LACTOSE TOLERANT: A mutation completely independent of one that confers the ability to digest milk in northern Europeans evolved recently and rapidly in East African cattle herding communities Image: ¿ W. PERRY CONWAY/CORBIS
For many adults in the world, the phrase "got milk?" is quickly followed by "got a nearby toilet?" Lactose, the primary sugar in milk, is a universal favorite in infancy but into adulthood the level of lactase-phlorizin hydrolase, the enzyme that metabolizes lactose in the small intestine, decreases and digestion of dairy products becomes difficult. In some populations, however, such as those located in northern Europe, the ability to digest milk remains most likely as a result of lifestyles based around cattle domestication. In 2002 Finnish scientists localized the genetic mutation that conferred this trait in northern Europeans to two regions on chromosome 2.
Now, the results of a four-year, international research project find that communities in East Africa leading traditionally similar pastoral lives evolved their ability to drink milk rapidly and independently of the northern Europeans. According to University of Maryland biologist Sarah Tishkoff, the lead author of a study appearing in today's Nature Genetics, the mutation allowing them to "get milk" arose so quickly and was so advantageous that "it is basically the strongest signal of selection ever observed in any genome, in any study, in any population in the world."
Tishkoff and her students tested 470 people representing over 43 ethnic factions in the Sudan, Kenya and northern Tanzania for lactose intolerance using glucose-monitoring kits, familiar to most diabetics. The team then selected the 40 most lactose intolerant participants and the 69 most tolerant and sequenced parts of their genomes around the two markers identified in the Finnish lactase persistence study. The researchers determined there were 123 single nucleotide polymorphisms--SNPs, or changes to one base in the genetic code--associated with digestibility. Of these, three SNPs were more promising than the others and one of them was very common among Tanzanians and Kenyans, showing up in 40 to 50 percent of the sequences.
Working with this highly correlated locus, Tishkoff's team sequenced a broad region of the chromosome around this nucleotide to determine whether it arose in concert with the European mutation. "It turns out they're on completely different chromosome backgrounds," she explains. "So it had a completely different origin." Next, the team tested to see if the mutation was positively selected, conferring a reproductive advantage and spreading quickly through the population. People who had this particular SNP on both copies of chromosome 2 had identical genetic scripts for the next two million base pairs--a phenomenon that occurs when there is a strong benefit to having a particular trait, known as "hitchhiking" or a "selective sweep." Because this section has been preserved intact without being mutated or broken up by recombination, it indicates that it is very recent and very strong. In addition, Tishkoff's team determined the date range when the mutation likely occurred: 3,000 to 7,000 years ago, which matches up well with the archaeological record that places pastoralization coming to East Africa about 5,000 years ago. The European trait dates back about 9,000 years.
Tishkoff believes that because she found so many markers associated with lactose tolerance in the sequencing of her 109 subjects, evolution clearly develops multiple solutions when there is a strong selective force. "There are some populations that can digest milk, and they don't have any of these mutations," she says. "There are more out there." Dallas Swallow, a human geneticist at University College London, agrees with that assessment. She released a study on a small Sudanese tribe in Human Genetics this past November, finding three markers, two of which Tishkoff had isolated in her study. Oddly enough, Swallow found no data on the Maryland study's primary variant. Tishkoff argues this disparity is due to geographic specificity of these mutations. Swallow, for her part, notes that Tishkoff's dramatic results may be a result of "the relative relatedness" of her sample. "If you have an ethnic group which is rather a small population in size but happens to migrate over geographic distances then they might be more related to each other than the surrounding people," she points out.