Middle-Eastern genomes fill historical gaps

Despite being the cradle of agriculture, the birthplace of urbanisation and the land bridge that brought early hominins out of Africa, the Middle East as a region has flown relatively under the radar when it comes to genetic research. Now, a new study from the University of Birmingham and the Wellcome Sanger Institute, UK, has sequenced 137 full genomes from eight Middle-Eastern populations to reveal fascinating insights about human history.

“The Middle East is an important region to understand human history, migrations and evolution: it is where modern humans first expanded out of Africa, where hunter-gatherers first settled and transitioned into farmers, where the first writing systems developed, and where the first major known civilisations emerged,” says co-author Mohamed Almarri of the Wellcome Sanger Institute. With this in mind, many of our modern languages, cultures and behaviours can trace their roots to the region.

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The team, led by Almarri and Marc Haber of the University of Birmingham, were able to reconstruct the genomic history of the region with unprecedented precision, noting that many of their findings vindicate theories in the fields of archaeology and linguistics.

The key findings included the identification of 4.8 million new gene variants that are specific to the Middle East, and that were not identified in the Human Genome Diversity Project. The authors say these genes could provide clues about population health specific to the region.

“These are variants that were not previously discovered in other populations,” Haber says. “Hundreds of thousands of these are common in the region, and any of them could hold medical relevance.”

Bastien Llamas, an expert in population genomics and ancient DNA at the University of Adelaide (who was not involved in the study), says expanding our knowledge of the human genome to cover these blind spots will confer many potential benefits.

“Downstream benefits include addressing health issues specific to these populations that are under-represented in global reference databases, but also improving our understanding of disease molecular mechanisms – and this could be relevant for all humans.”

Another finding was evidence of a population bloom coterminous with the development of agriculture in the Levant region during the transition to the Neolithic some 8,000-10,000 years ago, supporting the long-held belief among archaeologists that farming – and the sedentary lifestyle it afforded – would’ve boosted the region’s population. Meanwhile, the genomes showed evidence some 6,000 years ago of a massive population crash in Arabia, around the time the once-verdant region experienced a dramatic drying event.

Shining light on the field of linguistics, the study also found that population movement in the Bronze Age may have spread the Semitic languages (these form the basis for today’s Arabic, Hebrew and Aramaic) out from the Levant into Arabia and East Asia.

Another key finding sheds light on the development of disease susceptibility, with the research showing an increase in the frequency of variants associated with type 2 diabetes in some Middle-Eastern populations over the past 2,000 years, showing that variants that may once have been evolutionarily beneficial can end up coding for disease.

“In this case, it looks like some genetic variants that are associated with diabetes in present-day Emirati populations were at high frequency in the population 2,000 years ago,” says Llamas. “It is entirely possible that these variants were positively selected to survive the arid environment and the nomadic herder lifestyle of the ancestors of Emirati people.”

The research opens a valuable window into the genomics of a population whose history is inextricably linked to much of the rest of the world.

“Our study fills a major gap in international genomic projects by cataloguing genetic variation in the Middle East,” says Chris Tyler-Smith of the Wellcome Sanger Institute. “The millions of new variants we found in our study will improve future medical association studies in the region. Our results explain how the genetics of Middle Easterners formed over time, providing new insights, which complement knowledge from archaeology, anthropology and linguistics.”