Study analyzes human genomes from the Middle East

Whole-genome sequencing activities across the globe have provided valuable insights into historical migrations, human diversity, and the relationships between people of different regions—however, researchers still do not have an entire picture as some regions and people remain understudied.

Genome Sequencing. Image Credit: Tartila/Shutterstock.com

Recent research serves to fill one of these biggest gaps by generating more than 100 high-coverage genome sequences from eight Middle Eastern populations employing linked-read sequencing. The research findings were published on August 4^th, 2021, in the Cell journal.

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 civilizations emerged. However, despite this importance, the region has been historically understudied in genomic studies.”

Mohamed Almarri, Wellcome Sanger Institute

In recent research, Almarri, Marc Haber (University of Birmingham, United Kingdom), and co-workers sequenced 137 whole genomes from eight Middle Eastern populations.

The scientists used a new sequencing technology called linked-read sequencing to generate the most comprehensive resource of human genetic variation in the Middle East. They could reconstruct the genomic history of the region with unmatched resolution.

They declare that some events recorded in the Middle Eastern genomes could be associated with what is known from archeology or linguistics, like the invention of agriculture and the spread of Semitic languages. However, other events could be explained only by analyzing the DNA of ancient and modern people who lived in the region.

Certain prominent findings of the research include:

• The identification of 4.8 million new gene variants that are specific to Middle Eastern populations that proves the basis for future research.
• Genetic variants that showcase evidence of selection—in other words, mutations that spread unusually rapidly—possibly due to adaptation to the changing lifestyle and environment
• In the Levant, where agriculture was first developed, populations accomplished a huge growth around the transition to agriculture that was not paralleled in Arabia
• Arabian populations suffered a severe population decrease around 6,000 years ago, which correlates with the climate change in Arabia, converting it from a green, wet region into the largest sand desert in the world today
• Middle Easterners are descendants of the same population that expanded out of Africa 50,000 to 60,000 years ago
• Arabian groups have notably lower Neanderthal ancestry when compared to other Eurasians, possibly due to excess basal Eurasian and African ancestry in Arabians that depletes their Neanderthal ancestry
• The movement of populations during the Bronze Age potentially resulted in the spread of the Semitic languages from the Levant to Arabia and East Africa.
• Higher frequency of variants linked with type 2 diabetes in some populations in the past 2,000 years suggests that variants that were beneficial in the past are associated with diseases today

“We found 4.8 million variants that were not previously discovered in other populations. Hundreds of thousands of these are common in the region, and any of them could hold medical relevance,” states Haber.

Our study fills a major gap in international genomic projects by cataloging genetic variation in the Middle East. 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 archeology, anthropology, and linguistics.”

Chris Tyler-Smith, Wellcome Sanger Institute

The scientists intend to follow up on variants that showcase evidence of selection. With the help of continued studies, they desire to further understand the biological effects of the newly found variants while refining the genetic history of the region.