Convergent evolution of lactase persistence - part n

Note: I got this article via AJHG's RSS. It doesn't seem to have gone live on the site so there might be temporary problems accessing the link.

Evidence of Still-Ongoing Convergence Evolution of the Lactase Persistence T_-13910 Alleles in Humans:

A single-nucleotide variant, C/T_-13910, located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T_-13910 variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T_-13910 H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T_-13910 H98 allele (~5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (~1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T_-13910 allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

Two things to note

1) A recent common origin for much of the Eurasian lactase persistence phenotype is interesting. The period between 5 and 12 thousand years ago was obviously very significant and an inflection point in many ways in terms of the history of our species. Surveys of neutral markers which are supposedly reasonable proxies for ancestry imply that we should be cautious about mass population replacements across Eurasia. For example, it seems likely that the majority of Europeans and South Asians are descended from lineages already extant within their current geographic bounds at the end of the last Ice Age (though more or less significant impacted by population waves of advance triggered by the Neolithic revolution in the Middle East). Nevertheless, some biologists have argued that the sweeping action across demes of mutations of large effect are powerful enough to maintain species continuity and drive broad phenotypic convergences. One can conceptualize the genetic dynamics at work as a broad substrate of ancestrally informative alleles clustered across Eurasia, but tightly laced together by synchronous sweeps and pulses of functionally salient genes.

2) The newer, localized, LP variants are intriguing. The time window is very narrow here. Evolutionary theory tells us that in reaction to a strong selective force phenotypic change may immediately be affected by mutations of large effect. These mutants may be good at what they are meant to do, but also have negative side effects. Over time various selection pressures will reshape the genetic architecture with a host of modifiers and smaller effect mutants which result in a population subject to less stress via correlated responses due to the initial mutant of large effect. I wonder if the newer variants are signals that the genetic background is still working to optimize adaptation to a high lactose diet.

Related: See here and here.