al., 2008). Amerindian Y-chromosome lineages consist of two major haplogroups, Q and C, also found among Asian populations. In the Americas, haplogroup Q is spread from north to south, while haplogroup C is restricted to the north and is especially frequent among NaDene speakers (Bortolini et al., 2003; Zegura et al., 2004; Malhi et al., 2008).

Until recently, data from other genetic systems were patchy with different markers studied in different population groups (Salzano, 2002). A recent study by Mateus Pereira et al. (2005) analyzed polymorphic L1 and Alu insertions in 11 Native American populations. They showed a strong affinity of Native Americans with East Asians and their clear discrimination from Europeans and Africans, and suggested that South-American diversity may have been caused by a major population bottleneck and genetic drift. Wang et al. (2007) studied variations in 29 Native American populations by genotyping 678 microsatellites from throughout the genome. They observed a decrease in genetic diversity in terms of geographic distance from the Bering Strait and from west to east in South America. Their results suggested that coastal routes played an important role in the peopling of the Americas, and that most Native American genetic ancestry could be derived assuming a single wave of migration. Interestingly, using an approximate Bayesian computation framework and coalescence-based simulations, Ray et al. (submitted) reanalyzed the same data to evaluate statistically the relative probability of alternative migration scenarios. They found that a model in which an initial migration wave is followed by recurrent gene flow between Asia and America provides by far the best fit to levels of genetic diversity observed across the American continent. Apparently, a strong signal of a single migration wave is not inconsistent with subsequent gene flow (Tamm et al., 2007). Although these studies analyzed collections of markers from all over the genome, less attention has been given to individual lineages of single DNA segments with correlated genealogies.

Studies focusing on a single locus may reveal specific aspects of the genetic past of studied populations that might be lost, less clear, or ‘‘invisible’’ in global analysis of many markers taken from throughout the genome. mtDNA and Y-chromosomes are effectively single loci and capture only partially the history of the population. Our study of nuclear DNA segments both complements analyses and challenges these studies.

We focus on the genetic lineages of an 8-kb DNA segment around exon 44, called dys44, in the middle of a very large dystrophin gene on Xp21. Its mostly intronic sequence can be expected to evolve neutrally (Nachman and Crowell, 2000). Because of the location in a highly recombining region, far from other genes and other dystrophin exons, we can also assume that its evolution has not been affected by selection acting on neighboring loci. X-chromosome facilitates work with extended haplotypes directly obtained in males. Because of its reduced sensitivity to genetic drift, the X-chromosome covers genetic lineages with greater historical depth than mtDNA or Y-chromosome data (Schaffner, 2004). X-linked markers have additional advantage to be less sensitive to the genetic admixture than the autosomal markers when admixture is mostly male-driven. Dys44 was investigated earlier in a number of human populations from different continents (Zietkiewicz et al., 1997, 1998, 2003; Xiao et al., 2004; Lovell et al., 2005). This study adds new information and further develops our understanding of the peopling of the Americas.

At the same time, our data reveal noticeable genetic differences between the south and the north, which cannot be solely ascribed to a more general effect of the loss of diversity by genetic drift during southward colonization movements (Torroni et al., 1993; Lorenz and Smith, 1997; Malhi et al., 2001; Ramachandran et al., 2005; Wang et al., 2007). We notice that the two lineages represented by haplotypes B003 and B006 that are responsible for the affinity between Native American, Siberian, and European samples observed in PCA and MDS plots (Fig. 3 and Supporting Information Fig. S4) are concentrated in northern populations (Figs. 1 and 2). Furthermore, northern populations are enriched in the variant B006-15, which predominates among contemporary Central Asians (Supporting Information Table S3), whose distribution seems to overlap with that of the Y-chromosome haplogroup C3b (Karafet et al., 1999; Bortolini et al., 2003; Zegura et al., 2004; Malhi et al., 2008). Recently, Hellenthal et al. (2008), based on the novel analysis of a set of data from 32 autosomal regions (Conrad et al., 2006), proposed that the sources of ancestry differed between Native South and North Americans. Accordingly, this could explain the relationship between distance from Siberia and greater genetic similarity to Siberians of northern populations in the data of Wang et al. (2007), where this similarity was originally attributed to serial dilution (Ramachandran et al., 2005). Although, as discussed earlier, our data are consistent with uneven ancestry of southern and northern populations as proposed by Hellenthal et al. (2008), they also point to a strong population bottleneck (Schroeder et al., 2007). A series of founder effects resulting in a genetically structured population of Beringia (Tamm et al., 2007; Achilli et al., 2008) as a source of subsequent southern colonization(s) could provide a plausible explanation for this apparent discrepancy. The analysis of X-linked lineages of Arctic populations could help testing this hypothesis. In this context, recent analysis of Ray et al. (submitted) using the data of Wang et al. (2007) is very revealing by suggesting a model in which an initial major migration wave is followed by recurrent gene flow between Asia and America. This could explain differences between southern and northern populations in spite of a strong signal of a bottleneck and single major migration wave observed with most of the genetic data. Another view on this issue was recently offered by Perego et al. (2009). They provided mtDNA evidence of two separate migrations from Beringia, which could explain the different distributions of haplogroup X2a in Northern and Southern Native American populations, thus further substantiating our conclusions based on X-chromosome