Natural selection yes, but for what?

Groups across the political spectrum don’t like the idea that natural selection operates on us. The left because of the monstrosities produced by social Darwinism and eugenics. The devout because we have supposedly been formed by the creator in his image and further perfection is blasphemous.

Like it or not, there is excellent evidence for natural selection occurring in humans. One of the best is natural selection for the lactase gene.

People with lactose intolerance have nothing wrong with the gene for lactase which breaks down the sugar lactose found in milk.  Babies have no problem with breast milk.  The enzyme (lactase)  produced from the gene is quite normal in all of us; no mutations are found in the lactose protein.  However 10,000 years ago and earlier, cattle were not domesticated, so there was no dietary reason for a human weaned from the breast to make the enzyme.  In fact continuing to use energy to make the enzyme something it would never get to act on is wasteful. The genomes of our ancient ancestors had figured this out.   The control region (lactase enhancer) for the lactase gene is 14,000 nucleotides upstream from the gene itself, and back then it shut off after age 8.  After domestication of cattle 10,000 or so years ago, so that people could digest milk their entire lives a mutation arose changing cytosine to thymine in the enhancer. It spread like wildfire because back then our ancestors were in a semi-starved state most of the time, and carriers of the mutation had better nutrition.

Well that was the explanation until a recent paper [ Cell vol. 183 pp. 684 – 701 ’20 ]. It was thought that lacking the mutation you couldn’t use milk past age 8 or so. However sequencing of sites of the herdsmen of the steppes showed that they were using milk a lot (making cheese and yogurt) 8,000 years ago. Our best guess is that the mutation arose 4,000 years ago.

So possibly, the reason it spread wasn’t milk digestion, but something else. Nothing has changed the million nucleotide segment of our genome since the mutation arose — this implies that it was under strong positive natural selection. But for what?

Well, a million nucleotides codes for a lot of stuff, not just the lactase enzyme. Also there is evidence that people with the mutation is linked to metabolic abnormalities and diseases associated with decreased energy expenditure, such as obesity and type II diabetes, as well as abnormal blood metabolites and lipids.

The region codes for a microRNA (miR-128-1). Knocking it out in mice results in increases energy expenditure and improvement in high fat diet obesity. Glucose tolerance is also improved.

So it is quite possible that what was being selected for was the ‘thrifty gene’ miR-128-1 which would our semi-starved ancestors expend less energy and store whatever calories they met as fat.

In cattle a similar (syntenic) genomic region near miR-128-1 has also been under positive selection (by breeders) for feed efficiency and intramuscular fat.

So a mutation producing a selective advantage in one situation is harmful in another.

Another example —

The mutation which allows Tibetans to adapt to high altitude causes a hereditary form of blindness (Leber’s optic atroxpy) in people living at sea level. 25% of Tibetans have the mutation. Another example of natural selection operating on man.

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  • Peter Shenkin  On November 9, 2020 at 12:37 am

    It is pretty common for people who have digested dairy for many years to become lactose intolerant. It happened to me at about age 65. I have read that most people who don’t eat dairy after being weaned become lactose intolerant, and that it is mainly Europeans who can tolerate lactose. The inability to do so used to be called “Jew’s stomach” in Europe. (I’m Jewish, but none of my parents or grandparents had this problem.) So how does the loss of the ability to digest lactose later in life jibe with the evolutionary argument?

  • Anon  On November 9, 2020 at 10:45 am

    My problem with this timeline is that it’s too short (a few thousand years) and there was no mobility back then. How would it spread so quickly? Maybe there’s another underlying reason that we don’t know yet.

  • luysii  On November 9, 2020 at 1:45 pm

    I think there was mobility as farmers from the midEast moved into Europe. Also populations were much smaller then than now, so spread to a high percentage would be faster.

  • Peter Shenkin  On December 30, 2020 at 11:27 am

    I still am skeptical that lactose intolerance is exclusively a genetic phenomenon. I, and others I have known, have become lactose intolerant at an advanced age. How can this be rationalized based on genetics?

    It is also said that, having become lactose intolerance, one can regain lactose tolerance by eating very small amounts of dairy and increasing the dose slowly. I have no experience with this, though, and it’s just something I read, I forget where.

    I suppose that in some unknown way, there could be an epigenetic component.

  • luysii  On December 30, 2020 at 7:33 pm

    My wife developed it a few years ago, and we’ve been married over 50 years. It was very hard when we spent a few weeks in Venice 2 years ago

    • Peter Shenkin  On January 11, 2021 at 2:50 pm

      Some of my friends who are also lactose-intolerant went cold-turkey (or should I say frozen-ice-cream?) on dairy. But I didn’t want to go that far. So I cached in a stock of lactase pills. When I consume dairy, I take one. They really work, so your wife might try them. And if she’s consuming a lot of dairy at once, take two! Note: the generic versions are better than the original Lactaid. They are 3x the strengh per pill, and Lactaid says to take 3 pills, but Lactaid and the generics cost about the same per pill.

      • luysii  On January 11, 2021 at 3:06 pm

        She’s been using Lactaid for years, but some things still remain beyond the pale, including a disastrous event at a wedding.

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