New findings in Middle Eastern genomics show huge promise towards further understanding the human genome.
The Middle East is a largely underrepresented region in the present genomic landscape. It contains some of the earliest evidence of modern humans outside of Africa, and is undoubtedly important in understanding human evolution, history, and migration. It is thought that climate fluctuations from humid to arid periods caused mass migrations, resulting in population adaptations to the environment. On top of this, high past consanguinity rates have resulted in present recessive gene-disease susceptibility, making the Middle East a unique and useful tool in the study of human genomics.
Genome sequencing the Middle East
A recent study investigated Middle Eastern ancestry and population characteristics. The primary aim was to create a catalogue of genetic variation in understudied regions, with hopes of assisting future medical studies. In addition to this, population structure, demographic and selective histories were also investigated.
Scientists carried out linked-read sequencing to generate 137 high-coverage physically phased genome sequences across eight current Middle Eastern populations. This type of sequencing involves the estimation of haplotypes from extensive genomic data, enabling allele imputation and comparisons against large reference databases. A total of 23.1 million single-nucleotide variants were identified and compared to variants in the ‘Human Genome Diversity Project’. This is a large dataset cataloguing genetic variation across coding and non-coding regions of the human genome.
Furthermore, searching genome-wide genealogies enabled the detection of relatively weak variants, as well as lineages carrying mutations that had spread unusually quickly. Select variants could then be linked back to selective pressure and major historic events, such as climate aridification and migration patterns of Middle Eastern populations. Additionally, the application of ancestral recombination graphs to reconstruct the evolutionary history of variants was found to be a powerful method in studying natural selection.
Middle Eastern Genomic discoveries
The results identified multiple variants showing evidence of selection, including polygenic selection linking to the population bottlenecks around climate aridification periods. They highlighted the influence of polygenic selection in increasing the frequency of variants which may have been beneficial many centuries ago, but are presently associated with diseases such as type II diabetes. Furthermore, ancestral investigations revealed that Middle Eastern populations had no ancestry from early out-of-Africa expansion. Insteatd, the data suggested that Arabians have elevated Basal Eurasian ancestry depleting their Neanderthalic ancestry. Furthermore, small past population sizes in the Middle East (also believed to have been influenced by climate) have likely contributed to homozygous loss-of-function mutation susceptibility today.
Advancing Middle Eastern studies
The exploration of Middle Eastern genomes offers huge promise in advancing human genetics research, but are still greatly limited by lack of comprehensive education and cultural stigmas. Nevertheless, it is encouraging that national genome projects will hopefully expand to several overlooked countries and lead to the share of broader, more representative data, in turn contributing to enhanced whole human genome studies.
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