Monday, January 28, 2008

Skin pigmentation gene alleles — Part 2

Reviewing H. Norton, R. Kittles et al, 2006 - Part 2:

Link to the part 1: Skin pigmentation gene alleles [clickable]

Additional notes:

For those who are curious, the authors of the aforementioned skin pigmentation study [Kittles et al.] don't specifically point out the TMRCAs for the identified genes in question, but apparently ancestral lineages were delineated from their derived counterparts. From extrapolation though, it makes sense that mutations that occurred after divergence of any given groups, would be relatively rare in the common ancestor of these recently diverged groups. On the other hand, certain mutations that were present within the common ancestor may be expressed more acutely later on in one or the other group that diverged from this ancestral population, while dying out or becoming relatively rare in another progeny group. Still these developments are able to assist one in delineating the frequency and mutational particulars of the genes controlled by natural selection and/or the pressure of genetic drift.

As for "Southwest Asian" populations, they generally fall into ranges contained within the Saharo-tropical Africans, while some northerly groups of this region apparently have relatively paler skin shades as a product of more recent migrations into the region. Kittles et al. at least in part, attribute such developments to gene flow from Northern Eurasia and perhaps, in some areas, East Asia. See again, from my last post:

Concerning the "derived" SLC24 A5 gene...

In contrast, the SLC24 A5 11*A-derived allele is found at low frequencies in several sub-Saharan populations including the West African Mandinka and Yoruba, the Southern African San, and South West Bantu.

The relatively **high frequencies** of the derived allele in **Central Asian, Middle Eastern, and North Africa** seem likely to be **due to recent gene flow** with European populations.

Similarly, the presence of the derived allele (albeit at low frequencies) in some sub-Saharan populations may be due to recent gene flow from European and Central Asian populations. Alternatively, the derived allele may have lost in the ancestors of modern East Asians but retained in the ancestral European populations. The allele then rose to high frequency in Europeans following the divergence of Europeans and East Asian ancestral groups.

Many places outside of Africa, for instance, harbor the 'derivative' counterparts of several "pigmentation" genes [a variety of which have been associated with relatively lighter pigmentation], while ancestral alleles [many of which have generally been associated with relatively darker pigmentation] are commonly found in Africa and amongst direct descendants of earliest out-of-Africa ancestors of modern non-Africans, as is the case with OCA2 gene...

In general, the derived allele (associated with lighter pigmentation) is most common in Europeans and East Asians, and the **ancestral allele** predominates in **sub-Saharan Africa** and **Island Melanesia.**

...and this quite likely applies to "southwest Asians" harboring "derived" OCA2 which has been associated with playing a role in lightening skin phenotype, for example.

Lightening effect was apparently a gradual process, as populations started expanding to low UV radiation latitudes. This is readily seen in the intermediary situations between adaptations on opposite poles of empirical tests; see for example:

High Fst values [concerning the three genes TYR, MATP and SLC24A5] between Europeans and darkly pigmented populations such as West Africans and Island Melanesians are not unexpected if these genes have functional effects. However, the notably elevated pairwise Fst values relative to East Asians (the population in our panel that is the most similar to Europeans in pigmentation phenotype) is striking. Populations intermediate in pigmentation (Native Americans and South Asians) also exhibit Fst values falling in the top 5th percentile of their relevant Fst distributions with Europeans for these three loci. In the case of SLC24A5 A111G, South Asian pairwise Fst values also fall in this top 5th percentile when compared to both Europeans (Fst = .389,  p < .01) and East Asians (Fst= .519, p < .01), but not when compared to any other population. At all three loci Europeans have the highest frequency of the derived alleles relative to the other five populations.

The South Asians being referred to here, comprised of east Indian samples, which are claimed to be 'intermediate' along with the Native American samples. The phenomenon described above, seems to suggest that the alleles at the three said loci in the said 'intermediate' groups predate those attained in both East Asians and Europeans; as noted, their Fst values are not quite as high when compared with any other population [which would essentially be the dark populations]. Apparently, the pigmentation distribution in these 'intermediate' groups reflect demographic events distinct from those that produced the more dramatic pigment-oriented phenotypic manifestations in Europeans and East Asians respectively; being that they possess alleles that post-date OOA migration events, and yet those that predate extreme pigment-related adaptations sported by Europeans and East Asians, they are bound to report intermediary patterns. One might recall that the Native American OCA2-derived allele frequency was said to be comparatively lower than that of East Asians...

Interestingly, derived allele frequencies at this locus are quite different between Native American (15%) and East Asian populations (45%), suggesting that perhaps the derived allele at this locus did not reach very high frequencies in East Asians until after the colonization of the Americas

And might also recall that KhoiSans on the other hand, reported high frequencies of OCA2-derived...

The lightly pigmented hunter-gatherer San populations of Southern Africa is exceptional in having a high frequency of the derived allele relative to geographically proximate and more darkly pigmented African populations (Jablonski and Chaplin 2000), further supporting the importance of OCA2 in regulating normal variation in pigmentation. The widespread distribution of the derived allele in the CEPH-Diversity Panel suggests that it is not necessarily a new mutation, nor has it been restricted to a specific geographic area.

So yes, the derived version of OCA2 likely predates the often-talked about Upper Paleolithic OOA migration in varying frequencies in different populations, but likely did not pick up in distribution dramatically in East Asian and European populations, until after a section of central-East Asian had left for America, in a wave(s) following that of the first Paleo-Americans. This suggests that one drift episode [perhaps amongst the earliest for this type] raised its frequency considerably in at least one African group [the Sans], another drift episode raised its distribution in vicinity of central and/or east Asia to reasonably visible levels, but yet another drift episode raised its distribution even further in east Asia at a later time. All this paints gradual evolution in skin pigmentation relaxation temporally, in tandem with territorial shifts amongst populations.

And recalling...

The discordance between our Fst -based divergence values and allele frequencies in the Melanesian CEPH populations at ASIP largely stem from the relatively low frequency of the ancestral allele in the 2 CEPH Island Melanesian populations relative to our original Island Melanesian sample. These discrepancies make it difficult to determine if ASIP truly underlies broad pigmentation differences between darkly and lightly pigmented populations or instead inter-population variation at this locus can largely be explained by differences between Africans and non-Africans

The answer is rather obvious, no? It reflects the basal phylogenetic position of Melanesians, which is why they'd share ancestral ASIP alleles with continental Africans. The difference then here, would be one of the basal phylogenetic position of Africans vis-a-vis OOA-derived populations, with the deepest-clade bearers of all OOA-derived groups carrying over basal African alleles outside of Africa.

More on the "derived" SLC24 A5 gene...

On the above piece, in one personal encounter, a question had come up along the lines of:

...because one of the authors says not enough time has passed for mutations? And just how is it the author would know this? Since the author, or one of the authors didn't specifically say how much time
has to pass for mutations then I'm asking explain to me what you know they meant by this.

The natural answer to that question, as the present author put forth, was this:

Yes, the authors reckon that "not enough time has passed for mutations" and don't specify "how much time has to pass for [new] mutations" to occur, nor need to, because they determined this from the fact that the DNA flanking the gene in question lacked variation in the samples they studied; the tacit idea here, is that the DNA locus in question not only indicates selective pressure of the gene SLC24A5, where by the flanking DNA in question must have been part of a selective sweep, but its lack of variation suggests that not enough time has accumulated since such a selective sweep would have occurred; otherwise, more variation, however modest, would be expected of a designated DNA locus that has been around for a considerable length of time. And oh, it must be suggestive of some linkage disequilibrium in the inheritance of this assemblage of DNA.

On Jablonski :

The weaker the ultraviolet light, the fairer the skin. Jablonski went on to show that people living above 50 degrees latitude have the highest risk of vitamin D deficiency. "This was one of the last barriers in the history of human settlement," Jablonski says. " Only after humans learned fishing, and therefore had access to food rich in vitamin D, could they settle these regions." — The evolution of race was as simple as the politics of race is complex, By Gina Kirchweger

And to that, the present author says:


Side notes:
The very "relaxed" eumelanin concentration in the skin of 'pale skin' individuals is the expression of their relatively "recessive" alleles, vis-a-vis the more "dominant" counterparts of those that instruct for more production, to produce the considerable skin eumelanin concentration of dark skin individuals. The present author has come across comical claims about the aforementioned "recessive" counterparts "masking" the effects of the more "dominant" skin pigmentation alleles, no doubt from individuals who are in the dark about the basics of genetics. The case in humans, whereby one comes across skin tone gradients, from extreme dark to extreme paleness, can best be described as one of the interplay of "incomplete" dominance of the 'wild types' over their "recessive" counterparts in subjects of "intermediate" skin tones, via polygenic inheritance—wherein the individual effects of "dominant" or "wild" alleles that produce greater eumelanin dosage, will mask those of the relatively "recessive" counterparts in normal "heterozygous" [so to speak, for simplification purposes] subjects, while the "wild" or "dominant" allele types will simply instruct for considerable skin eumelanin in "homozygous" dark skin subjects, and that of the relatively "recessive" allele types instruct for little dosages in "homozygous" pale skin subjects. Now of course, common sense should tell one that these terms "recessive" vs. "dominant" are relative terms, for we know that even in individuals where 'pale skin' is product of natural selection, as opposed to genetic mishap or disorder, the alleles which instruct for only modest eumelanin dosage, if we had two copies of the same alleles from each parent, then neither is dominant or recessive to the other; however, one such allele in the presence of a "wild type" from a darker skin parent, will tend to be "recessive" relative to the said "wild type". All the said alleles in this case, will instruct for eumelanin dosage, but the 'wild type", and hence more "dominant" type, will instruct for bigger dosages than the other allele, the "recessive" counterpart. For those needing basic illustrative demostration, check this site out:

Gist: If one is recessive, it has to be recessive relative to another, and likewise, if one is "dominant", it has to be so over another. It is just common sense.

1 comment:

Brandon Pilcher said...

"The relatively high frequencies of the derived allele [the genetic allele coding for light as opposed to dark skin] in Central Asian, Middle Eastern, and North Africa seem likely to be due to recent gene flow with European populations."

Are there any lineages, either paternal or maternal, widespread in Southwest Asians and North Africans, that can be traced to Europeans?