Three causal variants of lactose tolerance in Sudanese populations

Lactase persistence has long been of interest to the scientific community. Humans are the only species known where some individuals are able to digest milk throughout their life.

“What is really interesting here is that, compared to other populations with a high proportion of milk-digesters such as northern Europeans or the Maasai of Kenya, where lactase persistence is caused by a single genetic variant, the Beja people carry three different alleles,” says Nina Hollfelder, lead author of the study and a postdoc at Uppsala University.

In the new study, published open access in Genome Biology and Evolution, researchers sequence genetic variants associated with lactase persistence (i.e. lactose tolerance) and discuss their patterns in populations from Sudan and South Sudan.

Lactase persistence among humans

Lactase persistence, the ability to digest milk as an adult, has long been of interest to the scientific community. Humans are the only species known where some individuals are able to digest milk throughout their life. Approximately 20 years ago, researchers identified a single mutation in Europeans to be responsible for this trait. In the following years, additional variants have been identified in milk-drinking Arabic and African populations.

In this study, the researchers investigated all currently known polymorphisms associated with lactase persistence in 18 Sudanese and South Sudanese populations. Populations inhabiting this diverse area practice a variety of different subsistence patterns, with varying dependency on the consumption of milk and milk products, not only from cows but also from camels and goats. 

The landscape of lactase persistence in Sudan

The scientists found that populations that practice agriculture have higher frequencies of lactase persistence-associated alleles. Especially the Beja people inhabiting the Sudanese coastal regions show one of the highest proportions of milk-digesters globally. The uncovered diversity of lactase persistence-associated alleles shows that gene-flow has been one of the drivers that shaped the landscape of lactase persistence in Sudan and South Sudan.

“Our study highlights the importance of northeast Africa to the understanding of gene-culture coevolution. Aiming at higher sample coverage of the region will help us disentangle undiscovered variants that might have been selected for, through the evolution of the lactase gene,” says Hiba Babiker, co-author of the study and a visiting researcher at the MPI-SHH. 

“What is also interesting is that some of the lactase persistence-associated alleles have not been observed in such high frequencies previously,” adds Carina Schlebusch, senior author of the study, an assistant professor at Uppsala University.

Strong positive selection in Europeans and East Africans

Lactase persistence has been shown to be under strong positive selection in Europeans and East Africans, indicating that historically people who were able to digest milk had a higher fitness. In this study, the researchers were able to show that the signals observed in the Sudanese populations are consistent with positive selection.

This is the first time all five lactase persistence-associated alleles have been investigated in Sudan and South Sudan. However, the researchers could not find any evidence for a genetic cause of lactase persistence in the Nilotic people of South Sudan. These populations have repeatedly been shown to be well adapted to milk-digestion.

“This really shows us that lactase persistence in Africa is much more complex than our current understanding. It also demonstrates that more efforts are needed to understand the drivers of lactase persistence in Africa,” says Mattias Jakobsson, senior author of the study and professor at Uppsala University.