The spread of the European lactase persistence allele

[pmokeefe]

The spread of the European lactase persistence allele
by Iain Mathieson
12 October 2019
The lactase persistence allele
In European ancestry populations, the LCT/MCM6 locus on chromosome 2 exhibits one of the strongest signals of a hard selective sweep in the entire genome (Grossman et al. 2013, Mathieson et al. 2015). This is assumed to be due to selection on the derived A allele of rs4988235 (i.e. the T allele of -13910 C>T) which is associated with adult lactase persistence (Ennatah et al. 2002), allowing the digestion of lactose—and thus unfermented milk—into adulthood. This is a plausible hypothesis, particularly since different mutations with similar phenotypic effects have arisen independently several times (e.g. Ranciaro et al. 2014). However, the reason for selection remains somewhat unclear and none of the proposed hypotheses (access to energy content, hygiene, vitamin D or calcium, etc… ) seem completely convincing (See Szpak et al. 2019 for example).

Observations from ancient DNA
Ancient DNA has shown that the persistence mutation did not, as one might have assumed, arrive in Europe with the first farmers and actually only became common in the Bronze Age, many millenia after the domestication of cattle and the start of dairying (Burger et al. 2007, Mathieson et al. 2015, Mathieson & Mathieson 2018). With the large aDNA datasets now available, we are able to track the spread of the allele, at least in some parts of Western Eurasia with very high temoral and spatial accuracy. In principle, this allows us to put constraints on the time and place at which selection operated, and perhaps to support or disprove some of the hypothesis about the drivers of selection.

[palamede]

I see they haven't take into account LP results for samples from Spain (Alava or Rioja ) around 3000BC and Scandinavia as stated by Alberto and jeanlohizun in their comments of https://eurogenes.blogspot.com/2015/...cient-dna.html .

[rms2]

I seem to recall there were some real doubts expressed about those Spanish LP results by one of the big name geneticists. I'm sorry I can't recall who it was. It will come to me later, no doubt, or maybe someone else will remember.

[parasar]

I seem to recall there were some real doubts expressed about those Spanish LP results by one of the big name geneticists. I'm sorry I can't recall who it was. It will come to me later, no doubt, or maybe someone else will remember.

Mathieson himself.

"There are earlier reports of the LP allele in the Iberian Neolithic (Plantinga et al., 2012) and even earlier Middle Neolithic Sweden (Malmström et al., 2010). I’m mildly skeptical of these results because 1) They only estimate contamination from mtDNA, rather than the autosomes 2) rs4988235 is a C->T SNP where T is the derived allele, so aDNA damage could be an issue ...
https://mathii.github.io/review/2015...nd-ancient-dna

[rms2]

Mathieson himself.

"There are earlier reports of the LP allele in the Iberian Neolithic (Plantinga et al., 2012) and even earlier Middle Neolithic Sweden (Malmström et al., 2010). I’m mildly skeptical of these results because 1) They only estimate contamination from mtDNA, rather than the autosomes 2) rs4988235 is a C->T SNP where T is the derived allele, so aDNA damage could be an issue ...
https://mathii.github.io/review/2015...nd-ancient-dna

Thanks! That was it. I knew I remembered those remarks, I just could not quite recall the details.

[davit]

The spread of the European lactase persistence allele
by Iain Mathieson
12 October 2019
The lactase persistence allele
In European ancestry populations, the LCT/MCM6 locus on chromosome 2 exhibits one of the strongest signals of a hard selective sweep in the entire genome (Grossman et al. 2013, Mathieson et al. 2015). This is assumed to be due to selection on the derived A allele of rs4988235 (i.e. the T allele of -13910 C>T) which is associated with adult lactase persistence (Ennatah et al. 2002), allowing the digestion of lactose—and thus unfermented milk—into adulthood. This is a plausible hypothesis, particularly since different mutations with similar phenotypic effects have arisen independently several times (e.g. Ranciaro et al. 2014). However, the reason for selection remains somewhat unclear and none of the proposed hypotheses (access to energy content, hygiene, vitamin D or calcium, etc… ) seem completely convincing (See Szpak et al. 2019 for example).

Observations from ancient DNA
Ancient DNA has shown that the persistence mutation did not, as one might have assumed, arrive in Europe with the first farmers and actually only became common in the Bronze Age, many millenia after the domestication of cattle and the start of dairying (Burger et al. 2007, Mathieson et al. 2015, Mathieson & Mathieson 2018). With the large aDNA datasets now available, we are able to track the spread of the allele, at least in some parts of Western Eurasia with very high temoral and spatial accuracy. In principle, this allows us to put constraints on the time and place at which selection operated, and perhaps to support or disprove some of the hypothesis about the drivers of selection.

From those maps seems like an EHG thing and something that has undergone recent selection even in the Indus Valley.

[talljimmy0]

Looks very Bell Beaker-ish

[Granary]

The maps are a bit strange in their time period chosen.