Monday, January 01, 2007

Got milk?

I hope you readers have a good 2007.

While at dinner with family over the holidays, I observed a little something. Now, if you take a pack of wild wolves (or gorillas or something else), if they obtain a meal, there is a fight for the tastiest/best morsels of food, and the least desirable food is left for last. If a solitary animal finds food, it too gobbles up the best part of the meal, saving or leaving the less desirable rest.

It probably was the same for the hunter-gatherer humans of old. Find food, eat the best, and leave the rest for later. Probably, as food security increased, humans became less worried about not getting the tastiest morsels, and so were less worried about gobbling food up. Well, I’ve been domesticated to such an extent that I usually save the tastiest portions of the meal for last, so that I can relish it at leisure, savoring the smell and taste, taking in small bites, and allowing it to linger.

I wouldn’t last a day in the wild.

Anyway, coming to probably a more interesting result of natural selection; agriculture and domestication of animals dramatically changed human life, and certain traits have rapidly evolved in humans due to this. One of them is a tolerance for lactose, and the ability to drink milk as an adult. Most mammals drink milk as infants, but are then weaned away from milk. However, many of us drink milk with out any problems as an adult. The reason for this is that lactase phlorizin hydrolase (LPH), the enzyme that breaks down lactose (the major sugar in milk) in to glucose and galactose, is expressed in us as adults. In most mammals, the expression of this enzyme is shut-down or repressed as adults.

But many, many people in the world are lactose intolerant, and cannot handle milk. Lactose intolerance is high among Africans, Native Americans and East Asians. Lots of researchers have tried to find out the genetic reasons for lactose intolerance, and varying degrees of lactose intolerance in populations. The gene that codes for LPH is long known, and researchers surprisingly did not find too many differences or mutations in the coding region of the gene (the part that actually becomes a functional protein) across populations. About four years ago, a group found a single specific mutation (a single nucleotide polymorphism, where a cytosine in the DNA was mutated to a thymine) in a completely different gene, MCM6, in Finnish populations that surprisingly had an effect on the expression of LPH, and therefore lactose tolerance. Since then, it is widely believed that this mutation is what gives Europeans lactose tolerance.

However, this mutation was not as prevalent in southern European or Middle Eastern populations, and very rare in African populations, which were also lactose tolerant. So, could there be other mutations that also cause tolerance to lactose? A group of researchers examined over forty African ethnic groups, and for starters searched in the same general region as the earlier mutation, and found three new variants all of which were associated with lactose tolerance. Additionally, their study also showed different mutations spread across different populations, with more pastoral populations having much stronger lactose tolerance, and a clear positive selection for one of the mutations (that provided lactose tolerance).

This study is a really nice example of convergent evolution . One can imagine a tremendous benefit to humans who acquired lactose tolerance. Once animals were domesticated, the meat was an obvious source of food, but the milk was a ready and highly nutritious (and sustainable) source of food as well. So, it clearly benefits pastoral societies to develop tolerance for milk at adulthood. In order to obtain the same outcome (lactose tolerance) nature came up with different was to achieve it. Different mutations all lead to lactose tolerance.

(This reminds me of my school days, where we had to prove theorems in class, in physics or mathematics. We knew the answer (g=9.8 m/s2), but some of us came up with extremely innovative methods to obtain that solution. Beautiful convergent evolution).

This study is really quite nicely done, and suggests how much variation is likely for what were likely “important” needs under strong natural selection. There’s one large population of people closer to home that I’m betting is going to have a lot of variation for SNPs determining lactose tolerance. South Asians. Dairy products are an essential part of every meal (as ghee, yogurt, milk, and every dessert), and India has more cows and produces more milk than any other country. Given the sheer diversity of populations in India, with differences in dietary habits, I’m very curious to know if a majority of the population carries a single mutation conferring lactose tolerance, or if (just like the country itself) there is tremendous diversity in mutations that provide tolerance.

(Read the original research paper here (Nature Genetics - 39, 31 - 40 (2006) )

11 comments:

apu said...

Interesting. Would it also mean that for such varying means to achieve the same end, the groups needed to be not in contact with each other/spread across geographies? How would this play out in the subcontinent which was a more closed land, where I am assuming there were would have been some amount of mingling between various groups?

Sunil said...

apu....good but complex question. For convergent evolution, it is entirely possible for it to happen without the groups being in contact with each other. But, genetically, in order to achieve the same final result (or phenotype), often more than one possible mutation is possible. So, different mutations can give the same final outcome. This is driven by the selective pressure that demands that outcome.

In the subcontinent, most peoples were in close contact with each other. So, it is much easier for a group to develop a phenotype, and this spread through marriage etc.

SDRocks said...

Sunil, I have read that ~75% of North Indians are lactose tolerant, while only around 25% of South Indians are. Now here's a charged question for you - is there a racial origin for this (Aryan vs Dravidian!)? Also, most South Indians who are lactose intolerant don't know they are, because they consume copious quantities of curd and buttermilk which contain lactobacilli that help to digest lactose.

Sunil said...

sdrocks.....I cannot comment on that because I don't know enough about it. But those numbers sound made up, and if you can point me towards a reference, I might be able to put more together. I would doubt that there is a racial origin to it. Way too many modern molecular studies have shown that most Indian populations are extremely racially diverse, and the studies coulnd't find enough significant differences between north or south indians. The trends are worthless. The Aryan vs Dravidian population estimates you might read on a site aren't based on too many scientific details. Historic details perhaps. I'm still waiting for a study that shows clear "Aryan" markers in broad north Indian populations, that don't show up in south Indian "dravidian" populations.

But anyway in any typical population, over 50% of the population will have varying levels of lactose intolerance. Usually, milder forms of intolerance aren't taken too seriously (say milk causes a small excess of gas...it isn't serious enough to make you worry)....so getting good numbers on this is just about impossible.

Anonymous said...

In discussions of the genetics of lactose intolerance (which I follow with interest, as I am one of the unfortunate intolerant), there is a key point which is uniformly overlooked: milk naturally contains lactase enzyme, which is activated by the acidic environment of the gut. It is only since pasteurization, which destroys enzyme activity, has become widespread (and in many places mandatory) that people who don't produce endogenous lactase have trouble digesting milk. I can drink planty of raw (unpasteurized) milk with no difficulty, as can other lactose intolerant peeople.

So what was the real extent of evolutionary selection for maintaining lactase activity into adulthood?

Anonymous said...

What options do we have on lactose intolerance:
http://simplewebsurf.com/lactose-intolerance-symptoms/

Katie said...

I am lactose intolerant. There are a ton of milk subsitutes. I use Rice and Easy. It's a milk made out of whole grain rice and with added calcium and Vitamin D. It tastes good and it's healthy, I am pretty happy with it.

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