The Evolution Of Lactase Persistence

UPDATE: The Bell Beaker Behemoth paper data casts grave doubt on the conjectures made in this paper about the LP gene's source, means of expansion, and fitness effects.

Lactase persistence-the ability of adults to digest the lactose in milk-varies widely in frequency across human populations. This trait represents an adaptation to the domestication of dairying animals and the subsequent consumption of their milk. Five variants are currently known to underlie this phenotype, which is monogenic in Eurasia but mostly polygenic in Africa. 

Despite being a textbook example of regulatory convergent evolution and gene-culture coevolution, the story of lactase persistence is far from clear: Why are lactase persistence frequencies low in Central Asian herders but high in some African hunter-gatherers? Why was lactase persistence strongly selected for even though milk processing can reduce the amount of lactose? Are there other factors, outside of an advantage of caloric intake, that contributed to the selective pressure for lactase persistence? It is time to revisit what we know and still do not know about lactase persistence in humans.

Segurel and Bon, "On the Evolution of Lactase Persistence in Humans." 18 Annual Rev Genomics Hum Genet. (April 19, 2017 [Epub ahead of print which is anticipated on August 31, 2017]).

Hat tip to Bell Beaker blogger.

The Conventional Wisdom

LP genes are rare in the first farmers of Europe, but become present at a very high frequency in Western Europe around the time of the Bell Beaker expansion. Conventionally, it has been assumed that the European LP variant evolved in situs in Northwest Europe in the Late Neolithic/Early Bronze Age and increased rapidly in frequency because it conferred greater selective fitness. 

Two Reasons To Doubt The Conventional Wisdom

But, two things have cast doubt on the conventional wisdom. 

First, it has become clear that the Bell Beaker expansion and Corded Ware Expansion both involved, at about the same time, massive migration and at least significant partial replacement of existing populations with people who have significant ultimate European steppe pastoralist ancestry. 

This migrationist reinterpretation of the Bell Beaker phenomena implies that it is possible that an LP gene already present at reasonably high frequencies in the steppe ancestors of these people may have ridden piggy back on the selective fitness advantages associated with being part of a Bronze Age technology, dairying civilization. These people had huge cultural advantages that conferred selective fitness among people who use stone tools, who were ancestrally farmers whose food production methods have experienced a collapse, who used cattle primarily as a labor source and source of meat. These cultural advantages may not have been instrumentally related to their LP phenotype. A small part of the rise in LP frequency may have involved instrumental benefits associated with this gene, but mostly it is a marker for being in a more technologically advanced culture that is growing in market share and absolute numbers in Western Europe.

The extreme growth in LP frequencies in this time period in Europe, in other words, looks a lot like it was driven to a significant extent by a founder effect that takes hold right at the bottom of one of the most severe bottlenecks in European population history. Note also that if the subset of the population driving the expansion of the Bell Beaker culture across Western Europe had significantly higher than average levels of the LP gene due to random chance, relative even to the population in which Bell Beaker ethnogenesis occurred, this founder effect could be particularly strong.

For example, suppose that Bell Beaker ethnogensis occurred in Iberia ca. 2800 BCE when three hundred pre-Bell Beaker men and thirty pre-Bell Beaker women migrate there with most of the pre-Bell Beaker men marrying local women, and that 30% of the resulting Proto-Bell Beaker people in Iberia have the LP gene. But, suppose that 80% of the expansion of the Proto-Bell Beaker culture into Western Europe arises from 20% of the Proto-Bell Beaker population and that 70% of the people in this rapidly expanding subset of Proto-Bell Beakers have the LP gene. In a scenario where there is near total replacement of the prior first wave Neolithic population with expanding Bell Beaker people as there was in England, the frequency of the LP gene could go from nearly zero, to more than 60%, extremely rapidly, even in the LP gene, instrumentally had no selective fitness benefits. 

If the LP gene had at least some modest instrumental selective fitness benefits (which seems much more plausible than the conventional wisdom in which it is a decisive factor in likelihood of survival all by itself), it might easily rise in frequency in Eastern Europe to 65% to 70% over the 40 to 60 generations during which the Bell Beaker culture endured relative to the baseline 60% frequency it would have had if it was ancestrally informative but selectively neutral. A shift from 60% to 67.5% over 50 generations (i.e. about 0.15 percentage points per generation on average) looks a lot less impressive than a shift from less than 1% to 60% to 70% over 65 or so generations (i.e. 1 percentage point per generation on average).

Of course, this only works if the steppe population ancestral to the pre-Bell Beaker migrants had some appreciable level of the LP gene developed over many generations in a resource poor steppe pastoralist context where the adult LP phenotype might have had greater selective fitness benefits than it did in Bronze Age Western Europe by about 3000 BCE. So far as I know, there is not much ancient DNA evidence to support this hypothesis, yet, but not enough data to rule out this very plausible hypothesis either. 

If this is how the LP gene came to be so common in Western Europe, it also provides another line of evidence strongly disfavoring an ancestral origin of the pre-Bell Beaker people linked to pastoralists in North Africa (such as Nilo-Saharan peoples) where different LP genes arose than the one that is the predominant source of the LP phenotype in Europe.

N.B. These percentages are merely gross estimate place fillers used to illustrate the concept and not actually documented historical percentages (apart from the less than 1% frequency of the LP gene pre-Bell Beaker).

Second, the increase in the frequency of the LP gene is so great, over so short a time period in the ancient DNA record that it is hard to imagine any realistic scenario that would give it such an intense selective fitness enhancing effect - pretty much unrivaled in the history of human evolution.

Death from insufficient caloric intake is primarily a scourge of young children who can drink cow's milk whether or not they have the LP gene which only impacts ability to drink milk without incident as an adult. Immune benefits associated with vitamin D may be real but vitamin D deficiencies (which are a particularly issue in higher latitudes) aren't that huge of a mortality risk inducing factor these days in adults, although infectious diseases were definitely a much bigger mortality risk from the Neolithic era right into the early 19th century, than they are today, even among adults, although most infectious disease deaths historically also involved children for whom the European LP gene should be irrelevant.

Also, as the article notes, since foods like cheese and yogurt that make dairy products usable for adults who lack the LP phenotype were made as far back as the early Neolithic, it is hard to see why avoiding this modest food processing burden would have such a huge effect on the mortality rates of adults in the Bronze Age.

Nobody doubts that the LP phenotype enhances selective fitness at the margin, but it just doesn't make sense that it should be the most fitness enhancing trait there ever was unless it repelled some virulent pathogen that was as deadly to adults as it was to children which evolved in parallel to become far less deadly to adults even in the absence of LP over the next 1,500 to 1,000 years.

In contrast, it is easy to see how the membership in a culture whose package of comparatively advanced technologies and perhaps also forms of social organization brought by the Bell Beaker people to Western Europe in  this time period could confer extremely enhanced selective fitness.

Historical Narratives That Explain The Seeming Paradoxes

This isn't necessarily inconsistent with the low levels of LP gene frequency in Central Asian populations today. The LP phenotype is rare in Eastern Asia and Central Asia's demographics have been heavily influenced by multiple waves of Altaic migration from the East in the last couple of thousand plus years - first by linguistically Turkic populations and then by the Mongolia Empire. And, in these East Asian pastoralist cultures, the horse was more central than the cow, for example, with fermented horse milk as a culturally important drink. So, even if Central Asia had high levels of the LP gene when it was filled with people who were mostly ancestrally West Eurasian, those levels may be low now due to a population turnover in favor of ancestrally East Eurasian people. Empirically, there is a pretty gradual cline in relative shares of East Eurasian and West Eurasian ancestry along the historic Silk Road today.

In Africa, different LP genes evolved more or less independently of those in Europe, especially in pastoralist Nilotic populations, and there has been more introgression of genes from pastoralist Nilotic populations into hunter-gatherer populations than the other way around, and has been more of an exchange of genes between Nilotic pastoralists and hunter-gather populations whose ways of life and world views are more similar to each other, than there has been between sedentary farmers and hunter-gatherers whose lifestyles and world views are more disparate. So, it makes sense that African hunter-gatherers currently have significant frequencies of LP genes even though this adds little selective fitness in a culture that does not keep dairy cows and does not buy cow's milk for adults in large quantities from cultures that do.