Genomic Data Reveal a Complex Making of Humans

Figure 3
PC analysis performed using haplogroup frequencies in the populations of this study. Gr, Greeks; Mac-Gr, Macedonian Greeks; Alb-A, Albanians; Alb-F, Albanians from FYROM; Sr-B, Bosnia-Serbs; Bs-B, Bosniacs; Cr-B, Bosnia-Croats; Cr-O, Croats from Osijek; Cr-H, Croats of Croatia; Slo, Slovenians; NE-I, northeast Italians; Hun, Hungarians; Cz, Czechs; Pl, Poles; Uk, Ukrainians; Geo, Georgians; Bk, Balkarians. Thirty-four percent of the total variance is represented. Insert illustrates the contribution of each haplogroup.

The PC analysis, from the perspective of population Hg frequencies (Figure 3), reveals a tight cluster of populations not comprising southern Balkan and Caucasian groups. Common to this cluster are lower frequencies of Hgs, G-M201 and J-M410, and higher frequencies of Hgs, I-M423, E-V13 and J-M241. Whereas the first two are primarily Middle Eastern Hgs and have been shown to be associated with the early Neolithic colonization of Crete,38, 46 Italy,47, 48 and southern Caucasus, I-M423, E-V13 and J-M241, in spite of parallel Balkan patterns of distribution, have clearly different origins.30, 31, 38 Their comparison can therefore provide insights into the complex interaction between the European Mesolithic foragers and the Middle Eastern Neolithic farmers during the transition to farming society in the Balkans. These Hgs, although characterized by different distribution patterns of frequency and variance (Figure 4), display networks of microsatellite haplotypic variation (Supplementary Figures S1–S3), all consistent with a Balkan expansion.

Various episodes of population movement have affected southeast Europe, and the role of the Balkans as a long-standing gateway to Europe from the Near East is illustrated by the phylogenetic unification of Hgs I and J by the basal M429 mutation.31 This evidence of common ancestry suggests that ancestral IJ-M429* Y chromosomes probably entered Europe through the Balkan route sometime before the Last Glacial Maximum. They subsequently evolved into Hg J in the Middle East and Hg I in Europe in a typical disjunctive phylogeographic pattern. Such a geographic corridor is likely to have experienced additional subsequent gene flows, including the migration of agricultural colonists from the Middle East. Pottery is a useful proxy for the spread of farming both spatially and temporally. The first appearance of pottery in the Adriatic region was in Corfu at 6500 BC and reached the northern most Adriatic ~1000 years later.21 Its dispersal provides a comparative template for spatial and temporal patterns of Y chromosome Hg diversity observed in this area.



Figure 4
Frequency (left) and variance (right) distributions of the main Y-chromosome haplogroups, I-M423, E-V13 and J-M241, observed in this survey. Frequency data are reported in Figure 2, variance data are relative to the examined microsatellite reported in the Supplementary Table S2. We acknowledge that interpolated spatial frequency surfaces should be viewed with caution because of sample size.41 • Data from this study. Frequency and variance values were assigned to sample-collection places (dots). Population samples (geographically close) with less than five observations were pooled and the corresponding variance assigned to a middle position of the pooled sample locations. +Data from the literature.

Hg J is most common (~50%) in the Middle East and Anatolia,27, 29, 47 with a spread zone spanning from northwest Africa to India.12, 55 It has been related to different Middle Eastern migrations.12, 56 In addition to Hg J-M410, Hg G-P15 chromosomes, which are also common in Anatolia,29 have been implicated in the colonization and subsequent expansion of early farmers in Crete, the Aegean and Italy.38, 46, 47, 48 Earlier studies have concluded that the J-M410 sub-clades, J-DYS445-6 and J-M67, are linked to the spread of farming in the Mediterranean Basin,38, 47 with a likely origin in Anatolia.29 Interestingly, J-DYS445-6 and J-M92 (a sub-lineage of M67), both have expansion times between 7000 and 8000 years ago (Table 1), consistent with the dating of the arrival of the first farmers to the Balkans. The first detection of milk residue in ceramic pottery occurs in sites from northwest Anatolia 7000–8500 years ago,58 an age that approximates the Hg-expansion times.

As reported earlier,28 both J-M12 and E-V13 radiation patterns overlap geographically in the Balkans (Figure 4). Although J-M12 chromosomes were not genotyped for M241 by Cruciani et al,28 the low YSTR diversity observed suggests that these are predominantly M241 derivatives. The difference between E-V13 and J-M241 (Table 1) indicates that both E-V13 frequency and haplotype diversity would have been greater than J-M241 components just before the episode of population growth. This also is the case when the dating is carried out by disregarding the mutational steps connecting the three haplotypes that, including Turkish samples (Supplementary Figure S2), can be considered as founders.62 Whether or not E-V13 and J-M241 participated in the same demography remains uncertain.

The presence of E-M78* Y chromosomes in the Balkans (two Albanians), previously described virtually only in northeast Africa, upper Nile,28, 63 gives rise to the question of what the original source of the E-M78 may have been. Correlations between human-occupation sites and radiocarbon-dated climatic fluctuations in the eastern Sahara and Nile Valley during the Holocene64 provide a framework for interpreting the main southeast European centric distribution of E-V13. A recent archaeological study reveals that during a desiccation period in North Africa, while the eastern Sahara was depopulated, a refugium existed on the border of present-day Sudan and Egypt, near Lake Nubia, until the onset of a humid phase around 8500 BC (radiocarbon-calibrated date). The rapid arrival of wet conditions during this Early Holocene period provided an impetus for population movement into habitat that was quickly settled afterwards.64 Hg E-M78* representatives, although rare overall, still occur in Egypt, which is a hub for the distribution of the various geographically localized M78-related sub-clades.28 The northward-moving rainfall belts during this period could have also spurred a rapid migration of Mesolithic foragers northwards in Africa, the Levant and ultimately onwards to Asia Minor and Europe, where they each eventually differentiated into their regionally distinctive branches.

Differently from the earlier discussed Hgs, I-M423 represents the southeast European autochthonous clade of I-P37.2. Its distribution reaches Anatolia, where, however, it is only sporadically observed (2.6%, updated from Rootsi et al23). Also, virtually, all the I-P37.2* paragroup members identified in this survey harbouring the peculiar DYS388-15 trinucleotide repeat motif (not observed in any other Hg I clade) likely represent a new rare P37.2 sub-clade. Their distribution (Supplementary Table S1) and the associated YSTR variation age of ~4000 years (Table 1) suggest that they expanded demographically, perhaps from central European regions during the Bronze Age. In this scenario, the only I-P37.2* chromosome observed in Albania, not characterized by the unusual DYS388-15 repeat motif marker, could either represent the consequence of a reversion event back to the ancestral allele or be a rare representative of the ancestral P37.2 state.

European Journal of Human Genetics (2009) 17, 820–830; doi:10.1038/ejhg.2008.249; published online 24 December 2008

In population genetics, effective population size is not a direct measure of the total number of people that lived at a given time. It is rather a measure of genetic diversity. Experts trace an individual’s DNA back through history, looking for differences in the DNA sequences between the two copies of his or her genome. Essentially, they estimate how many generations of relatedness separate the maternal copy of a gene from the paternal copy. If a population is small, they can expect to reach the common ancestor relatively quickly; if it is larger, it takes longer. “It’s amazing that you can get this much information out of a single individual,” Rogers said.

Scientists’ longstanding impression has been that Neanderthals had low levels of genetic diversity. In African individuals today, approximately 11 of every 10,000 nucleotides are heterozygous, meaning they differ between two copies of a chromosome. In non-African individuals, only eight of every 10,000 sites are. That figure seemed to drop to a mere two of 10,000 for Neanderthals, as well as for their sister species, the Denisovans, which science only identified in the past decade. “Population genetics theory tells us that means a small population size” for those archaic humans, said Montgomery Slatkin, a biologist at the University of California, Berkeley, who was not convinced of Rogers’ results. That might mean 2,000 to 3,000 individuals — certainly not the far larger population inferred from the density of stone tools and fossils the Neanderthals left behind.



But genetic evidence is exactly what Rogers and his colleagues have now cited to support their claim that the Neanderthals effectively numbered in the tens of thousands. They made their argument in a study published last month in the Proceedings of the National Academy of Sciences.

The key to this new result lies in the researchers’ assumption that Neanderthals had a much more diverse gene pool, but that it was divided into small, isolated, inbred groups of genetically similar individuals. This kind of fragmentation would have skewed the earlier genetic results: Estimates like that 2-in-10,000 number described the local populations and their regional histories but missed the big picture.




Rogers looked to make up for this shortcoming by adapting and extending a model of population mixing that other researchers had used. Instead of analyzing a single individual’s genome, he and his team compared genetic variants shared by modern Africans, modern Eurasians, Neanderthals and Denisovans. An earlier version of this model had been designed to estimate how much modern humans and Neanderthals interbred. Rogers’ main innovation was to add the Denisovans into the mix and significantly increase the number of ways different populations could combine and mingle. Doing so allowed him to ask questions that extended far beyond interbreeding to population size and other concerns.

The increase in genetic diversity that Rogers and his colleagues found corresponds to a roughly tenfold increase in effective population size. Although there is no way of knowing how many more Neanderthal individuals that number may represent, it could go a long way toward meeting the estimates from the fossil data.

Approximately 750,000 years ago, according to Rogers, the forerunners of Neanderthals and Denisovans left the ancestors of modern humans behind in Africa to make their way across Eurasia’s expansive territory. Once on their own, something nearly wiped them out entirely; the genetic data shows the population passed through a severe bottleneck, never observed in previous studies. But whatever caused that brush with disaster, the archaic humans bounced back from it, and just a few thousand years later — by 744,000 years ago — they separated into two separate lineages, the Neanderthals and the Denisovans. The former then split further into the smaller regional groups that so fascinated Rogers.



The dating of that schism between the Neanderthals and the Denisovans is surprising because previous research had pegged it as much more recent: a 2016 study, for instance, set it at only 450,000 years ago. An earlier separation means we should expect to find many more fossils of both eventually. It also changes the interpretation of some fossils that have been found. Take the large-brained hominid bones belonging to a species called Homo heidelbergensis, which lived in Europe and Asia around 600,000 years ago. Paleoanthropologists have disagreed about how they relate to other human groups, some positing they were ancestors of both modern humans and Neanderthals, others that they were a nonancestral species replaced by the Neanderthals, who spread across Europe.

Rogers’ findings imply that the H. heidelbergensis had to have been an early Neanderthal. “The separation time we estimate is so early that a European hominid from 600,000 years ago pretty much has to be a Neanderthal,” he said, “at least genetically, even if they didn’t look entirely like Neanderthals yet.”