A new study led by University of Pennsylvania researchers — constituting the largest investigation ever of lactase persistence in geographically diverse populations of Africans — investigated the genetic origins of this trait and offers support to the idea that the ability to digest milk was a powerful selective force in a variety of African populations which raised cattle and consumed the animals' fresh milk

Previous research has shown that northern Europeans and people with northern European ancestry, as well as populations from Africa, the Arabian Peninsula and Central Asia with a tradition of fresh milk production and consumption, continue to express the lactase enzyme into adulthood. Some of these earlier studies had traced the genetic origin of this trait in Europeans to a particular mutation that regulates the expression of the gene that codes for lactase. And in 2007 a study examined African populations and found three additional genetic variants associated with lactase persistence that had not been previously identified. But these variants didn't completely account for the reason why some Africans were able to digest milk. To try to reconcile these apparent discrepancies between genotype, the genetic basis of a characteristic, and phenotype, the characteristic itself, researchers led field studies to often-remote areas of Kenya, Tanzania and Sudan to collect blood samples and perform a lactose tolerance test on people from diverse ethnic backgrounds. The idea was that the researchers wanted to sample as many populations, and as diverse a set of populations, as possible. They included pastoralists, agro-pastoralists, agriculturalists and hunter-gatherers, so the four major subsistence patterns were all covered. To look for genetic variations among the populations' abilities to digest milk, the team sequenced three genomic regions thought to influence the activity of the lactase-encoding LCT gene in 819 Africans from 63 different populations and 154 non-Africans from nine different populations in Europe, the Middle East and Central and East Asia. They also examined the results of the lactose tolerance test in 513 people from 50 populations in East Africa. Their sequencing and phenotyping efforts confirmed the association between lactase persistence and three known single–nucleotide polymorphisms, or SNPs, places where the DNA sequence varies in just one "letter." But they also identified two new SNPs associated with the trait located in regions that are thought to regulate lactase gene expression. Their analysis revealed strong evidence of recent positive selection affecting several variants associated with lactase persistence in African populations, likely in response to the cultural development of pastoralism. The distinct geographic patterns in which these variants were present correlate in many cases with historic human migrations, mixing between populations as well as the spread of cattle, camels or sheep. For example, they found the variant associated with lactase persistence in Europeans, T-13910, in central and northern African pastoralist groups, suggesting that these groups may have mixed historically with a non-African population. The age of this genetic mutation is estimated to be 5,000-12,300 years old, coinciding with the origins of cattle domestication in North Africa and the Middle East. And a variant, G-13915, found at high frequencies in the Arabian Peninsula, and also present in northern Kenya and northern Sudan, dates to roughly 5,000 years ago, around the time that archaeological evidence suggests that camels were domesticated in the region. Another variant, G-13907, was identified in the northern reaches of Sudan and Kenya as well as in Ethiopia. The researchers speculate that the mutation may have arisen in Cushitic populations in Ethiopia, who later migrated into Kenya and Sudan in the last 5,000 years. They observed still another variant, C-14010, in Tanzania and Kenya as well as in southern Africa. This variant is believed to have arisen 3,000 to 7,000 years ago, a timing in line with the migration of pastoralists from North Africa into East Africa. The researchers' analysis suggests that this variant spread more recently into southern Africa, perhaps only in the last 1,000 years. Even with the new variants that the team identified, there were still patterns that the genetic data couldn't explain. Some groups that appeared to be able to digest milk lacked any genetic sign of this ability. The Hadza, nearly half of whom had the lactase persistence trait, are one example. This raises the strong possibility that there are other variants out there, perhaps in regions of the genome that haven't yet been examined. Another possibility is that commensal bacteria in the gut could offer humans a helping hand in digesting milk. The team is now assaying Africans' gut bacteria to see if that might be the case.