Does a population bottleneck increase the mutation rate?

I just read an article by R. Brian Ferguson in [1]. The long paper debunks the claims of Cochran, Henry and Harpending in [2] one by one. Naturally, Ferguson did not manage to get [1] published. I agree with Ferguson’s arguments, may be at some issues I would argue slightly differently, but in general he does a good job in refuting [2] and my own findings confirm what [1] says. But there one observation of [2] that Ferguson does not explain off. It is that Ashkenazi Jews have several genetic diseases, which affect shpinglolipids. Ferguson only notes that some other populations, which have experienced a population bottleneck, also have groups of closely related genetic diseases, but he does not speculate what could be the reason for this odd finding.

So, Ashkenazi Jews have several genetic diseases affecting shpinglolipids! I know, that it does not sound so interesting: nobody cares of shpinglolipids. But it is. Looking up what these shpinglolipids are shows that they are some kind of fats that occur mainly in the cell membranes of the brain and nervous tissue. This must be the main reason why [2] was written. Ashkenazi Jews have a group of diseases affecting brains and a reputation of being more intelligent. It is unlikely that by coincidence the founders of the Ashkenazi community would have had so many diseases affecting brain tissue. Therefore [2] argues that the reason must be natural selection: mutated genes were selected, meaning that they must have given an advantage which is greater than the very real disadvantage of these genetic diseases. Consequently, [2] proposes that these mutated genes are recessive and give an advantage for heterozygotes, while homozygotes suffer from the disease.

This already is a weak point in the theory of [2]. Heterozygote advantage is often proposed but seldom shown to be real. The classical and accepted example of heterozygote advantage is the sickle cell mutation: heterozygotes have partial immunity against malaria, but most other cases of heterozygote advantage are unproven conjectures. There is, for instance, the theory that heterozygotes of cystic fibrosis have partial immunity against cholera, but studies have not confirmed this theory. The authors of [2] propose that there is heterozygote advantage for many Ashkenazi genetic diseases and that the advantage is a higher IQ.

So, this is the theory of [2] and [1] shows that the theory is false: the mutations causing Ashkenazi genetic diseases do not give heterozygote advantage and they do not have a positive association with IQ. This conclusion is true even concerning torsion dystonia, which is often claimed to give a higher IQ based on a study from 1967 and its follow ups by the same researcher group. Later research has not confirmed the higher IQ finding.

Yet there is the group of Ashkenazi diseases affecting shpinglolipids and [1] adds that similar groups of related diseases have been found in other populations, which have experienced a recent bottleneck. The reason may be the genetic bottleneck, but not the way it is usually understood to work.

A genetic bottleneck can enrich a mutation in a population in the natural way that if any of the founders have a rare gene it will be more common in the descendants of this founder than in the original population. We would not expect that the founders by coincidence would happen to have several rare mutations of related diseases. It may happen, of course, but improbable events happen seldom. But I propose another way it can work:

Charles Darwin wrote in the Origins of Species of an interesting phenomenon that he had noticed with plants. When he moved a plant into another environment, it typically suffered but also created new variants. That is, as if the plant generated variants, which could have been better adapted to the new environment. We know that some plant species are very difficult to move from one place to another and usually they die if moved, while some other species can be easily moved. This phenomenon depends on the species. It is also not limited to plants. We know that some animal species just refuse to breed in captivity and therefore cannot be bred in a zoo, while some other species adapt easily. I do not know of any observation mentioning that the animals created new variants after being moved to a new environment, but logically it must be so with animals if it is so with plants.

What are these new variants Darwin noticed? Unfortunately DNA and mutations were not known in his time and Darwin could not differentiate between new mutations of genes and new combinations of existing genes. It is possible, though not likely, that Darwin’s plants would have been pollinated by local variants of the plant and in this way had obtained a new combination of existing genes. I would rather imagine that Darwin ruled this out and the new variants were a result of new mutations. Why there would be new mutations?

There would be much more new mutations if cell’s DNA repair mechanisms would not be so good. Moving a plant to another environment causes a heavy stress on the plant and it does not thrive so well for a long time. What does it mean that a plant does not thrive well? It can only mean that cell level mechanisms do not work as well as before: for instance, cells do not get enough water or minerals or something. As DNA repair is a cell level mechanism, we may assume that after the plant is moved, also this mechanism does not work as well as originally and therefore more mutations get through. Most mutations are harmful, but some are useful. This mechanism increases the mutation rate if the environment changes fast. It may be useful for the species by allowing the species to adapt to the new environment, and for this reason this mechanism has survived in the evolution.

What is true of plants would be true of animals. A human is a species that can adapt to many environments easily and different human populations have different mutations. There is every reason to think that these mutations have something to do with adaptation. Yet, many are not positive adaptations. Ashkenazi Jews, Eastern Finns, Canadian French and European Romani are all populations, which have in their recent history had a stage with a small number of founders and each of these populations have distinct sets of harmful genetic diseases. The harmful genes can often be found in other populations, but with a smaller rate, but some of the genes are unique to the mentioned populations.

Ashkenazi Jews have about 40 typical genetic diseases. Ashkenazi Jews experienced a population bottleneck 25 to 50 generations ago. A male generation is typically 30 years, a female generation about 28 years, so the bottleneck was either the founding of the Ashkenazi population around 800 AD or the founding of the Polish Jewish population around 1300 AD.

Eastern Finns also have about 40 typical genetic diseases. Eastern Finns have a small number of founders. The present Eastern Finnish population grew from a small population starting around 1600 AD but there was also an earlier founding effect: the male founders of the Eastern Finns moved to Finland around 0-400 AD. Additionally, all Finns experienced a population bottleneck much earlier.

These population founder effect time frames are rather similar in Ashkenazi Jews and Eastern Finns and so are the numbers of genetic diseases. Genetic diseases affecting fertility of homozygotes disappear slowly from the population because of natural selection unless there is positive selection. The advantage leading to positive selection does not need to be genetically inheritable, it can be culturally inheritable. For instance, a rich family, which carries a genetic disease, may still produce more children than a poorer family. But finally selection will reduce the rate of the disease, since inside cultural classes there is also selection. Thus, seeing so many genetic diseases in populations which recently experienced a population bottleneck, suggests that many of these diseases were created by the bottleneck and not only enriched.

There is some indication that this may be the case. The Tay-Sachs disease is common in Ashkenazi Jews and in Canadian French. It also appears in the general population but as a rare disease. As the mutation is rare, it is improbable that the founders of both Ashkenazi Jews and Canadian French had the rare mutation. Therefore the mutation happened again in these populations, but as the mutation is rare, it should not happen again so often, unless the mutation rate was higher. As the mutation rate is not higher now, it must have been higher for some time after the bottleneck. That’s what I claimed. Let’s take another example:

One of the Ashkenazi genetic diseases is breast and ovary cancer, which is caused by BRCA1 and BRCA2 genes. These genes are involved in DNA repair. If the repair of DNA is weakened, then there are more mutations not only to these DNA repair genes but to other genes as well. Mutations BRCA1 and BRCA2 and Ashkenazi mutations in shpinglolibids did not turn out to be useful, but some other mutations could have been. The error in [2] may be that they looked for heterozygote advantage from the disease genes, where it is not, and not homozygote or heterozygote advantage from other mutated genes.

Ashkenazi Jews may have genetic adaptations to the environment. Indeed, why would they not have? There is some indication that Ashkenazi Jews may be genetically more resistant to tuberculosis. There are claims for a higher genetic IQ, though I think they may be misinterpreted results showing effects of selection, not mutations. There are national differences in character, as in almost anything.

Not only Ashkenazi experienced a bottleneck: Indo-Europeans invaded Europe some 5000 years ago. Most of the invaders were men. There were only some thousands of men, who replaced most of the male lineages in Europe. As the invaders moved into a new environment, they must have experienced similar effects as the Ashkenazi Jews. What genetic adaptations could this have created? It does not seem that it was the IQ. Europeans without this Indo-European genetic impact have about the same IQ. If there was an effect in mental processes, it could have been in the character. Maybe these people were more social than the two older populations of Europe. One older group was the European Mesolithic hunter-gatherers. They derive from several genetically distinct hunter-gatherer groups, but one may assume that they were not that social. The silent Finns derive from these people. The second group of Europeans was the descendants of Anatolian farmers. The Sardinian people derive from these farmers and Sardinians are stereotyped as reserved and silent. So, where did many Europeans get this easy-going and social character they certainly have?

Actually there were all the time population bottlenecks and small founder populations in the human prehistory. These events could have almost fully determined human evolution: evolution would have happened as punctuated evolution after a change of environment. More of these founder effects would have occurred in the colder climates, where the population would more often almost vanish. This would have boosted the IQ of Europeans and East Asians. It is not impossible to think that a similar effect would have increased the IQ of Ashkenazi Jews, provided that their measured higher IQ is genetic and caused by mutations and not by genetic selection or environmental factors. The case of Ashkenazi IQ is presented in [2] and it is very weak, but the more general possibility that human evolution was punctuated is very possible. Much of human evolution was evolution of IQ, so the main thesis of [2] can be to some extent restored, but I doubt it is so much of IQ, it is of personal character. Let’s dig up all the national stereotypes and pay them a good scientific look as there is a theory to test.

 References:

[1] R. Brian Ferguson, “How Jews Became Smart: Anti-“Natural History of Ashkenazi Intelligence”, https://www.ncas.rutgers.edu/sites/fasn/files/How%20Jews%20Became%20Smart%20%282008%29.pdf

[2] Gregory Cochran, Jason Hardy, and Henry Harpending. 2006. Natural history of Ashkenazi Intelligence. Journal of Biosocial Science 38:659-693:1-35.