A summary of interesting recent genetics papers.

I'm taking a break from my Summer break to post a few interesting papers that have come out within the past couple of months.

(1) Inferring Demographic History from a Spectrum of Shared Haplotype Lengths (Open Access)

This paper supports such a notion of continuous gene-flow between Africans and non-Africans since the major Out of Africa event that was precursor to the populating of all continents outside of Africa.

To be sure, such a notion is not new but has been highlighted before by methods used by authors such as Li and Durbin (2011) for instance. Such a notion, is also sufficient to explain the intermediate genetic nature of West Eurasians, I.e between Africans and East Asian/Native Americans, that I have blogged about and demonstrated using ADMIXTURE in the past.

A few quotes from the paper:

"In this paper, we study the length distribution of tracts of identity by state (IBS), which are the gaps between pairwise differences in an alignment of two DNA sequences. These tract lengths contain information about the amount of genetic diversity that existed at various times in the history of a species and can therefore be used to estimate past population sizes. IBS tracts shared between DNA sequences from different populations also contain information about population divergence and past gene flow. By looking at IBS tracts shared within Africans and Europeans, as well as between the two groups, we infer that the two groups diverged in a complex way over more than 40,000 years, exchanging DNA as recently as 12,000 years ago." 

"To illustrate the power of our method, we use it to infer a joint history of Europeans and Africans from the high coverage 1000 Genomes trio parents. Previous analyses agree that Europeans experienced an out-of-Africa bottleneck and recent population growth, but other aspects of the divergence are contested [47]. In one analysis, Li and Durbin separately estimate population histories of Europeans, Asians, and Africans and observe that the African and non-African histories begin to look different from each other about 100,000–120,000 years ago; at the same time, they argue that substantial migration between Africa and Eurasia occurred as recently as 20,000 years ago and that the out-of-Africa bottleneck occurred near the end of the migration period, about 20,000–40,000 years ago. In contrast, Gronau, et al. use a likelihood analysis of many short loci to infer a Eurasian-African split that is recent enough (50 kya) to coincide with the start of the out of Africa bottleneck, detecting no evidence of recent gene flow between Africans and non-Africans [14]. The older Schaffner, et al. demographic model contains no recent European-African gene flow either [48], but Gutenkunst,et al. and Gravel, et al. use SFS data to infer divergence times and gene flow levels that are intermediate between these two extremes [22], [49]. We aim to contribute to this discourse by using IBS tract lengths to study the same class of complex demographic models employed by Gutenkunst, et al. and Gronau, et al., models that have only been previously used to study allele frequencies and short haplotypes that are assumed not to recombine. Our method is the first to use these models in conjunction with haplotype-sharing information similar to what is used by the PSMC and other coalescent HMMs, fitting complex, high-resolution demographic models to an equally high-resolution summary of genetic data."

"We estimate that the European-African divergence occurred 55 kya and that gene flow continued until 13 kya. About 5.8% of European genetic material is derived from a ghost population that diverged 420 kya from the ancestors of modern humans. The out-of-Africa bottleneck period, where the European effective population size is only 1,530, lasts until 5.9 kya."

"Our inferred human history mirrors several controversial features of the history inferred by Li and Durbin from whole genome sequence data: a post-divergence African population size reduction, a sustained period of gene flow between Europeans and Yorubans, and a “bump” period when the ancestral human population size increased and then decreased again. Unlike Li and Durbin, we do not infer that either population increased in size between 30 and 100 kya. Li and Durbin postulate that this size increase might reflect admixture between the two populations rather than a true increase in effective population size; since our method is able to model this gene flow directly, it makes sense that no size increase is necessary to fit the data. In contrast, it is possible that the size increase we infer between 240 kya and 480 kya is a signature of gene flow among ancestral hominids."

"Our estimated divergence time of 55 kya is very close to estimates published by Gravel, et al.and Gronau, et al., who use very different methods but similar estimated mutation rates to the  per site per generation that we use in this paper. However, recent studies of de novo mutation in trios have shown that the mutation rate may be closer to  per site per generation [51], [55], [56]. We would estimate older divergence and gene flow times (perhaps  times older) if we used the lower, more recently estimated mutation rate. This is because the lengths of the longest IBS tracts shared between populations should be approximately exponentially distributed with decay rate ."

(2) Genetic and archaeological perspectives on the initial modern human colonization of southern Asia (Closed Access)

This paper discusses some points, rather the lack of evidence, that makes a pre-toba migration of modern humans outside of Africa almost impossible to reconcile with currently available evidence.

A few quotes from the paper:

"There are currently two sharply conflicting models for the earliest modern human colonization of South Asia, with radically different implications for the interpretation of the associated genetic and archaeological evidence (Fig. 1). The first is that modern humans arrived ∼50–60 ka, as part of a generalized Eurasian dispersal of anatomically modern humans, which spread (initially as a very small group) from a region of eastern Africa across the mouth of the Red Sea and expanded rapidly around the coastlines of southern and Southeast Asia, to reach Australia by ∼45–50 ka (7–10, 14–18) (Fig. 2). The second, more recently proposed view, is that there was a much earlier dispersal of modern humans from Africa sometime before 74 ka (and conceivably as early as 120–130ka), reaching southern Asia before the time of the volcanic “supereruption” of Mount Toba in Sumatra (the largest volcanic eruption of the past 2 million y) at ∼74 ka (1–6)."

"We find no evidence, either genetic or archaeological, for a very early modern human colonization of South Asia, before the Toba eruption. All of the available evidence supports a much later colonization beginning ∼50–55 ka, carrying mitochondrial L3 and Y chromosome C, D, and F lineages from eastern Africa, along with the Howiesons Poort-like microlithic technologies (see above and Genetics and Archaeology). We see no reason to believe that the initial modern human colonization of South and Southeast Asia was distinct from the process that is now well documented for effectively all of the other regions of Eurasia from ∼60 ka onward, even if the technological associations of these expanding populations differed (most probably for environmental reasons) between the eastern and northwestern ranges of the geographical dispersal routes."

"The archaeological evidence initially advanced to support an earlier (pre-Toba) dispersal of African-derived populations to southern Asia has since been withdrawn by the author responsible for the original lithic analyses, who now suggests that they are most likely “the work of an unidentified population of archaic people” (ref. 11, p. 26). Meanwhile, the genetic evidence outlined earlier indicates that any populations dispersing from Africa before 74 ka would predate the emergence of the mtDNA L3 haplogroup, the source for all known, extant maternal lineages in Eurasia (8, 28) (Fig. 5). The size of the mtDNA database is very substantial: currently there are almost 13,000 complete non-African mtDNA genomes available, not one of which is pre-L3."

(3) An experimental computer-generated Y-chromosomal phylogeny, leveraging public Geno 2.0 results and the current ISOGG tree

This paper, written by a geneaolgoical community member, has made an impressive effort at creating and automating a comprehensive method to pylogenetically classify Geno 2.0 YDNA SNPs. Details of the algorithm are not available:

"To illustrate this, the author has used this Y-tree clade predictor (using the latest ISOGG tree as a basis for comparison) to classify over 1650 sets of publicly accessible Geno 2.0 Y-SNP calls. This information was then used as an input into another algorithm designed by the author – an algorithm developed to automate the construction of a phylogenetic Y-tree, while overcoming the challenges identified above. The technical details of this process will remain proprietary for the time being."