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."

The Mother of Mothers !

It has been well known for about 20 years now that the mother of all Non-Africans, and indeed a lot of Africans, was an East African woman, in more recent nomenclature this woman has been called L3, so what do geneticists recently say about this woman, mother to greater than six and a half billion people on Earth, including many who still inhabit her original homeland?

The most recent study conducted to uncover the story behind L3 and her compatriots was one from the end of last year entitled “The Expansion of mtDNA Haplogroup L3 within and out of Africa”. 

This important study capped the timing of the out of Africa migrations, which all contemporary men and women outside of Africa are descended from, to no earlier than Seventy Thousand Years Ago.

The basis for this reasoning can be found in this paragraph from the text:

“The time window for the out-of-Africa migration on the basis of mtDNA lies between the emergence of haplogroup L3 in Eastern Africa and its derivative non-African haplogroups M and N, which most likely arose during the departure or outside Africa (Richards et al. 2006).”

Meaning, since all Non-Africans are descended from this woman, the timing of the out of Africa migration can not be any older than when she lived and can not be any younger than when here descendant daughters M and N lived, although there still remains a possibility that M and N emerged in Africa, albeit increasingly unlikely.

The expansion of L3 however has been linked in the past to not only the Out of Africa expansion but also Expansions within Africa, generally in association with two different episodes:

1. With the spread of Pastoralism in the Sahara of the early Holocene
2.  With the Bantu Expansion/s

To this end, the samples for this study were said to come from:

“We collected a total of 102 Sudanese, 77 Ethiopian (both emigrants in Dubai), and 148 Somali (refugees in Yemen) samples, belonging to unrelated individuals, who gave appropriate informed consent for their biological samples to be used for mtDNA characterization.”

Where a set of identified L3 lineages from above (plus other previous papers) were then selected for complete mtDNA sequencing:

“We selected for complete mtDNA sequencing a total of 21 Sudanese, 16 Ethiopian, and 20 Somali samples chosen from the sequences characterized in this work, and 11 from Chad and 2 from Soqotra belonging to haplogroup L3 from data sets published previously (Cerny´ et al. 2007; Cerny´, Pereira, et al. 2009).”

So what were the main results of the extensive statistical analysis done on this lineage?

A) Complete mtDNA phylogeny for Haplogroup L3:

 

Schematic tree of haplogroup L3. Age estimates are respectively rho estimates from the complete mtDNA genome (black font), rho estimates using the synonymous clock (gray font), and ML estimates using the complete mtDNA genome (black font underlined). Color scheme for each clade indicates the probable geographic origin. Haplogroups M and N are indicated and age estimates are according to Soares et al. (2009). MSA refers to Middle Stone Age and LSA to Late Stone Age.

B) Reaffirmation of what was known in the past with respect to the origins of L3:

“L3 most likely had an origin in Eastern Africa (Torroni et al. 2006). This is supported by the presence of all major branches, with L3a and L3h virtually specific to the region and L3eikx and the L3f haplogroups having a probable origin there as well, whereas for L3bcd, the region of origin is less clear and will be discussed in more detail below. The other two main branches of L3, M and N, exist only outside Africa, except for some back-migrations into Africa around 50–30 ka in the form of haplogroups U6 and M1 (Olivieri et al. 2006; Pereira et al. 2010) and some more recent intrusions (Cherni et al. 2009; Ottoni et al. 2010). Since there is strong evidence that the dispersal out of Africa was via the Horn, soon after L3 arose (Macaulay et al. 2005), the distribution of M and N also points to Eastern Africa as the center of gravity for L3.”

C) Temporal analysis of the sampled L3 lineages with origins bracketed within 60 – 70 thousand years ago:

 

"It seems likely that L3 dates somewhere between 60 and 70 ka, as the TMRCA estimates vary between 58.9 ka (using rho and the complete genome) and 70.2 (using ML), with the synonymous clock providing a value between the two (63.1 ka). We checked if the L3 tree rejected a strict molecular clock by running the ML analysis without stipulating a molecular clock and performing a likelihood ratio test that clearly did not reject the clock hypothesis (P 5 0.9899). These results led us to consider an age of 65 ka (varying between 60 and 70 ka in the 95% percentile) in the internal calibration of BEAST, as there was no other reliable calibration point we could use. The ages using the complete genome and the synonymous clock were 1.04 and 0.97 times the BEAST estimates, respectively, indicating that the BSPs were calculated using a similar rate to the other analyses, as we intended.”

D) Identification of 3 main episodes of population growth/expansion within Africa:

i) Approximately 40 thousand years ago corresponding with the emergence of the various intra-African subclades of L3.

ii) Around the Holocene, associated mainly with L3bd and L3e (Central Africa)

iii) The largest increase of the expansions detected around four thousand years ago and most pronounced in the Central African Bayesian Skyline Plots.

E) L3f and L3eikx both implied to have an origin in Eastern Africa. Where L3f was carried into the Sahel and Central Africa, with L3f3 specifically expanding into the Sahel 8 to 9 thousand years ago.

F) The most frequent clade of L3, i.e. L3e implied to have an origin in Central/Western Africa. With Eastern African L3e discounted as more recent introgression from there.

 

G) An ambiguous interpretation for the origin of L3bcd, a tentative east African origin is however suggested:

“L3bcd has three main subclades, with L3b and L3d tentatively united by a transition at control region position 16124 to form the putative subclade L3bd. The great age of L3bcd and its wide distribution across Africa makes phylogeographic inferences difficult. Furthermore, L3c is extremely rare: Only two samples have been detected so far, one in Eastern Africa and the other in the Near East. This might echo an early origin of L3bcd in Eastern Africa, before moving west, but its rarity makes this conclusion extremely tentative. In a scenario of an early origin of L3bcd in Eastern Africa, M and N would be the only subclades of L3 to have most likely originated outside of Eastern Africa (although an origin in Eastern Africa remains possible: Richards et al. 2006).

H) A virtual exclusion of a scenario in which the ancestors of contemporary people outside of Africa migrated out of Africa before the eruption of Toba.

I) And finally the most interesting part of this paper's conclusion, a unified demographic process that led to both the out-of-Africa and within Africa primary expansion of L3:

“Furthermore, since the age of the M and N Eurasian founders of ;50 to 65 ka (Soares et al. 2009) is close to the age of their ancestral L3 clade in Africa, the out of-Africa dispersal may have been of a piece with the initial diversification and expansion of L3, so that the L3 expansions in Eastern Africa and the exit of modern humans from Africa;60 ka were all part of a single demographic process.

It seems likely that the moister climate after;70 ka in Eastern Africa allowed dramatic human population growth (Scholz et al. 2007), perhaps associated with improved hunting, marine exploitation, exchange networks, and possibly even plant food management strategies as suggested by Mellars (2006). This generated the oldest major signal of expansion in the human mtDNA tree, the radiation of L3, leading rapidly to the spread of H. sapiens toward the rest of the world. It is worth stressing that this signal is not reflected in other mtDNA lineages at this time (Behar et al. 2008). Within Africa, the Pleistocene migrations detected in the L3 pool were responsible for the introduction of L3bd and L3e into Central Africa in the period between 60 and 35 ka (fig. 5A), but none reached Southern Africa at that time.”

Interestingly, the previous explanations that the Out of Africa expansion of modern humans being linked with behavioral modern thinking is largely dismissed by these authors for the sole explanation of Environmental factors, their main reasoning being that there is evidence for behavioral modernity of humans in Africa (Both in South and North Africa) long before their proposed timing of the OOA migrations.

“Thus, as suggested by Basell (2008), the demographic expansions that led to the first successful dispersal out of Africa seem better explained by the play of palaeoenvironmental forces than by recourse to the advantages of ‘‘modernity." 

More interesting figures from the paper:

“Frequency maps based on HVS-I data for haplogroups L3a, L3i, L3h, and L3x combined (A), L3f (B), L3e (C), L3b (D), and L3d (E).”

“Outline of the main dispersals detected in this work during the Pleistocene (A) and the Holocene (B).”

 ** Sketches on top of page depicting contemporary women that still live in the putative land of  L3's origin. Credit goes to Ethiopian Artist Adis Gebru and taken from this blog.