The 4,500-Year-Old Ethiopian Genome Unveil Extensive Eurasian Admixture; Surprise about Ancestry of Africans

DNA from a man who lived in Ethiopia about 4,500 years ago is prompting scientists to rethink the history of human migration in Africa. Until now, the conventional wisdom had been that the first groups of modern humans left Africa roughly 70,000 years ago, stopping in the Middle East en route to Europe, Asia, and beyond. Then about 3,000 years ago, a group of farmers from the Middle East and present-day Turkey came back to the Horn of Africa (probably bringing crops like wheat, barley, and lentils with them).

Population geneticists pieced this story together by comparing the DNA of distinct groups of people alive today. Since humans emerged in Africa, DNA from ancient Africa could provide a valuable genetic baseline that would make it easier for scientists to track genome changes over time. Unfortunately, such DNA has been hard to come by. DNA isn’t built to last for thousands of years. The samples of ancient DNA that have been sequenced to date were extracted from bodies in Europe and Asia that were naturally refrigerated in cooler climates.

That’s what makes the Ethiopian man so special. His body was found face-down in Mota cave, which is situated in the highlands in the southern part of the country. The cool, dry conditions in the cave preserved his DNA, and scientists extracted a sample from the petrous bone at the base of his skull. The resulting sequence is the first nuclear genome from an ancient African, according to a report published Thursday in the journal Science.

Radiocarbon dating revealed that the bone was 4,500 years old. That meant Mota (as the researchers called him) lived before Eurasians returned to the African continent. Consistent with that timeline, Mota did not have any of the genetic variants for light-colored eyes or skin that evolved in the populations that left Africa. Nor did he have variants that arose in Eurasian farmers that allowed them to digest milk as adults.

Mota did have three variants that are known to help modern-day Ethiopians live in high altitudes. (The present-day town of Mota lies more than 8,100 feet above sea level.) When the researchers compared Mota’s genome to those of contemporary humans, the closest match was with the Ari people of southern Ethiopia. With this information, the research team was able to investigate the mysterious group of Eurasians that came to Africa 3,000 years ago. They created a model that assumed the Ari genome was a mixture of DNA from Mota and an unknown population from west Eurasia. Then they “plugged in” DNA from several candidate populations to see if they could get a combination that looked like Ari DNA.

Two results stood out from the rest. One was for modern-day Sardinians, who are known to be the closest living relatives to the earliest farmers. The other was for members of the so-called LBK culture in Germany, early farmers who lived about 7,000 years ago. If the Eurasian settlers who arrived in Africa 3,000 years ago were indeed descendants of the LBK farmers, then the story of their migration through Africa needs to be revised, the researchers wrote.

The newly sequenced genome was sampled from the skull of an ancient human found in the Mota cave in the Ethiopian highlands. Photo by Kathryn and John Arthur/Cambridge

By comparing the LBK genome with DNA from Africans alive today, the scientists calculated that these ancient farmers may have made up 25% or more of the population in the Horn of Africa during the migration years. All of those migrants ultimately pushed farther into Africa than previously thought, they determined. African populations from the western and southern tips of the continent got at least 5% of their DNA from these Eurasian migrants, according to the study. Some groups from Ethiopia, Somalia, Djibouti, and Eritrea can trace more than 30% of their DNA to these migrants.

The ability to sequence ancient genomes has revolutionized our understanding of human evolution,” wrote the research team, which was led by Marcos Gallego Llorente of the University of Cambridge and Eppie Ruth Jones of Trinity College Dublin. They said they are eager to find “even older African genomes” that may make the story more complete.

Here is the full study:

Ancient African helps to explain the present

Tracing the migrations of anatomically modern humans has been complicated by human movements both out of and into Africa, especially in relatively recent history. Gallego Llorente et al. sequenced an Ethiopian individual, “Mota,” who lived approximately 4500 years ago, predating one such wave of individuals into Africa from Eurasia. The genetic information from Mota suggests that present-day Sardinians were the likely source of the Eurasian backflow. Furthermore, 4 to 7% of most African genomes, including Yoruba and Mbuti Pygmies, originated from this Eurasian gene flow.

Introduction

Characterizing genetic diversity in Africa is a crucial step for most analyses reconstructing the evolutionary history of anatomically modern humans. However, historic migrations from Eurasia into Africa have affected many contemporary populations, confounding inferences. Here, we present a 12.5× coverage ancient genome of an Ethiopian male (“Mota”) who lived approximately 4500 years ago. We use this genome to demonstrate that the Eurasian backflow into Africa came from a population closely related to Early Neolithic farmers, who had colonized Europe 4000 years earlier.

The ability to sequence ancient genomes has revolutionized our understanding of human evolution. However, genetic analyses of ancient material have focused on individuals from temperate and Arctic regions, where ancient DNA is preserved over longer time frames. Africa has so far failed to yield skeletal remains with much ancient DNA, with the exception of a few poorly preserved specimens from which only mitochondrial DNA could be extracted. This is particularly unfortunate, as African genetic diversity is crucial to most analyses reconstructing the evolutionary history of anatomically modern humans, by providing the baseline against which other events are defined. In the absence of ancient DNA, geneticists rely on contemporary African populations, but a number of historic events, in particular a genetic backflow from West Eurasia into Eastern Africa, act as confounding factors.

Here, we present an ancient human genome from Africa and use it to disentangle the effects of the recent population movement into Africa. By sampling the petrous bone, we sequenced the genome of a male from Mota Cave (herein referred to as “Mota”) in the southern Ethiopian highlands, with a mean coverage of 12.5×. Contamination was estimated to be between 0.29 and 1.26%. Mota’s remains were dated to ~4500 years ago [direct calibrated radiocarbon date] and thus predate both the Bantu expansion and, more importantly, the 3000-year-old West Eurasian backflow, which has left strong genetic signatures in the whole of Eastern and, to a lesser extent, Southern Africa.

We compared Mota to contemporary human populations. Both principal component analysis (PCA) (Fig. 1A) and outgroup f3 analysis using Ju|’hoansi (Khoisan) from Southern Africa as the outgroup (Fig. 1, B and C) place this ancient individual close to contemporary Ethiopian populations, and more specifically to the Ari, a group of Omotic speakers from southern Ethiopia, to the west of the highland region where Mota lived. Our ancient genome confirms the view that the divergence of this language family results from the relative isolation of its speakers (8), and indicates population continuity over the last ~4500 years in this region of Eastern Africa.

Fig. 1 Mota shows a very high degree of similarity with the highland Ethiopian Ari populations.(A) PCA showing Mota projected onto components loaded on contemporary African and Eurasian populations. The inset magnifies the PCA space occupied by Ethiopian and Eastern African populations. (B) Outgroup f3 quantifying the shared drift between Mota and contemporary African populations, using Ju|’hoansi (Khoisan) as an outgroup; bars represent SE. (C) Map showing the distribution of outgroup f3 values across the African continent. In (A) and (B), populations speaking Nilo-Saharan languages are marked with blue shades, Omotic speakers with red, Cushitic with orange, Semitic with yellow, and Bantu with green. Mota is denoted by a black symbol.

The age of Mota means that he should predate the West Eurasian backflow, which has been dated to ~3000 years ago. We formally tested this proposition by using an f4 ratio estimating the West Eurasian component, following the approach adopted by Pickrell et al. As expected, we failed to find any West Eurasian component in Mota (table S5), thus providing support for the previous dating of that event.

Given that Mota predates the backflow, we searched for its most likely source by modeling the Ari, the contemporary population closest to our ancient genome, as a mixture of Mota and another West Eurasian population. We investigated both contemporary sources (3) and other Eurasian ancient genomes. In this analysis, contemporary Sardinians and the early Neolithic LBK (Stuttgart) genome stand out. Previous analyses have shown Sardinians to be the closest modern representatives of early Neolithic farmers, implying that the backflow came from the same genetic source that fueled the Neolithic expansion into Europe from the Near East/Anatolia before recent historic events changed the genetic makeup of populations living in that region. An analysis with haplotype sharing also identified a connection between contemporary Ethiopians and Anatolia. Interestingly, archaeological evidence dates the arrival of Near Eastern domesticates (such as wheat, barley, and lentils) to the same time period (~3000 years ago), suggesting that the direct descendants of the farmers that earlier brought agriculture into Europe may have also played a role in the development of new forms of food production in the Horn of Africa.

Fig. 2 Quantifying the geographic extent and origin of the West Eurasian component in Africa.(A) Admixture f3 identifying likely sources of the West Eurasian component (lowest f3 values). Contemporary populations in blue, ancient genomes in red; bars represent SE. (B) Map showing the proportion of West Eurasian component, λMota,LBK, across the African continent.

Using Mota as an unadmixed African reference and the early farmer LBK as the source of the West Eurasian component, it is possible to reassess the magnitude and geographic extent of historical migrations, avoiding the complications of using admixed contemporary populations. We estimated a substantially higher Eurasian backflow admixture than previously detected, with an additional 4 to 7% of the genome of most African populations tracing back to a Eurasian source. Moreover, we detected a much broader geographical impact of the backflow, going all the way to West and Southern Africa. Even though the West Eurasian component in these regions is smaller than in Eastern Africa, it is still sizable, with Yoruba and Mbuti, who are often used as African reference populations, showing 7% and 6%, respectively, of their genomes to be of Eurasian origin (table S5).

Since Mota predates recent demographic events, his genome can act as an ideal African reference to understand episodes during the out-of-Africa expansion. We used him as the African reference to quantify Neandertal introgression in a number of contemporary genomes. Both Yoruba and Mbuti, which are routinely used as African references for this type of analysis, show a marginally closer affinity with Neandertal than Mota on the basis of D statistics, and an f4 ratio analysis detected a small Neandertal component in these genomes at around 0.2 to 0.7%—greater than previously suggested and consistent with our estimates of the magnitude of their Western Eurasian ancestry. Although the magnitude of Neandertal ancestry in these contemporary African populations is not enough to change conclusions qualitatively (estimates of Neandertal ancestry in French and Han only increased marginally when tested with Mota as a reference), it should be accounted for when looking for specific introgressed haplotypes or searching for unknown ancient hominins who might have hybridized with African populations.

We also investigated the Mota genome for a number of phenotypes of interest. As expected, Mota lacked any of the derived alleles found in Eurasian populations for eye and skin color, suggesting that he had brown eyes and dark skin. Mota lacked any of the currently known alleles that confer lactose tolerance, which may have implications concerning when pastoralism appeared in southwestern Ethiopia. In addition, Mota did possess all three selected alleles that recently have been shown to play a role in the adaptation to altitude in contemporary highland Ethiopian populations. The presence of these mutations supports our conclusion that Mota is the descendant of highland dwellers, who have lived in this environment long enough to accumulate adaptations to the altitude.

Until now, it has been necessary to use contemporary African populations as the baseline against which events during the worldwide expansion of anatomically modern humans are defined (16, 22–24). By obtaining an ancient whole-genome from this continent, we have shown that having an unadmixed reference that predates a large number of recent historical migrations can greatly improve our inference. This result stresses the importance of obtaining unadmixed baseline data to reconstruct demographic events, and the limitations of analyses that are solely based on contemporary populations. Even older African genomes will thus be needed to investigate key demographic events that predate Mota, such as earlier instances of backflows into Africa.

M. GALLEGO LLORENTEE. R. JONESA. ERIKSSONV. SISKAK. W. ARTHURJ. W. ARTHURM. C. CURTISJ. T. STOCKM. COLTORTI[…]A. MANICA +10 authors Authors Info & Affiliations

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