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Thread: The evolution of skin pigmentation associated variation in West Eurasia

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    The evolution of skin pigmentation associated variation in West Eurasia

    Abstract

    Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans. It is unclear whether selection has operated on all the genetic variation associated with skin pigmentation as opposed to just a small number of large-effect variants. Here, we address this question using ancient DNA from 1158 individuals from West Eurasia covering a period of 40,000 years combined with genome-wide association summary statistics from the UK Biobank. We find a robust signal of directional selection in ancient West Eurasians on skin pigmentation variants ascertained in the UK Biobank, but find this signal is driven mostly by a limited number of large-effect variants. Consistent with this observation, we find that a polygenic selection test in present-day populations fails to detect selection with the full set of variants; rather, only the top five show strong evidence of selection. Our data allow us to disentangle the effects of admixture and selection. Most notably, a large-effect variant at SLC24A5 was introduced to Europe by migrations of Neolithic farming populations but continued to be under selection post-admixture. This study shows that the response to selection for light skin pigmentation in West Eurasia was driven by a relatively small proportion of the variants that are associated with present-day phenotypic variation.

    https://www.biorxiv.org/content/10.1...05.08.085274v1


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    3 members found this post helpful.
    Quote Originally Posted by kingjohn View Post
    Abstract

    Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans. It is unclear whether selection has operated on all the genetic variation associated with skin pigmentation as opposed to just a small number of large-effect variants. Here, we address this question using ancient DNA from 1158 individuals from West Eurasia covering a period of 40,000 years combined with genome-wide association summary statistics from the UK Biobank. We find a robust signal of directional selection in ancient West Eurasians on skin pigmentation variants ascertained in the UK Biobank, but find this signal is driven mostly by a limited number of large-effect variants. Consistent with this observation, we find that a polygenic selection test in present-day populations fails to detect selection with the full set of variants; rather, only the top five show strong evidence of selection. Our data allow us to disentangle the effects of admixture and selection. Most notably, a large-effect variant at SLC24A5 was introduced to Europe by migrations of Neolithic farming populations but continued to be under selection post-admixture. This study shows that the response to selection for light skin pigmentation in West Eurasia was driven by a relatively small proportion of the variants that are associated with present-day phenotypic variation.

    https://www.biorxiv.org/content/10.1...05.08.085274v1

    I just skimmed it, but it's clear he does the same confusing thing he did in his first paper on pigmentation: he doesn't distinguish between WHG and EHG.

    If the EHG had OCA2, for example, but WHG did not, it makes a difference. Same goes for TYRP1. Furthermore, for steppe anybody with 30% steppe ancestry is steppe. Excuse me? The only "steppe" people we should be interested in for pigmentation are the "original" steppe people on the Pontic steppe.

    I'm personally not taking any of that seriously other than to agree that from all other analyses, 24A5 came to Europe with Neolithic farmers.

    What is different is that contrary to other studies he says 42A5 is relatively unimportant. That's the one which was high in EHG, yes? Interesting the importance of BNC2 and CTSC, and the relative unimportance of IRF4.

    I also don't know why he didn't show the data for the 1000 genomes project or the standard component of modern European populations.

    I guess forensic scientists should refigure their algorthms.

    The Heather Norton 2007 paper shows the frequency for three important snps according to him and 42A5.

    file:///C:/Users/Owner/AppData/Local...010_msl203.pdf






    The following is 42A5, which everyone has considered important until now.





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    Quote Originally Posted by Angela View Post
    I just skimmed it, but it's clear he does the same confusing thing he did in his first paper on pigmentation: he doesn't distinguish between WHG and EHG.

    If the EHG had OCA2, for example, but WHG did not, it makes a difference. Same goes for TYRP1. Furthermore, for steppe anybody with 30% steppe ancestry is steppe. Excuse me? The only "steppe" people we should be interested in for pigmentation are the "original" steppe people on the Pontic steppe.

    I'm personally not taking any of that seriously other than to agree that from all other analyses, 24A5 came to Europe with Neolithic farmers.

    What is different is that contrary to other studies he says 42A5 is relatively unimportant. That's the one which was high in EHG, yes? Interesting the importance of BNC2 and CTSC, and the relative unimportance of IRF4.

    I also don't know why he didn't show the data for the 1000 genomes project or the standard component of modern European populations.

    I guess forensic scientists should refigure their algorthms.

    The Heather Norton 2007 paper shows the frequency for three important snps according to him and 42A5.

    file:///C:/Users/Owner/AppData/Local...010_msl203.pdf






    The following is 42A5, which everyone has considered important until now.



    thanks for the table of slc45a2 nice
    very logic to me :)
    if people in england who are 95% derived for it
    make sense
    i visited london when i was younger
    and tell you the truth i felt swarthy there ....
    now i know i am derived for SLC24a5 because i saw in ftdna raw data that i am A/A
    but ftdna don't test for SLC45a2 so i assume i might be hetrozogite for it
    since i am swarthy

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    ^^Well, he thinks it isn't very important. He's the first one not to think it important, however.

    Satsurbia had 24A5, as well as the Anatolian farmers. It then shows up near Karelia, right, among the EHG, where we find the yDna J?

    As far as I'm concerned I think the light skin snps went into Europe in a sort of pincer movement, and then selection acted on them more or less depending on the environment. Drift in certain populations did the rest, as he pointed out.

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    Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation.

    Scandinavia was one of the last geographic areas in Europe to become habitable for
    humans after the Last Glacial Maximum (LGM). However, the routes and genetic composition
    of these postglacial migrants remain unclear. We sequenced the genomes, up to 57×
    coverage, of seven hunter-gatherers excavated across Scandinavia and dated from 9,500±
    6,000 years before present (BP). Surprisingly, among the Scandinavian Mesolithic individuals,
    the genetic data display an east±west genetic gradient that opposes the pattern seen in
    other parts of Mesolithic Europe. Our results suggest two different early postglacial migrations
    into Scandinavia: initially from the south, and later, from the northeast. The latter followed
    the ice-free Norwegian north Atlantic coast, along which novel and advanced
    pressure-blade stone-tool techniques may have spread. These two groups met and mixed
    in Scandinavia, creating a genetically diverse population, which shows patterns of genetic
    adaptation to high latitude environments. These potential adaptations include high frequencies
    of low pigmentation variants and a gene region associated with physical performance,
    which shows strong continuity into modern-day northern Europeans.

    this paper is about the formation of SHG
    they got light eyes from WHG and light skin from Karelian EHG
    but frequencies of both increased through adaptation on high latitudes

    their Y-DNA : I2a1b* and I2a1a2-Y4213
    they survived in Pitted Ware and in Narva cultures
    I2a1a2 didn't go extinct

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    Razib Khan's take on it:
    https://www.gnxp.com/WordPress/2020/...t-pigmentation

    Not particularly insightful in my opinion.

    He's rather late to the party in one thing: we speculated here years ago that we might not know the primary advantage of these snps, and that a lighter skin color was only the byproduct.

    Regardless, it has to be tied to the amount of solar radiation in some way, that, and/or as I have speculated before, the consumption of dairy products.

    There's a reason the people of the Celtic fringe, especially Ireland, are almost translucent. High altitude mountain living also must affect it. Besides admixture and the pronounced drift of isolated places, that might explain the skin pigmentation in my father's mountain areas.

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    Quote Originally Posted by Angela View Post
    I just skimmed it, but it's clear he does the same confusing thing he did in his first paper on pigmentation: he doesn't distinguish between WHG and EHG.

    If the EHG had OCA2, for example, but WHG did not, it makes a difference. Same goes for TYRP1. Furthermore, for steppe anybody with 30% steppe ancestry is steppe. Excuse me? The only "steppe" people we should be interested in for pigmentation are the "original" steppe people on the Pontic steppe.

    I'm personally not taking any of that seriously other than to agree that from all other analyses, 24A5 came to Europe with Neolithic farmers.

    What is different is that contrary to other studies he says 42A5 is relatively unimportant. That's the one which was high in EHG, yes? Interesting the importance of BNC2 and CTSC, and the relative unimportance of IRF4.

    I also don't know why he didn't show the data for the 1000 genomes project or the standard component of modern European populations.

    I guess forensic scientists should refigure their algorthms.

    The Heather Norton 2007 paper shows the frequency for three important snps according to him and 42A5.

    file:///C:/Users/Owner/AppData/Local...010_msl203.pdf






    The following is 42A5, which everyone has considered important until now.



    Here're my results related to these traits.

    My actual phenotype: white skin, green eyes (very little yellow around pupils) and brown hair in adulthood. GedMatch eye color prediction: brown (wrong).
    Father's actual phenotype: white skin, brown eyes, black hair and freckles (more till full age; had carcinoma few years ago).
    Mother's actual phenotype: white skin, green eyes, I guess blond till full age and dark blond in adulthood, or something like that, je je.

    Have 2 siblings with lighter and 2 siblings with darker hair/eyes than myself.

    From the table
    ASIP 8818 rs6058017 -
    Mine and Mother's: AA -> magnitude 0; common in clinvar
    Father's: AG
    OCA2 355 rs1800404 -
    Mine: CT
    Father's: CC
    Mother's: TT
    TYR 192 rs1042602 - CC (all)
    MATP 374/SLC45A2 rs16891982 - GG (all) -> mag 1.1; Generally European; Light skin; Possibly an increased risk of melanoma
    SLC24A5 111 rs1426654 - AA (all) -> mag 2.7; probably light-skinned, European ancestry

    * ASIP
    Near ASIP rs1015362 - CC minus, so equals GG (all) -> mag 2; 2-4x higher risk of sun sensitivity if part of risk haplotype.
    Near ASIP rs4911414
    Mine and Mother's: GG -> mag 0; normal.
    Father's: AG -> mag 2; 2-4x higher risk of sun sensitivity if part of risk haplotype

    * Listed OCA2 and/or mag > 0
    OCA2 rs7495174 -
    Mine and Mother's: AG -> blue/gray eyes less likely
    Father's: AA -> blue/gray eyes more likely
    OCA2 merged rs4778241/rs6497268 - AC (all)
    OCA2 merged rs4778138/rs11855019 -
    Mine and Mother's: AG
    Father's: AA -> mag 1; freckles more likely
    OCA2 rs1800401 -
    Mine and Mother's: GG minus, so equals CC -> mag 1; blue/gray eyes possible
    Father's: AG minus, so equals TC -> mag 1; brown/black eyes more likely
    OCA2 rs1800407 - CC minus, so equals GG (all) -> mag 1; blue/gray eyes more possible
    HERC2 (near OCA2) rs12913832 - AG (all) -> brown eye color
    HERC2 rs1129038 - CT minus, so equals GA (all)

    * Other TYR
    TYR rs1393350 -
    Mine and Father's: GG -> common on affy axiom data
    Mother's: AG -> mag 2;

    * Other SLC45A2
    SLC45A2 rs26722 - CC (all) -> normal

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    ... some SNPs are not the Gospel, ... my eyes are brown, ...

    rs7495174 AA blue/gray eyes more likely




    rs1800407 CC blue/gray eyes more possible



    SNPs from 23andme or AncestryDNA raw-data

    (I checked both files and they match)

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    Quote Originally Posted by Salento View Post
    ... some SNPs are not the Gospel, ... my eyes are brown, ...

    rs7495174 AA blue/gray eyes more likely




    rs1800407 CC blue/gray eyes more possible



    SNPs from 23andme or AncestryDNA raw-data

    (I checked both files and they match)
    Yes. Here, the combination matters the most, rather than a result in isolation. Notice that my father has the same results as yourself for rs7495174 and rs1800407, and he also has brown eyes.

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    Quote Originally Posted by Regio X View Post
    Yes. Here, the combination matters the most, rather than a result in isolation. Notice that my father has the same results as yourself for rs7495174 and rs1800407, and he also has brown eyes.
    One more reference: my wife. She has pure green eyes (without that little yellow).

    OCA2 355 rs1800404 - CT

    OCA2 rs7495174 - AG -> blue/gray eyes less likely
    OCA2 merged rs4778241/rs6497268 - AC
    OCA2 merged rs4778138/rs11855019 - AG
    OCA2 rs1800401 - AG minus, so equals TC -> mag 1; brown/black eyes more likely
    OCA2 rs1800407 - CC minus, so equals GG -> mag 1; blue/gray eyes more possible
    HERC2 (near OCA2) rs12913832 - GG -> mag 2.5; blue eye color, 99% of the time
    HERC2 rs1129038 - TT minus, so equals AA <associated to blue>

    Our kid ended up with something like grey or green. We don't know exactly. lol

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    Quote Originally Posted by Regio X View Post
    One more reference: my wife. She has pure green eyes (without that little yellow).

    OCA2 355 rs1800404 - CT

    OCA2 rs7495174 - AG -> blue/gray eyes less likely
    OCA2 merged rs4778241/rs6497268 - AC
    OCA2 merged rs4778138/rs11855019 - AG
    OCA2 rs1800401 - AG minus, so equals TC -> mag 1; brown/black eyes more likely
    OCA2 rs1800407 - CC minus, so equals GG -> mag 1; blue/gray eyes more possible
    HERC2 (near OCA2) rs12913832 - GG -> mag 2.5; blue eye color, 99% of the time
    HERC2 rs1129038 - TT minus, so equals AA <associated to blue>

    Our kid ended up with something like grey or green. We don't know exactly. lol
    My mother-in-law. They seem blue generally, but perhaps they're actually green.

    OCA2 355 rs1800404 - CT

    OCA2 rs7495174 - AA -> blue/gray eyes more likely
    OCA2 merged rs4778241/rs6497268 - CC
    OCA2 merged rs4778138/rs11855019 - AA -> mag 1; freckles more likely
    OCA2 rs1800401 - GG minus, so equals CC -> mag 1; blue/gray eyes possible
    OCA2 rs1800407 - CC minus, so equals GG -> mag 1; blue/gray eyes more possible
    HERC2 (near OCA2) rs12913832 - GG -> mag 2.5; blue eye color, 99% of the time
    HERC2 rs1129038 - TT minus, so equals AA <associated to blue>

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    Quote Originally Posted by Regio X View Post
    One more reference: my wife. She has pure green eyes (without that little yellow).

    OCA2 355 rs1800404 - CT

    OCA2 rs7495174 - AG -> blue/gray eyes less likely
    OCA2 merged rs4778241/rs6497268 - AC
    OCA2 merged rs4778138/rs11855019 - AG
    OCA2 rs1800401 - AG minus, so equals TC -> mag 1; brown/black eyes more likely
    OCA2 rs1800407 - CC minus, so equals GG -> mag 1; blue/gray eyes more possible
    HERC2 (near OCA2) rs12913832 - GG -> mag 2.5; blue eye color, 99% of the time
    HERC2 rs1129038 - TT minus, so equals AA <associated to blue>

    Our kid ended up with something like grey or green. We don't know exactly. lol
    interesting ....................I not sure if that is the correct indicator of green eyes

    my father had Light Green eyes
    OCA2 rs1800404 28235773 .... T / T


    me , mid green eyes

    OCA2 rs1800404 28235773 .... C / T


    and both sons have blue eyes
    OCA2 rs1800404 28235773 ...... C / T


    so either 23andme is in error ............maybe as they now state that myself, father and sons all the same breakdown of 51% blue , 47% green and 2% hazel

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    sons blue eyes ........................note my father and myself are also the exact same as below ..................as studies say, green eyes come out of blue eyes

    OCA2 rs7495174 28344238 ...... A / A



    should consult

    https://www.snpedia.com/index.php/Eye_color

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    @torzio
    I'm affraid one SNP in isolation is not informative of eye color.

    Quote Originally Posted by torzio View Post
    sons blue eyes ........................note my father and myself are also the exact same as below ..................as studies say, green eyes come out of blue eyes

    OCA2 rs7495174 28344238 ...... A / A



    should consult

    https://www.snpedia.com/index.php/Eye_color
    Thanks for the link. I listed some of the most important at OCA2 and HERC2. I missed gs259 and gs260, but SNPedia says they may be of low value. Anyway...

    HERC2
    rs916977 - Mine, Father's and Mother's CT (GA); Wife's and mother-in-law's CC (GG)
    rs1667394 -
    Mine, Father's and Mother's CT (GA)
    Wife's and mother-in-law's TT (AA) -> mag 1.5; blond hair & blue eyes is 4x more likely


    Apparently, those ASIP 8818*A, OCA2 355*A and TYR 192*A are not considered that important anymore. Must be old stuff.

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    @Regio X, I have the same results as yours for:
    rs916977 CT / rs1667394 CT

    @Torzio ... same rs7495174 AA as you






    ... I went to check my eye color again, ... still castani, lol

    rs916977 15 28513364 CT
    rs1667394 15 28530182 CT
    rs7495174 15 28344238 A A

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    Quote Originally Posted by Salento View Post
    @Regio X, I have the same results as yours for:
    rs916977 CT
    rs1667394 CT
    As I posted above, these two would be of low value according to SNPedia.
    Anyway, you could post your results for all mentioned SNPs, in order to understand why after all you ended up with brown eyes.
    It seems your results for eye color could be similar to my father's. :)

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    Quote Originally Posted by Regio X View Post
    As I posted above, these two would be of low value according to SNPedia.
    Anyway, you could post your results for all mentioned SNPs, in order to understand why after all you ended up with brown eyes.
    It seems your results for eye color could be similar to my father's. :)
    I know why!

    Io so perfettamente il perché!
    mia madre ha gli occhi verdi, mio padre castani, la nonna materna celesti, il nonno materno castani.

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    The point was about the many contradictions showing in my assigned results,
    probably caused by the blue/brown/green eye mix in my family.

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    Level completed: 11%, Points required for next Level: 808
    Overall activity: 35.0%


    Country: Italy



    Quote Originally Posted by Salento View Post
    I know why!

    Io so perfettamente il perché!
    mia madre ha gli occhi verdi, mio padre castani, la nonna materna celesti, il nonno materno castani.
    Quote Originally Posted by Salento View Post
    The point was about the many contradictions showing in my assigned results,
    probably caused by the blue/brown/green eye mix in my family.
    I understand what you mean by contradiction, but there is not an actual one, as you likely know. It is, say, a matter of necessity and sufficiency. Certain SNP results/combinations may be necessary for light eyes, which doesn't mean they are sufficient.
    The "complexity" comes also from the fact eye color is a polygenic trait, reason why I haven't listed just the single OCA2 SNP that is in the table.
    The SNPs I firstly listed would have an important weight in determining eye color anyway, but it's true there must be others involved some how. The way they "interact", so to speak, doesn't seem perfectly known though, since GedMatch - and IIRC 23andMe - predicted mine wrongly. Perhaps there're some other tools available, more accurate?
    As for your parents, yep, the brown eyes of your father help to explain yours, sure, however, even brown vs. brown may result in light eyes, as you probably know, too.

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