Skin color and Neandertals

Qiliang Ding et al., (2014) published a paper (Neanderthal origin of the haplotypes carrying the functional variant Val92Met in the MC1R in modern humans, Molecular biology, DOI:10.1093/molbev/msu180) which looks into the pale skin of Eurasians in general as due to admixture between Homo sapiens and Neandertals.

The color of our skins is due to the combination of two pigments, one red (phaeomelanin) and one black (eumelanin), and the proportion of this color blend is in part defined by the Melanocyte-stymulating hormone or MSH. MSH is encoded by a gene called MC1R.

If the function of this gene is altered by mutations, it impacts on MSH and therefore on skin color.

Five "loss-of-function" variants of MC1R have been discovered to date, and are linked to fair hair (red or blond) and fair skin:

1. Val60Leu (rs1805005*T)
2. Val92Met (rs2228479*A)
3. Arg151Cys (rs1805007*T)
4. Arg160Trp (rs1805008*T)
5. Asp294His (rs1805009*C)

Neanderthals also carried (but we, modern humans don't), another variant of MC1R (Arg307Gly)

Qiliang's team found that "...almost all of the derived alleles at the Val92Met variant of MC1R (rs2228479*A) in the human gene pool are carried by the putative introgressive haplotypes", by "putative introgressive haplotypes" they mean "haplotypes from Neanderthal introgression in modern Eurasians".

It is found at roughly 5% introgression rates in Europeans (not very high), up to 30% in East Asians (Chinese for instance) and at a surprising high introgression rate of 60 to 70% in the Taiwanese aborigine people (the Atayal and the Ami).

They don't know why this cline exists and conjecture: " Therefore, we cannot rule out demographic effects such as population bottleneck as an explanation for the unusually high frequency of rs2228479*A in Atayal and Ami although positive natural selection is also a possibility"

Its origin is linked to the Altai Neanderthal branch and the time line is the following:

"Based on the values, it could be estimated that the putative introgressive haplotypes diverged with the AMH 552.5 ka, then diverged with the Denisovan 159.0 ka, and then diverged with the Altai Neanderthal 103.3 ka (fig. 2). It could be observed that the divergence time between the putative introgressive haplotypes and the Altai Neanderthal (103.3 ka) postdates the reported Neanderthal–AMH divergence time (>270 ka), which indicates the presence of postdivergence introgression"

Altai, Japanese and Africans

The paper reports that "Remarkably, it was observed that all putative introgressive haplotypes carry the derived allele of the Val92Met variant (rs2228479*A), and almost none [except a Japanese subject NA19084_a]... of the nonintrogressive haplotypes carries the rs2228479*A. This suggests that the rs2228479*A carried by the putative introgressive haplotypes might be from archaic hominin lineage. However, rs2228479*A was not found in the Altai Neanderthal genome."

They explain the lack of rs2228479*A in the Altai Neanderthal as follows: " 1) The rs2228479 is polymorphic in Neanderthal populations, and 2) the mutation creating rs2228479*A occurred on the putative introgressive haplotype shortly after it entered modern human gene pool (...) The rs2228479*A was found in one (out of 41) sequencing read of Altai Neanderthal and one (out of 20) sequencing read of Denisovan. All of the relevant sequencing reads and base calls passed quality control filter. Therefore, it could be possible that the Neanderthal and Denisovan are heterozygous at the rs2228479, and some unknown reason caused the imbalanced observation of ancestral and derived alleles of rs2228479 in sequencing reads."

The Japanese subject NA19084-a is among the non-introgresses subjects, so the derived allele at rs2228479 "might be from recurrent mutation, double recombination, or biased gene conversion".

Interestingly they found this allele at rs2228479 in three African subjects: "...among all HapMap African individuals, it was observed that one YRI (Yoruba in Ibadan, Nigeria; NA18852) and two MKK (Massai in Kinyawa, Kenya; NA21339 and NA21574) carry heterozygous alleles at the rs2228479".

They propose three possible explanations for this odd situation:

"Presence of derived alleles at Val92Met (i.e., rs2228479*A) in Africans could be explained by three models: 1) The rs2228479*A existed in the human gene pool before the Neanderthal–AMH divergence and was drifted to very low frequency in modern Africans whereas preserved in the Neanderthals and modern Eurasians (i.e., the “ancestral polymorphism model”), 2) recent gene flow from modern Eurasians to Africans, or 3) independent origin (such as recurrent mutation)."

They reject (1) but consider (2) and (3) as feasible. That is, it originated independently in Africa or there was a recent flow into Africa carrying Neanderthal genes i.e. contemporary Eurasians, which is quite reasonable, nevertheless, I would add, Neanderthals could have entered Africa and mixed there with Massai in Kenya and Yoruba in Nigeria.

Another surprising find was that it appears ata 50% frequency among the Cheyenne people of America. That is high, and rather unique in the New World, where it is hardly found at all.

Below is a map with its global distribution:

It is important to point out that Norton, Werren, and Friedlaender,(2015) found this Val92Met polymorphism in over 600 Melanesians sampled on different islands, reporting that the frequency of the derived allele ranged from 4 to 33% yet it seemed to have no influence whatsoever on the skin or hair color of the individuals. This suggests that it must interact with other genes to define the tone of hair and skin.

The same thing can be seen in East Asians: they have black hair just like Africans - and unlike brown of fair haired Europeans- despite carrying this derived gene that promotes fair hair.

Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2019 by Austin Whittall © 

Hominins in the Philippines 709,000 years ago: watercraft?

This paper published in Nature a few weeks ago: Earliest known hominin activity in the Philippines by 709 thousand years ago, by T. Ingicco et al. (Nature volume 557, pages 233–237 (2018) doi:10.1038/s41586-018-0072-8) is amazing: the authors find stone tools and the remains of butchered megafauna several hundreds of thousands of years older than expected. These hominins were not Homo sapiens, and the Philippines was separated from the rest of Sundaland by open sea. So how did they get there? Did they use boats?

The paper says the folowing:

• The remains are between 631 and 777 Ky old. So this is +600 ky older than the alleged Out of Africa event of modern humans.
• They found dozens of stone tools, rather primitive, lacking retouching.
• They also found rhinoceros bones with cut marks and percussion marks (to break the bones), a clear indication of hominin activities.

The authors write: "Our excavations at Kalinga and the numeric dating results clearly provide securely dated evidence for human colonization of the Philippines by the early Middle Pleistocene epoch, and long before the appearance of modern humans in both the local context and wider Island South East Asia region. Although the identity of these archaic toolmakers remains unknown, it is likely that they dispersed over at least one sea barrier to reach Luzon Island. The most likely points of origin are Borneo through Palawan to the west, or China through Taiwan to the north, this latter island was connected to mainland Asia during periods with low sea levels..."

Then they wonder if these hominins are related to more recent remains found at Callao Cave, those of a small adult human:

"...a question clearly linked to our discovery is the origin of the Callao Cave hominin that has been dated to 66.7 ± 1 ka. This diminutive Callao hominin may represent a direct descendent from a Pleistocene migration stock related to these early Kalinga toolmakers—similar to what happened on Flores Island—or may be derived from a more recent migration wave of anatomically modern humans..."

The Callao Cave hominin was reported (New evidence for a 67,000-year-old human presence at Callao Cave, Luzon, Philippines,Armand Salvador Mijares et al. Journal of Human Evolution Volume 59, Issue 1, July 2010, Pages 123-132 https://doi.org/10.1016/j.jhevol.2010.04.008) after the discovery of a metatarsal bone (foot bone) of a diminutive hominin, which may have been or not a modern human:

"[The] metatarsal definitely belongs to the genus Homo. Morphometric analysis of the Callao metatarsal indicates that it has a gracile structure, close to that observed in other small-bodied Homo sapiens. Interestingly, the Callao metatarsal also falls within the morphological and size ranges of Homo habilis and H. floresiensis. Identifying whether the metatarsal represents the earliest record of H. sapiens so far recorded anywhere east of Wallace’s Line".

So it may have been a Homo habilis or even a Flores hominin! or, as the authors of the most recent find suggest, a migration of Homo erectus (see below) that became tinier due to insular dwarfism, see what Ingicco et al say about the rhino slayers:

"Despite the current evidence, it still seems too farfetched to suggest that H. erectus, or another unknown Pleistocene ancestral candidate for the Kalinga toolmakers (for example, Denisovans), were able to construct some sort of simple watercraft and deliberately cross sea barriers to reach these islands. However, considering evidence of overseas dispersal during the Middle Pleistocene stage is increasing in number, such a hypothesis cannot currently be rejected."

For me the important thing is precisely that: they crossed open sea to reach the Philippines. This means they dominated the art of building and sailing watercraft long before humans appeared, at the time that Neanderthals were splitting from the ancestors of H. sapiens (if the Out of Africa theory is correct). But do note how hesitant the authors are, to admit this (they write "too farfetched" instead of admitting that they did build a boat...)

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2018 by Austin Whittall © 

Unique Amerindian Genetic Trait

My previous post dealt with the anomalous prevalence of Alzheimer's Disease among American Natives, today's deals with another "unique" Amerindian genetic trait, that extends to what in USA are known as Latinos (people with mixed ancestry that includes Native Americans): one that protects against breast cancer.

Breast Cancer incidence by Race USA. From [1]

The table above clearly shows how American Natives and Latinos have the lowest incidence of Breast Cancer among American women.

The cause according to a paper [2] by Laura Fejerman et al.,(2014) is a mutation in chromosome 6: "Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5′ of the ​Estrogen Receptor 1 gene (​ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53–0.67, P=9 × 10−18), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25."

This mutation is the reason that "Latina women, those with a high proportion of Indigenous American ancestry are at a lower risk of developing breast cancer..." [2].

This mutation must have appeared in America otherwise the purported ancestors of Amerindians (as per the Out of Africa theory) would also carry this variant. By the way, the prevalence of Cancer among Amerindians is almost 1/3 of that found among White American women and half of that found among African American women. The Asian Americans' ratio is also almost twice that of American Natives. (these are supposedly the closest genetic relatives to Amerindians).

Is this also due to a bottleneck? or is did it appear during the "Beringian standstill"?

What does the genome of Neanderthal or Denisova tell us about this mutation? I have tried to find information but have not found anything. It may be a mutation inherited from them. Found only in America.

But what about Papuans, who have a high proportion of Denisovan genes? I found two papers (here) and (here) which inform extremely low levels of cance: roughly 8 to 20 times lower than the ratio among Ameridians"!: from 1958 to 1988, the incidence of breast cancer was betwenn 6.9 and 2.4 per 100,000 women.

Do Papuan women have a genetic mutation that protects them too? or is it just lifestyle? Or are these numbers not adjusted by age?

I found another interesting source (global Cancer atlas) which lists cancer prevalence among all human populations. I selected Breast Cancer Incidence and got this map:

Clearly this differs from the other information: dark blue= EU, Australia, America and NZ, Argentina... countries with a high prevalence of White Europeans that eat beef. And low prevalence in "poor" countries where fatty foods are not so common... Asia, Africa, Bolivia. The quality of the data is also variable, ranging from "A" in the US to "C" in China or "G" in Bolivia (19.2 per 100,000 cases) so it makes me wonder how reliable this information is.

Anway, the intersting point is the mutation in Chromosome 6 found among Native American women.

Sources

[1] Zhang and Olopade in Hereditary Breast Cancer. Edited by Caludine Isaacs, T.Rebbeck. pp.234
[2] Laura Fejerman, et al.,(2014). Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25, Nature Communications 5, Article number: 5260 doi:10.1038/ncomms6260

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2014 by Austin Whittall ©