the genetics of lactase persistence

Some time ago now I wrote about lactose intolerance in humans & the domestication of cattle. Last year the Schol Bio exam included a question that looked more deeply into lactase non-persistence (which is the normal genetic condition: around 70% of all adults can’t digest the milk sugar lactose because the gene coding for the necessary enzyme is ‘switched off’ in early childhood). The examiner asked students to 

[D]iscuss the presence & occurrence of lactase persistence in different regions of the world. In your discussion consider: the genetics & inheritance of the lactase persistence allele in humans; the role of cultural evolution in the selection of lactase persistence in only certain regions of the world; & the reasons for the current frequency distribution of lactase persistence.

It’s an interesting question & so I thought I’d talk more about the whole lactase thing here.

As I said in my previous post, people first domesticated cattle around 8000 years ago; probably the animals were first kept for meat but at some point farmers thought of using the milk as well. Now, in terms of the human population as a whole, most adults can’t digest the lactose that milk contains, & can be described as lactose-intolerant.. Rather than being broken down into the monosaccharide sugars glucose & galactose (which are small enough to be absorbed across the wall of the small intestine), the lactose passes on to the large intestine where bacteria use it as an energy source. Unfortunately this bacterial fermentation also produces a lot of gas (which can be a bit anti-social & more than a little uncomfortable) & a range of other by-products that can cause considerable discomfort to those concerned. (This includes diarrhoea: the sugars that remain in the gut raise its osmotic potential & this means that a lot of water’s retained in the faeces,with unpleasantly sloppy results.)

It turns out that human lactase production is under the control of a gene on chromosome 2 (which means that it’s not sex-linked). The gene’s switched on in babies – as for all young mammals – & as a result the lactase enzyme is produced in the infant’s small intestine, allowing them to completely digest their milky diet. And, as in all young mammals, there’s a developmental pattern of gene expression in the small intestine: the gene is turned ‘off’ (ie the DNA is altered in a way that means that the gene cannot be expressed) when the infant is weaned. In other words, this change in gene expression is induced by an environmental change – an example of epigenetics. The result is ‘lactase non-persistence’ in the majority of human adults. However, this non-persistence is neither universal nor distributed evenly in human populations. Instead, lactase persistence is the norm in some parts of the world, and for most people in these populatins the lactase gene remains active, continuing to express lactase in the small intestine.

It seems that the gene remains active in these individuals because they all carry a dominant mutation that prevents the permanent inactivation of the lactase gene. (‘Dominant’ means that the mutation is expressed in everyone who carries at least a single copy of that allele. For a ‘recessive’ allele to be expressed you need to have 2 copies of it – unless it’s sex-linked, that is.) What’s really interesting, in terms of the early history of agriculture, is that this mutation has become fixed in more than one regional population. It appears to have occurred – quite independently – in populations in northern Europe & also in parts of Africa, around the same time that milk cattle were domesticated in these areas. Now, realistically this mutation could have occurred many times over. But it wouldn’t have become fixed in a population until environmental conditions meant that it conveyed a selective advantage – in this case, the ability to digest milk & milk products, & thus take advantage of a novel source of protein, vitamins, & calories not available to the rest of the population. Bear that in mind when you look at the following map.

The distribution of lactose-intolerance is shown on the image below (if you click on it you’ll get to a higher-res form), where bright red represents the highest frequency of lactase-intolerant individuals (91-100%) & hence the highest frequency of lactase non-persistence. Bright green shows the lowest frequency (0%) [& apologies to those of my readers who are colour-blind! Blame wikipedia…].


So, let’s look in a bit more detail at the distribution of lactase non-persistence (shades of red) & persistence (shades of green). The high frequency of lactase persistence in parts of Europe & North Africa is related to the fact that these are areas where dairy farming was independently ‘invented’. Once people thought of drinking milk, those with the mutant allele that allows lactase persistence would be at an advantage because of their ability to access a good-quality source of nutrients & calories. If they produced more children, on average, than non-milk-drinkers, & some of those children carried the mutant allele, then it would spread through the population & milk drinking would become more common.The similarly high frequency of the allele in North American and Australasian populations can be put down to high migration rates from Europe.

There are of course exceptions to that last statement. Indigenous populations in both North America & Australia have a high frequency of lactase non-persistence, as do African Americans. Not to mention Asia & southern Africa: for an excellent Schol answer you’d need to suggest a reason for all this.

For the indigenous populations of Australia & North America, lactase non-persistence (& thus lactose intolerance) would be expected to be at high frequency in the populations because these are areas where early human populations did not develop dairying. Thus there’d have been no selection pressure & no ‘fixing’ of any ‘persistence’ mutations that occurred. You could also suggest that until recently there’s been little gene flow into these countries from the areas where dairying developed (with the resultant high frequency of the lactase persistence allele). It’s also likely that until recently high gene flow didn’t equate to high levels of interbreeding (necessary to introduce the persistence allele into indigenous populations). And you could also suggest that, for African Americans, the source of Africans taken to the US by the slave trade would have something to do with it.

See? I said it was an interesting question 🙂

3 thoughts on “the genetics of lactase persistence”

  • It is an interesting question, one with a lot of history and interesting little corners.
    I read somewhere that the difference between European and North-African lactose-tolerance may possibly relate to use of camel’s milk rather than from cattle, as well as the different populations. A bigger picture I placed this in (see URL on my name) is that looking at these genetic variants (and that of disease organisms), a picture of human migration and relationships merges. If you like, the gene flow can tell you something about population movements and mixing too. (Or, alternatively populations that did not move or mix.)
    I’d need to check, but I believe you can add Pacific Islanders to populations that have relatively low levels of lactose tolerance.

  • So, forgive my possible complete misinterpretation (Theatre/English major!), but would it be fair to say that since many of the groups with lactase non-persistence would now be regular consumers of dairy products (for example, as Grant mentions, Pacific Islanders), and the instance of lactase persistance has not risen in these groups, that consumption of dairy products no longer gives one an evolutionary advantage?
    Or is it too recent to say?
    (as a mostly-vegan I have a personal interest in the topic!)

  • Alison Campbell says:

    Could be – a modern healthy diet might provide sufficient nutrients that you can get away without dairy. Or it could be that these groups haven’t been consuming milk for long enough – a few hundred years max – for natural selection to have had any effect on de novo mutations in the cohort in question…

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