Thursday, August 09, 2007

Lactase persistence in Eurasia   posted by Razib @ 8/09/2007 11:40:00 AM

At my other blog I have a long post reviewing the new paper on lactase persistence in Eurasia. The authors conclude that the allele which confers most of the latcase persistence in Eurasia arose among "Caucasian" populations. The question is whether the authors meant Caucasian in the 1930s physical anthropological sense (i.e., Caucasoid-Mongoloid-Negroid), or in the more precise sense of peoples from the Caucasus. Here is the portion of the paper which might "clear" this up:
We also monitored the prevalence pattern of the less common LNP [lactase non-persistence -ed.] H87 haplotype that, on the basis of the MJ network, represents the immediate allelic haplotype on which the LP H98 mutation occurred. The highest frequencies of H87 alleles were observed among Daghestan Nogais (8%) and Hazara (7%). This allele was detected in Daghestan Nogais, Hazara, Baluch, Sindi, Brahui, Makrani Baluch, Iranians, Basques, individuals from Utah, and Finns (eastern region). From this distribution of H87, we were able to propose that the ancestral population in which the LP T-13910 H98 mutation occurred is of Caucasian origin.

The Daghestani Nogais are a Turkic group in the Caucasus. None of the rest are technically Caucasian groups. Here are the populations that exhibit H87 with the percentages and N's:

Hazara 7 28
Baluch 5 38
Iran 3 42
Kalash 3 60
Sindhi 2 56
Basque 2 170
Makrani Baluch 2 58
Utah 2 184
Pathan 2 56
Brahui 1 60

The N's aren't as big as you'd like (I know, this is like saying "I'm not as rich as I wish I were!"). H87 is a haplotype one mutational set away from H98, the modal variant associated with lactase persistence throughout Eurasia. The haplotype two mutational steps away from H98 (see the chart on my other blog), H84, has high frequencies throughout Eurasia, but its center of gravity is shifted toward the east (i.e., France has a far lower proportion than China). I think that this implies that H98 and the dominant LP genetic profile arose somewhere in the heart of Eurasia, probably the north-central regions.

Now, one thing that I am curious about are the non-modal alleles, some of which seem to be independent mutational events from a different genetic background than H84/H87. As noted before these variants are:

1) Very new (on the order of 2,000 instead of 8,000 years ago for the most recent common ancestor).

2) Rather rare. Here are the percentages in the populations which exhibit the haplotypes associated with the more recent mutational event. I've also included to the right the percentage in the older cluster, and finally the N's:

Udmarts 15 14 60
Mokshas 11 14 60
Erzas 5 20 60
Iranian 5 2 42
Parsi 4 6 58
Baluch 2 34 38
Somali 2 1 158
Arabs 1 5 102
Southern Italy 1 4 200
Basque 1 58 170
Morocco 1 13 180

What to say here? First, the highest frequencies are found in populations along the Urals. Iranians also seem to have high frequencies of the newer alleles. I am curious about the relative balance between the older and newer alleles in several of the higher frequency populations. If the older variant exists why would the newer one rise in frequency over the past few thousand years? If the older variant exists why did it not sweep to fixation? If the selection pressure was too weak (or various balancing forces maintained polymorphism) to fix the older variant why did the newer mutational event begin to rise in frequency in the first place? Here are some thoughts:

1) LP is weird. It has to come with some cost, probably metabolic. With the domestication of cattle any costs were overridden by the benefits of adult milk consumption. Perhaps the new mutational event has associated functional elements around T-13910 which make them a better solution? Perhaps there are regulatory elements which mask some of the negative correlated responses due to this mutation?

2) The populations which have the highest proportion of LP (northwest Europe) don't seem to exhibit the new variants. What gives? The selection pressure is obviously strong for anything that confers LP. We know that some African and Middle Eastern populations have other LP conferring SNPs besides T-13910, but the major groups above already had that, and, they were likely to be near the source of the rise of frequency of the mutant in the first place (judging by the distribution of H84/H87). Perhaps there is selection pressure for LP around the Urals (extant diary culture), but there are other forces which prevent its increase (maintain polymorphism). So the new mutant and associated haplotype might be a response to (counter) pressure #2. Pressure #2 might not be operative in western Eurasia so it is just another neutral allele because it doesn't have any fitness boost.

3) It seems suspicious to me that it seems likely that both clusters arose in central Eurasia. It isn't like there are more cosmic rays or enormous populations churning out mutations here. My own suspicion would have been that central Eurasia would just have a diversity of descendants from the original mutant from H87, but that doesn't seem like what's going on. A de novo mutational event occurred. Don't know what to make of that. There's other things lurking the background.