Female mammals produce milk to nourish their young. Much of the nourishment comes from lactose, the major sugar in milk. The lactose is broken down in the infant’s small intestine into the more simpler sugars, glucose, and galactose, which are readily absorbed by the small intestine. The break-down, or digestion, of lactose is mediated by an enzyme called lactase.
After weaning, a baby rapidly loses the ability to produce lactase. When adults consume milk, cheese, ice cream or other dairy products, many of them experience unpleasant effects like bloating, flatulence, and diarrhoea. This is because the undigested lactose passes into the large intestine, where it is utilised by the bacteria residing there. This produces hydrogen, carbon dioxide, and methane, and the unabsorbed sugars increase water flow into the bowels to produce diarrhoea. These are the hallmarks of lactose intolerance.
Yet millions of people around the world regularly indulge in milkshakes, cheese pizzas, and ice cream sundaes even as adults. This is because they carry genetic mutations that allow them to continue producing lactase even as adults. This trait is called lactase persistence.
A textbook example
The mutations that confer lactase persistence emerged independently in different populations. Their emergence in North European and African populations in particular appears to have coincided with the domestication of cattle, buffaloes, goats, sheep, and other livestock, which began about 11,000 years ago. The cultural shift from hunting/gathering to pastoralism gave continued access to meat, milk, and hides from herds of domesticated animals.
The coincidental emergence of lactase persistence mutations with livestock domestication was taken by many scientists at the time to be a ‘textbook example’ of convergent evolution. That is, the independent evolution of similar traits in distantly related populations. Experts believed it was driven, in the words of a 2007 paper in Nature Genetics, by the “strong selective pressure resulting from shared cultural traits — animal domestication and adult milk consumption”.
A wrinkle in the textbook
Scientists may need to reevaluate this neat summation in the light of new findings reported by a team of researchers from Fudan University in Shanghai, China; the Max Planck Institute for Evolutionary Anthropology, in Leipzig, Germany; and the Université de Lyon in France. Their findings were published in the Proceedings of the National Academy of Sciences.
The researchers found a distinct evolutionary pathway for lactase persistence in East Asian populations, which includes the Chinese, the Japanese, and the Vietnamese. Unlike the gene-and-culture coevolution well-documented in African and European groups, the East Asian lactase persistence gene had come from the Neanderthals, an archaic group of humans that went extinct about 30,000 years ago.
When the researchers conducted population genetic analyses of the part of the genome containing the lactase gene, they found evidence of pre-agricultural selection pressures beginning more than 30,000 years ago. That is, the East Asian genomes began evolving towards lactase persistence several millennia before these populations began to domesticate livestock.
This early evolution likely targeted advantages related to the immune system rather than lactose digestion directly. The researchers found the East Asian (Neanderthal-derived) lactase gene showed the same expression pattern as the mutant responsible for lactase persistence in Europeans. This suggested it also conferred lactate persistence.
Neanderthals in our genome
About 7 million years ago, the evolutionary line leading to the contemporary Homo sapiens diverged from the one leading to our closest living cousins, the chimpanzees and bonobos. About 800,000 years ago, our line split once more: one population broke away and migrated to Eurasia, adapting to cold climes and eventually becoming the Neanderthals. The other stayed put in Africa and, by about 200,000 years ago, evolved into modern humans.
Modern humans migrated out of Africa into Eurasia 120,000 to 80,000 years ago, and came into contact with their Neanderthal cousins there. DNA evidence from skeletal remains dating to after the contact showed the two occasionally interbred as well. As a result, today, about 1-4% of the genome of individuals with Eurasian ancestry — i.e. Europeans, East Asians, Indians, Native Americans, and Oceanians — represents Neanderthal-derived DNA sequences. The lactase gene of East Asians was one such segment. On the other hand, those of African descent have close to 0% Neanderthal-derived sequences.
About 30,000 years ago the Neanderthals went extinct for reasons that are still not clear.
Bones to pick
Experts can distinguish Neanderthal skeletal remains from those of modern humans by the shape of the skull, inner ear bones, and pelvis width. Neanderthal bones have yielded DNA, which scientists have sequenced and compared with that of H. sapiens.
Two random humans share about 99.9% of their DNA sequence whereas humans and Neanderthals shared only about 99.7%. Thus, there are about 9.6 million points of difference between Neanderthal and human DNA sequences, in terms of the bases the DNA is made of. Based on these differences, if a DNA sequence is sufficiently long, one can tell whether it is from humans or Neanderthals.
The Allen Ancient DNA Resource (AADR) is a curated database of more than 10,000 genome sequences from the skeletal remains of ancient individuals who lived up to 20,000 years ago. The researchers who put this resource together have also identified, on every genome, more than a million sites where the DNA has been known to exhibit a different ordering of bases than ‘normal’.
About 67% of the ancient DNA sequences in AADR are from remains recovered in Europe and Russia, some 8% each are from East Asia and the Near East, about 7% are from the Americas, about 5% are from South and Central Asia, about 3% from Africa, and about 2% from Oceania.
A story upended
The researchers behind the new study searched AADR and found one modern human who lived around 14,000 years ago in the Amur area of China. This individual carried the Neanderthal-derived lactase gene. The gene occurred in roughly 10% of those humans who lived 8,000 to 3,000 years ago, and in about 20% of those who lived about 3,000 to 1,000 years ago. Its current frequency among East Asians is 28.9%.
Thus, the AADR data also supported the inference made from the population genetic analyses: that the lactase gene had already experienced selection and had reached a (relatively) high frequency among East Asians long before they began to domesticate animals.
Thus either the selection in East Asians, unlike that in Africans and North Europeans, was for reasons other than lactase persistence, or in all three geographies the selection was similarly not for lactase persistence.
Either way in the light of these findings the classic story of gene–culture coevolution has become more complicated and hence, as the researchers note, more interesting.
D.P. Kasbekar is a retired scientist.
Published - May 13, 2025 05:30 am IST
