More African Genomes are Being Sequenced to Increase the Diversity of Genomic Data

About 30 million or so people have had their DNA sequenced in the 20 years after the first human genome was decoded. Yet, only of these genomes are of people of African ancestry.

Over 30 million additional people have had their DNA sequenced in the 20 years since the first human genome was completed. Nonetheless, less than 2% of these genomes are from those of African ancestry. This exposes a huge vacuum in our understanding of human genetic variation and evolution, and it also suggests that there is room for far greater use of DNA knowledge in the treatment of disease.

A recent genome analysis of native African populations begins to fill in some of those gaps. An international team sequenced and studied the genomes of 180 individuals from 12 geographically, linguistically, culturally, and ethnically diverse communities throughout the continent for a Cell¹ article.

There is a lot of diversity in Africa, much of it probably functionally significant. It's sort of a treasure trove of variants that scientists can look at in the future. Why it hasn’t yet been studied in detail is multifactorial.

Firstly, given how quickly DNA from ancient samples degrades in many African regions due to the heat and humidity, it’s one significant reason academics know less about the genetics of historic human populations in Africa than they do in other regions of the world. But that doesn’t excuse really why modern populations haven’t been studied. Therefore, genome sequencing of contemporary individuals is the particular focus of this study… especially isolated groups.

The genomes of Africans have been sequenced before, but this is the first study to specifically concentrate on those who reside in some of the most isolated and rural areas. It took many years of research, teaming with African collaborators, just to even gather the samples and to secure all the right permits and to do this in an ethical manner.

The 12 populations studied either still engage in traditional undertakings including farming, herding animals, and hunting and gathering today or in the past. The study has started to reconstruct how African peoples moved and interbred over generations and determine when they last had a common ancestor by using models to analyze and compare shared patterns of variation within the DNA sequences from the various groups.

Earlier investigations had revealed only the San people (pictured) had descended from the most ancient humans. Recent genome sequencing indicated that actually both the San and a group of rainforest living hunter gatherers from central Africa were descended from the most ancient populations.

For example, one of the most intriguing discoveries was that two of the population groups, a group of hunter-gatherers from central Africa who lived in rain forests known as the Bantu and a group of southern Africans known as the San, both descended from the oldest populations and separated from one another and other known groups more than 200,000 years ago. Only the San were thought to be the descendants of the oldest people, according to earlier assessments.

Also, a previously undiscovered and now extinct branch of the human family may have once lived in Africa and mixed with other populations, according to the simulations. The Neanderthal and Denisovan genomes were introduced into contemporary humans through interbreeding outside of Africa. Africa might have seen the same thing take place. The trouble is we don't have ancient DNA from that time period.

The investigation also discovered genetic proof of local adaptability. DNA sequences, for instance, revealed enrichment for variations close to genes involved in kidney function and development in pastoral groups from East Africa as an adaptation to arid circumstances.

The report emphasizes the scientific necessity of sequencing the African population. The paucity of African DNA information in existing genome sequence studies means that major sources of variation are ignored, which can render study results, for example those focused on the genetic basis of disease, less relevant for persons of African ancestry.

This has been proved with the UK biobank project, where research suggest that statistical methods to correlate genes to illness risk function poorly among black British people of African descent. People of African ancestry, likely have genetic variation that is not well represented in the majority of genomes, which are primarily those of people with European heritage.

The authors are currently investigating potential clinical consequences of the DNA variation patterns they discovered in the African genomes for modern humans. These include genes that appear to affect heart development, bone growth, and skin color. Understanding how these genes are controlled could help them comprehend things like how the heart muscle usually develops and, in turn, why some people are more prone to cardiovascular illness.

The findings contribute to the understanding of historical and contemporary migratory patterns and offer genetic proof of environmental adaptability. Non-Africans are going to tend to have a subset of variety in Africa because of our human evolutionary past. Hence, by describing the diversity in Africa, we can all learn something and have an impact on populations around the world.

1. Fan, S., Spence, J. P., Feng, Y., Hansen, M. E. B., Terhorst, J., Beltrame, M. H., Ranciaro, A., Hirbo, J., Beggs, W., Thomas, N., Nyambo, T., Mpoloka, S. W., Mokone, G. G., Njamnshi, A., Folkunang, C., Meskel, D. W., Belay, G., Song, Y. S., & Tishkoff, S. A. (2023). Whole-genome sequencing reveals a complex African population demographic history and signatures of local adaptation. Cell, 186(5), 923-939.e14. https://doi.org/10.1016/j.cell.2023.01.042