The Cheddar man is a 9,150 year old fossil from the Cheddar Gorge in England. In 1996 Bryan Sykes found out that it had mtDNA U5. The whole genome of this early hunter gatherer was decoded in 2018 and now we know that this Mesolithic man had Y-DNA C1a1, that he was lactose intolerant, had dark and curly hair and blue eyes. He did not have the alleles which give modern Europeans their light skin. Originally it was concluded that the Cheddar man was dark skinned, but later evaluations have taken this statement back. Probably he had olive skin.
What I found interesting when looking at this issue was that inheritance of eye color is not so simple as they told in the school and studying it leads to potentially important insight to what makes an allele recessive or dominant. A better idea of that mechanism leads to further insights. In the school I was told that the eye color is inherited in the Mendelian manner. The blue color is recessive and the brown color is dominant. That is how it appears to work, but only appears. It is actually much more complicated, and there are special genes for other eye colors, like green, hazel and so on. There is a general rule that if something is simple and understandable it must be a simplification: nothing is simple in the reality. So it is here.
A gene has a protein coding part and a control part. The control part tells when to code proteins and how much. This control part can be controlled yet by another gene’s control part. In the case of blue eyes what happens is more or less the following. There is the OCA2 gene, which causes oculocutaneous albinism that turns the skin lighter and eyes blue. The expression of this gene in the eye is controlled in modern Europeans by the HERC2 gene. This control gene controls the control part of OCA2 and works only with eyes.
Of course, going to greater detail everything gets very complicated. ( See e.g.: “Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression”
https://link.springer.com/article/10.1007%2Fs00439-007-0460-x )
A gene is turned on or of by proteins called transcription factors. Researchers suggest that a mutated HERC2 gene causes a transcription factor to bind into a new place and this shuts the nearby OCA2 gene from working in eyes. This is just a current theory, but something like this happens. We do not need to go to this detail.
Modern Europeans are not albinos and do not get light skin from ORC2. They have the special light skin alleles SLC24A5 rs1426654 and SLC45A2 rs16891982 and the Cheddar man did not have these alleles. I could not find information is he had alleles, which give East Asian light skin: OCA2 His615Arg, TYRP2 rs2031526, MC1R rs885479, and ATRN (according to Wikipedia only OCA2 is clearly shown to be the reason of lighter skin in East Asians), but as the Cheddar man was clearly Western European, he probably did not have them. There are still alleles of two genes (ASIP and KITLG) which are higher in both European and East Asian populations. These mutations were created before the populations split. They have some effect on skin color, but only small.
The Cheddar man had an ORC2 allele causing blue eyes and very possibly olive color skin. I think the blue eyes become common because they were connected with a lighter skin that was selected as it helps in getting vitamin D. The other alternatives are a bottleneck effect and genetic drift or sexual selection for blue eyes, but the first two depend on luck and if sexual selection was the reason then it is difficult to explain why in other places blue eyes were not strongly selected. Blue eyes in Caucasus appear as a minority color. I think the best explanation that lighter skin color gave more the D vitamin, but this means that originally these hunter gatherers were some kind of albinos. The albino mutation of OCA2 is the most common albino mutation and especially common in Sub Saharan Africans. They have it in 1/5000. Most forms of albinism result to impaired eyesight, but OCA2 albinism not so much. Later mutations removed albinism and now blue eyes and light skin are not so closely connected in Europe.
So far so good, but what does this example tell about when an allele is recessive? The allele of the HERC2/ORC2 gene (we treat them as one gene for simplicity) causing blue eye color is recessive because the recessive variant does not produce protein P for making melanin in eyes. If you have one original allele making this melanin, then you have brown eyes. If you have two alleles which do not work, then you have blue eyes. A recessive gene is one which does not work: it does not do everything that the original gene did. The problem can be in the control part as in eye color, or in the protein coding part which means that the gene makes incorrect proteins because of a mutation. Again, it does not work.
We conclude, an allele is recessive if it does not do everything the original allele did.
Inversely, a dominant allele either turns on protein coding more often that in the original (you can get e.g. larger ears and longer face as in X associated dominant disease Fragile X, I made a mistake in the previous comment, I meant Fragile X, not Down Syndrome), or turns on some atavistic features that should be off. Good, this just modifies what there was and turns on what was not supposed to be on. We conclude, an allele is dominant if it does more that the original allele did.
So how do you get a completely new property what is needed for evolution? Like how do you create an eye when there was no eye in the beginning? It is very difficult with random mutations. Recessive mutations turn off something what there was, that does not help. Dominant mutations turn on what there was but was turned off, that also does not help. I can see only that some piece of DNA gets multiplied and then a mutation makes it nonfunctional, which does not harm as there is the original piece still working. The nonfunctional piece accumulates in a long time new mutations and miraculously it will one day produce something totally new, like an eye. As can be seen, this is nearly impossible. It is indeed a monkey hitting keys and producing a new working gene.
I think it is important to think how these mutations actually could work, as it reveals that evolution of new species and new properties is not explained. Mutations only explain turning on and off existing functionalities. Natural selection is a fact, but it also does not explain evolution of species to the extent that is believed. Creating a theory out of almost nothing probably will not lead to the correct theory, but the insight that it gives may lead to a correct insight of larger things. Like, you cannot in an armchair guess how eye color genes work, but you may become convinced that evolution in large cannot produce life out of non-life, even with mutations.
One insight is that there is a problem with evolution.
Another insight is that many genes have several alleles. That means that these alleles are not fully recessive or fully dominant. Consider two recessive mutations to the original allele and assume that we are correct saying that recessive alleles do not do everything that the original allele does. Then we have two alleles which lack different functionality. If a person has these two alleles, neither one of them can be dominant, nor recessive. They are partially co-dominant. In fact, this is what we should expect from IQ genes, whether in the X chromosome or in autosomal chromosomes.
How then does a person express autosomal IQ genes? As they are neither fully recessive, not fully dominant, a heterozygote expresses both alleles partially.
What about X associated genes? A male has only one allele of X associated genes and expresses the allele fully. In a female most X associated genes are X inactivated. That means that each cell in a female body randomly selects one allele which it expresses. In that case the female expresses both alleles, but those functionalities which are missing from each allele are expressed in only half of the cells. The result is that the female expresses these functionalities weaker than a male, probably about half as strongly. However, if one allele is lacking essential functionalities but the other allele has them, we see only minor or no effect on a female, while in a male we see the full effect. Thus, a recessive X associated gene in a male can cause mental retardation and appear as fully recessive in a female.
There are some X associated genes, which are not X inactivated. In that case a female expresses them as she would express autosomal genes. If the alleles are both recessive, neither of them is completely recessive, nor completely dominant. They appear as partially co-dominant, each with a weaker effect than in a male.
Finally, there are some parentally imprinted genes, which mean that a female expresses an allele it got from a specific parent. In this case a female expresses the allele fully.
As a conclusion, Mendelian inheritance (dominant, recessive) is strictly speaking correct only in the case of autosomal genes with two alleles: the original and a simple mutation. Recessive X associated genes may appear to follow Mendelian inheritance if the recessive allele causes a serious degradation. This is the case with recessive X associated alleles for mental retardation. As females show X inactivation, this is not true Mendelian inheritance, but looks like it. A recessive (or dominant) X associated allele, which causes only minor effects, will be partially expressed in female heterozygotes.
Because of this, X chromosome associated IQ influencing alleles will cause a stronger effect in males, who have only one allele, than in females, but the frequency of phenotype effect in men and women is not related in the Mendelian way. It is not so that if men express the allele with frequency p then women express it with frequency (1/4)p2+(1/4)p3 as would follow from the Hardy-Weinberg equilibrium as a difference of the carrier frequency and the homozygote frequency. Women probably express it roughly with the frequency p/2.
This leads to the insight that the higher IQ variation in men than in women can be explained by X chromosome associated IQ related genes. I have in another post suggested a simple explanation by for the fact that the average IQ of both sexes is about the same with a small male advantage. This explanation is that men have a bigger brain and thus initially higher IQ, but X associated deleterious alleles lower male IQ all the way to the point when sexual selection stops it: male IQ stays very slightly above female IQ because of assortative sexual selection practiced by women.
Yeah, well, I hope that was all clear and simple. Anyway, they were some highly interesting insights, right? Why do I write these posts? Do I not remember my students saying vähemmän matikkaa, fysiikkaa ja Jormakkaa.