Is Lactose Tolerance Just a Broken Gene?

[swamidass (S. Joshua Swamidass)]

Continuing the discussion from Should I Debate Kevin Anderson on Common Ancestry?:

Can someone give me the papers behind this question?

@dsterncardinale

For example, he claims that the most common mutation that confers lactase persistence does so because it break a repressor gene. That’s absolutely false; the gene in which the mutation occurs codes for a helicase subunit, and the lactase persistence mutation is in an enhancer within an intron of that gene. So he’s wrong on two fronts: The mutation doesn’t inactivate the gene in which it occurs, and that gene is not for a lactase repressor.

[davecarlson]

See for example:

In recent years, a number of single nucleotide polymorphisms (SNPs) have been found in association with the LP [Lactase Persistance] trait in different populations. The first to be identified, −13910 * T , is found not in the LCT gene (the lactase gene) but within an intron of a neighbouring gene, MCM6 [23]. In vitro studies indicate that this nucleotide change affects lactase promoter activity [24,25] and thus is highly likely to cause LP, although it is currently not possible to exclude tight linkage disequilibrium with another, as yet unobserved, functional variant. An interpolated map showing the global distribution of −13910 * T can be seen in figure 1 b , using published data [14,15,26–30] supplemented with recently collected data. A cursory comparison of figure 1 a , b shows that while the −13910 * T allele may explain the distribution of LP in Europe, it cannot explain the distribution of LP in Africa or the Middle East. Indeed, Mulcare et al . [31] showed this formally using a robust statistical framework, and other studies have identified additional LP-associated alleles that explain much of the distribution of LP in Africa [16,20,32]. Interestingly, all these variants are located within 100 nucleotides of −13910 * T in the same intron of the MCM6 gene, a region that is functionally important for the expression of lactase in vitro [24,33]. Because these various LP-associated alleles are found on several different haplotypic backgrounds [14,20,34], it is now clear that LP has evolved multiple times and is thus an example of convergent evolution [35].

From 10.1098/rstb.2010.0268

Note that the MCM6 gene referenced above is part of the helicase MCM complex.

edit: fixed link

[dsterncardinale]

OH and I got the goods on Anderson on this one. My apologies for linking one of my own videos, but it’ll start at the right time for this topic:

https://youtu.be/_zfrpsQoJ80?t=435

I especially like how he appears to start saying “repressor” but catches himself.

[T_aquaticus]

For those like me who need the crutch of multi-colored figures:

10.4: Lactase Persistence Colwin Yee

[CrisprCAS9]

It is important to note that each of the variants is individually sufficient, and it is likely the case that many others with the same effect are possible.

[T_aquaticus]

@CrisprCAS9

It is important to note that each of the variants is individually sufficient, and it is likely the case that many others with the same effect are possible.

Very good point. It is a good example of how we can detect convergent evolution, and also an example of the plasticity of function. From the article @davecarlson cited:

Interestingly, all these variants are located within 100 nucleotides of −13910 * T in the same intron of the MCM6 gene, a region that is functionally important for the expression of lactase in vitro [24,33]. Because these various LP-associated alleles are found on several different haplotypic backgrounds [14,20,34], it is now clear that LP has evolved multiple times and is thus an example of convergent evolution [35].