Sudan lies at the crossroads of Africa and the Middle East. It has played a key role in human demographic movements, reflected in the diversity of its cultures and languages. Although much of the country is arid, the Nile River has long acted as a corridor for trade, facilitating human migration through the region for thousands of years.This makes Sudan a valuable place to study human genetic diversity and evolutionary history, which has important implications for understanding population-specific adaptation and health.The Copts are a population that migrated from Egypt from the 7th century and mixed with populations in neighbouring regions, but also remained somewhat isolated. Copts are historically distinguished by their Christian faith and their language. In Sudan their numbers are estimated to be in the hundreds of thousands.As a group of evolutionary biologists we conducted a genomic study to understand the complex demographic history and identify signals of adaptive selection among Sudanese people. Our research is the first whole-genome sequencing study carried out in Sudan. This is a method scientists use to read and analyse a person’s complete DNA, the full set of genetic instructions, to understand traits, ancestry and disease risk. Our research covered a total of 125 individuals from five population groups, defined by their language and cultural identity, known as ethnicity. We found that Sudanese Copts showed unusually high resistance to Plasmodium vivax, the most geographically widespread malaria-causing parasite. This protection comes from a genetic variant they acquired after mixing with local Nilo-Saharan people. Similar examples of recent adaptation to malaria after population mixing have previously been reported in Madagascar, Cabo Verde and Pakistan. But this is the first time such a process has been documented within mainland Africa itself. The selection signal observed in Sudanese Copts is among the strongest ever detected in humans. These findings show that strong natural selection can reshape the human genome very rapidly and that recent demographic history is crucial for understanding present-day genetic patterns. These can help explain differences in disease susceptibility across populations, informing medical research and public health strategies.Human migrations in the regionThe expansion of Arabic-speaking people in north Africa started in 639 CE in Egypt and gradually moved southward. It intensified between the 10th and 11th centuries with the migration of Bedouin groups into north Africa and Nubia. By the 16th century, the spread of Arab culture and Islamic faith contributed to the collapse of the last Christian kingdoms in the region.But some populations remained in more isolated areas and preserved their own languages and cultural traditions. These include Nilo-Saharan-speaking groups in Darfur, around the Jebel Marra mountains, and Kordofanian speakers from the Nuba Mountains. These mountainous regions also acted as partial genetic barriers. They limited interactions with surrounding populations. Today these populations show little or no genetic influence from the Arab expansion. Our study confirms this pattern reported in previous studies. With the use of whole-genome sequencing data, our findings further strengthen this insight.Adaptive selection to malaria protectionOur study indicates that around 1,000-1,500 years ago, the ancestors of Sudanese Copts intermarried with local Nilo-Saharan groups. The geographical barrier is not applied for all Nilo-Saharan speaking groups, only for those from Darfur. Copts could have admixed with other groups with a Nilo-Saharan origin but living in a more accessible area. The individuals from Darfur are the group in our dataset that better represent these ancestors, but that does not mean they are their direct ancestors. Through this mixing, they acquired the Duffy-null allele. This is a genetic variant (one of the different versions of a gene) that is widespread in Africa south of the Sahara.This allele is a classic example of natural selection in humans, showing strong geographic differentiation between African populations and the rest of the world. The Duffy-null allele prevents the expression of the ACKR1 receptor, a protein found on red blood cells, used by P. vivax to enter and infect these cells. Individuals who have inherited the allele lack this receptor and are therefore protected against this form of malaria.Because the Duffy-null allele is rare among north African and Middle Eastern groups, it would not be expected to be prevalent in Copts. However, our findings show that about 89% of Sudanese Copts carry it. Our study shows that after admixture with local populations, the variant was introduced into the Coptic population. Natural selection meant it was passed down through generations and became more common. Having the allele gave people a survival advantage in a malaria area. Sudan reported over half million cases of P. vivax malaria in 2017. There is little or no information on regional variation, but the presence of the adaptive variant in Darfur does not necessarily mean adaptation occurred there. This provides a clear example of a genetic population adapting to disease, occurring within the past 1,500 years.Fixing Africa’s under-representationOur study also identified more than one million previously unknown genetic variants, over 1,500 of which may affect genes and their functions. This highlights a major gap in global genomic databases. These are still heavily biased towards people of European ancestry, although Africa harbours the greatest genetic diversity. North Africa, in particular, has often been overlooked.It’s important to know more about the genetic heritage of different populations because, as the Coptic resistance to malaria shows, it can guide medical research and help understand human evolution better.Although whole-genome sequencing has transformed the study of human health and disease, truly global representation remains essential. Africa, as the birthplace of modern humans, harbours the greatest genetic diversity on Earth and should therefore be a top priority for genomic research.This study fills important gaps in our understanding of Sudan’s and Africa’s demographic histories and increases diversity in global genetic datasets. It also shows the importance of including recently mixed populations to obtain a fuller picture of human evolution.Hisham Y. Hassan was a co-author on the article.The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.