Was red hair selected for fair skin? And how old are MC1R mutations?

In this post we are going to see a couple of points of the study Evidence for Variable Selective Pressures at MC1R, by Rosalind Harding et al., 

This study is from the year 2000, which means it’s now old, but it’s interesting nonetheless, because its conclusions were not entirely wrong.

In 2000, geneticists believed that MC1R mutations gave a major contribution to the evolution of fair skin in Europeans, and for that reason they expected to find a strong selective pressures at this gene. That is, they expected that human evolution selected MC1R because it was useful for people living in areas with low exposure to the sun.

So, they examined several European and non-European individuals. Europeans were from England, Ireland, Sweden, Finland, and Italy. Non-Europeans were from Africa, Japan, Papua New Guinea and southern India.

Here’s what they found out:

Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations under relaxation of strong functional constraint outside Africa.

Their models found no visible selection for MC1R. In particular, before conducting the study, the authors believed that the mutation Arg163Gln had an important role in altering MC1R, but didn’t find any evidence for that.

So, they came to the conclusion that probably MC1R had been the first gene to mutate (as far as human pigmentation is concerned), because there are many mutations that can alter this gene, but, after that, more effective mutations arised in other genes.

As a matter of fact, few years later this idea was confirmed by new discoveries.

Geneticists found out that genes SLC24A5 and SLC45A2 show a far stronger selection than MC1R and they are now considered the main contributors to skin variation in Europeans.

Origins of the SLC24A5 and SLC45A2 based on Archaeogenetics. Derived variants are said to have come from the Caucasus 28,000 years ago

Basically, MC1R underwent what geneticists call soft sweep selection, that is, not one main mutation that replaces all the others, but small mutations that grow all together. Not all of them are effective, though: some may be neutral, or very weak. On the contrary, a gene like SLC24A5 has a main mutation (A111T) showing a hard sweep selection, with a strong signal easy to detect in genomic analyses. The main mutation of SLC45A2 (L374F) behaves similarly.

The 2025 study The Genetics and Evolution of Human Pigmentation (Guermazi and Saliba) is about that too.

The authors write that in Eurasia selective pressure at MC1R had been weak, allowing for a great number of mutations, while in Europe a lighter skin pigmentation is due to genes SLC24A5 and SLC45A2 (in Asia, other genes are involved in skin pigmentation).

So, basically, MC1R is not the main driver for skin variations, but, unlike other genes involved in pigmentation, it shows a great variability.

To put it simple, there must be other reasons why red hair exists.

Let’s now come to the second part of the study,

First of all, the authors argue that both African and non-African data suggest that the time to the most recent common ancestor (TMRCA) of MC1R is ∼1 million years: that is, they are referring to the common ancestor of current MC1R mutations (see also Coalescent theory).

Second, the authors estimate the ages of MC1R alleles.

To estimate the ages of MC1R alleles, we assumed that their observed frequencies simply reflect genetic drift in constant-size, randomly mating populations, after allowing for different patterns of functional constraint.

Basically, researchers assumed that the size of ancient populations remained constant over time, but this may have biased the results given by the mathematical models.

Here are the estimated ages:

variants Val60Leu, Val92Met, and Arg163Gln: 250,000–100,000 years ago;

variants Arg151Cys and Arg160Trp: 80,000 ago;

African silent variants Leu106Leu, Cys273Cys, and Phe300Phe: 110,000–40,000 years ago;

variants Asp294His and Ser316Ser: ⩽30,000 years.

I quote from the study:

However, an incompatibility arises between estimated ages in the range of 250,000–100,000 years, for non-African MC1R allelic variation, and ages, from fossil evidence, of ⩽100,000 years for the dispersal of modern humans outside Africa and the Middle East (Stringer and Andrews 1988). One possible explanation for incompatible ages from genetic data is that they have been overestimated under an assumption of levels of genetic drift that are consistent with constant population size. These age estimates would be younger under an alternative model with a high rate of population expansion out of a Eurasian founding population.

That is, they argue that, since, according to the theory Out of Africa II, the dispersal out of Africa took place around 80/70,000 years ago, these ages are too old, so to speak, and this probably happened because they assumed a constant-size population. 

In subsequent years, other studies have been released that have revised these estimates downwards. This time they used a different demographic model, involving so-called bottlenecks and a rapid growth just after the dispersal out of Africa (although I don’t understand why a population should grow rapidly just after the dispersal out of Africa).

With this new model, the estimates for the first MC1R mutations lowered to 20,000/15,000 years ago.

However, it is important to notice that these new studies are not focused on the MC1R gene and its mutations (like the 2000 study by Harding et al), but rather on multiple genes involved in human pigmentation, and on ancient DNA in general (see, for example, The Timing of Pigmentation Lightening in Europeans, by Beleza et al, 2012).

Besides, since MC1R has got many mutations, dating all of them can be difficult. In any case, since MC1R too is involved in pigmentation, a study like the one by Beleza et al. can be useful to understand MC1R as well.

As for the estimate of 1 million years for the common ancestor of current mutations, modern studies prefer avoiding such a precise date (1 million years), in favour of a more nuanced estimate (500,000/1 million), but they do recognise that MC1R alleles are more ancient than other genes involved in human pigmentation.

Obviously, all the dates we have seen so far shouldn’t be taken as the gospel, and not only because (as we have seen in a previous article) a complete genomic analysis of ancient remains is often impossible.

As far as archaeogenetics and archaeology are concerned, the theory of Out of Africa II has become a sort of dogma. So, should evidence emerge that disproves the OOA (like MC1R mutations dating back to 250,000 years ago), the evidence is considered wrong and the OOA is never questioned.

Below, you’ll find a book and three articles about this dogma.

Not Out Of Africa, by Mary Lefkowitz (free download here)

African Eve: Hoax or Hypothesis? This article is a bit technical in certain points and features a lot of citations, but if you have the patience to read throughit, you’ll see it is very informative.

The two articles below are a bit technical too. 

Re-Examiningthe “Out of Africa” Theory and the Origin of Europeoids(Caucasoids) in Light of DNA Genealogy

Re-Examining the Out-of-Africa Theory and the Origin of Europeoids (Caucasoids). Part 2. SNPs, Haplogroups and Haplotypes in the Y-Chromosome of Chimpanzee and Humans