The Unz Review: An Alternative Media Selection
A Collection of Interesting, Important, and Controversial Perspectives Largely Excluded from the American Mainstream Media
 TeasersGene Expression Blog
The Strange Tales of ABCC11 (And Your Body Odor)
🔊 Listen RSS
Email This Page to Someone

 Remember My Information



=>

Bookmark Toggle AllToCAdd to LibraryRemove from Library • BShow CommentNext New CommentNext New ReplyRead More
ReplyAgree/Disagree/Etc. More... This Commenter This Thread Hide Thread Display All Comments
AgreeDisagreeLOLTroll
These buttons register your public Agreement, Disagreement, Troll, or LOL with the selected comment. They are ONLY available to recent, frequent commenters who have saved their Name+Email using the 'Remember My Information' checkbox, and may also ONLY be used once per hour.
Ignore Commenter Follow Commenter
Search Text Case Sensitive  Exact Words  Include Comments
List of Bookmarks
Distribution of rs17822931 from HGDP

Distribution of rs17822931 from HGDP

Yoshiura, Koh-ichiro, et al. "A SNP in the ABCC11 gene is the determinant of human earwax type." Nature genetics 38.3 (2006): 324-330.

Yoshiura, Koh-ichiro, et al. “A SNP in the ABCC11 gene is the determinant of human earwax type.” Nature genetics 38.3 (2006): 324-330.

I’ve talked about rs17822931 in ABCC11 several times. The reasons are manifold. First, on many traits of interest it exhibits variation across populations in a simple Mendelian (recessive expression) manner. Second, there are suggestive variations in distribution. Third, the traits are kind of interesting without being biomedical. In other words, it’s a cool illustration of pleiotropy and human genetic variation that isn’t going to depress you. If you check out the SNPedia page you note that it is associated with variation in earwax type (wet vs. dry), body odor, and colostrum secretion. This is not the full list, and I’m moderately confident that biologists haven’t hit on all the major phenotypes that this affects variation in.

Until recently I’ve really only been interested in the population genetics of the trait. But talking with a few friends who were molecular biologists I realized I should follow up and dig deeper, and what I found was very interesting. Specifically, as it relates to body odor, which, like it or not is a phenotype of significance in the modern world. The trait happens to segregate within my family. My son is a TT genotype, because his parents are heterozygotes. That means he will exhibit less body odor as an adult. How much less?

In The Journal of Dermetological Science I found Functional characterisation of a SNP in the ABCC11 allele—Effects on axillary skin metabolism, odour generation and associated behaviours. Obviously this is not a journal I read often, but some of the tables are fascinating. The subjects were a few hundred Filipins. This is a population where the allele of interest segregates in intermediate frequencies. So there are many individuals with dry earwax as well as wet earwax, and all the associated traits.

Here are some tables I extracted*:

Mean malodour scores
5 hours 24 hours
TT 2.59 2.6
CT 3.26 3.4
CC 3.21 3.5
Genotype
TT CT CC
Uses deodorant 0.5 0.86 0.97
Does not use 0.5 0.14 0.03

I have no idea how subjective malodour scales work, but the moral is pretty straightforward. Those with the TT genotype saturate at a much lower point. This manifests in daily behavior. There is a fair amount of Japanese data that people who go to the doctor for body odor issues are much more likely to have wet earwax. This data from the Philippines illustrates that individuals with the derived genotype, TT, must be conscious enough of their lack of body odor to forgo deodorant purchases, even though I assume it is normative in the American influenced culture of the Philippines.

1-s2.0-S0923181113003058-gr1But most interesting to me are the chemical differences of the sweat of the different genotypes. They note that there were differences in Nα-3-methyl-3-hydroxy-hexanoylglutamine (HMHA-Gln), Nα-3-methyl-2-hexenoyl-glutamine (3M2H-Gln), and 3-methyl-3-sulfanyl-hexanol-cysteine-glycine between the genotypes. I don’t know much about these chemicals, except that they are “malodour conjugate precursors”. Not surprisingly there’s some difference in the microbial flora of the individuals as a function of genotype.

There have been attempts to understand the selection processes which may have shaped the distribution of the regional variation of this trait, but I’m not entirely convinced of what I’ve seen. Especially when the authors presume that earwax phenotype is in some ways causal (or at least it can give insight to causality, if that makes sense), when it may just be a developmental side effect. A consideration is that some models assume a recessive expression of the trait, which is true for body odor and earwax. But we don’t know if selection occurred that it was on these traits. Because of pleiotropy traits due to variation at a given gene may exhibit different levels of dominance, from full dominance, to additivity, to recessive expression. The target of selection may exhibit a different dominance coefficient than many of the side effect phenotypes (to give you a concrete example, the locus responsible for blue vs. non-blue eye color in Europeans exhibits some recessivity, but it is also responsible for variation in skin color where it is additive).

A 2009 paper using the HGDP data set found evidence of selection on ABCC11 using XP-EHH but not iHS. In other words, extended haplotype differences across populations, but not within them, which often imply sweeps near fixation between populations, rather than ongoing ones within them. To get a better sense of the distribution of the allele I decided to query the SNP in the 1000 Genomes Browser. I invite you to look at the data yourself. The sample sizes start to get pretty large in some of these populations. It is interesting that in West African populations the ancestral variant is nearly fixed, or totally so. The cases where it is not so can pretty easily be hypothesized as due to recent (last 10,000 years) Eurasian admixture. In Europe the frequency of the derived variant is low, on the order of ~10%, but in the Finnish sample it peaks at ~25%. This aligns with patterns in the HGDP data set. African populations tend to be fixed for the ancestral variant, C, while European populations have a low frequency of the derived variant, T, with a cline toward the northeast from the southwest (i.e., peaks in the Russians, lowest fraction in Sardinians). But, Middle Eastern samples in the HGDP data set have European proportions of T as well, though the Mozabites in North Africa do not. The South Asian samples in the HGDP have higher levels of the derived variant than Europeans, intermediate between that group and East Asians. But the 1000 Genomes data results in a thickening of the plot (and, with large sample sizes!). The Bangladeshis are at even a higher fraction than the Pakistani populations. The genotype counts are like so: 12 CC, 54 CT, TT. When I saw this I assumed it was the East Asian admixture, on the order of 10-20%, which might account for the enrichment of T in relation to Pakistan groups. But that is not correct. Here are the counts for Indian Telegus: 20 CC, 49 CT, and 33 TT. And Sri Lankan Tamils: 23 CC, 49 CT and 30 TT. Many hypotheses about the derived variant involve adaptations to cold climates in Northeast Asia. This may still be the case in Northeast Asia, but what you see here is a NW to SE cline of ancestral to derived variant of ABCC11 in South Asia. The Punjabis and Gujaratis have higher fractions of the ancestral variant, as you’d except from the HGDP data.** (the fraction in the Bangladeshi sample might be elevated by East Asian admixture)

The results form East Asian samples in the 1000 Genomes is also illuminating. With sample sizes of around 200 each the Dai minority (related to the Tai people culturally as their antecedents) has a frequency of 56% for T, the Han from Beijing have 97%, the Han from South China are at 86%, the Japanese 88%, and the Vietnamese from the southern region of the country 64%. First, my intuition is that this seems a strange pattern for a allele which was selected on a recessive trait. Rather, it looks more likely for selection on a dominant trait, where the equilibrium frequency remains below 100% because of recessive expression of the unfavored state. Second, the fraction for the Dai seems rather high for the ancestral state. This particular population is sampled from the Mekong region of southern China, as far south as you can go in the nation. This sort of cline correlated with latitude goes a long way to explaining why the thesis often emerged that this variation is somehow related to climate (there is something of a north-south cline in Japan as well).

Where does this leave us? I honestly don’t think we can make a general conclusion about the nature of selection around this variation. To me it looks as it was functionally constrained in Africa. African populations have the derived variant, but those that do can be explained via recent Eurasian admixture pretty easily (e.g., the LWK sample are Kenyan Bantus who have mixed with Nilotic peoples, who do have Eurasian ancestry. The same for the samples from Gambia or Senegal in relation to Eurasian mixed Fula). But once you leave Africa it look as if the constraint was removed, and lots of populations have low frequencies of the derived nonsynonymous mutation. The 2006 paper which focused in on the SNP of interest had Oceanian samples, and the derived variant fraction is too high to simply be a matter of Austronesian admixture. Could it be some form of balancing selection outside of Africa? Who knows. It might be neutral in some areas, under positive selection in others, balanced in a few locations, and under constraint in Africa.

But despite the evolutionary enigma of this locus, the phenotypic correlations keep building up. It’s a classical genetics illustration because of its Mendelian character. In terms of morphology I should emphasize that the body odor related information probably relates to the apocrine glands, which are localized in the armpits and genitals, and also are precursors to mammary secretion glands. Someone who understands these sorts of pathways and how they influence development could probably say much more. I’m sure at some point we’ll be able to answer the big evolutionary questions about this locus, and how it relates to human biological variation, but that will probably necessitate a better catalog of its phenotypic consequences.

Addendum: If you have a 23andMe account, here is the link that will show you your genotype (and anyone else on your account): https://www.23andme.com/you/explorer/snp/?snp_name=Rs17822931 (be logged in ahead of time).

* I flipped the strand, so converted T to A and G to C.

** To be fair, there was some evidence from Tamils in earlier studies, but two South Indian populations in the 1000 Genomes with high sample sizes nails it.

 
Hide 19 CommentsLeave a Comment
Commenters to Ignore...to FollowEndorsed Only
Trim Comments?
  1. It’s essentially impossible for selection to favor a pure recessive trait. You’re never going to see it. Therefore, we can conclude that some effect of this mutation shows up in heterozygotes and is favored by natural selection – but nobody seems to know what it is.

    The derived mutation reduces or eliminates colostrum production, but you’d think that would be a bad thing.

    • Replies: @RCB
    I would say *nearly* impossible: if it arose in small/inbred groups (during founder events?), then some homozygote recessives would have shown up, allowing for selection to act. Also a mutant allele might get off the ground from drift alone - especially in a growing population (probability of survival = 2r). But that would probably take too long. Not sure if either scenario is realistic.
    , @notanon

    The derived mutation reduces or eliminates colostrum production, but you’d think that would be a bad thing.
     
    Stop it completely or slow it down / spread it out for longer?
    , @Anonymous
    Sexual selection for smelling better? CT beats CC.
    , @Tom Bri
    Odd, except for the link that Razib gave above, Google can't find anything related to lower colostrum production in Asian women, at least not on the first couple pages of results. It is also not mentioned in my textbooks.
  2. i’m a CT but use deodorant minimally. i like the direct link to that SNP – usually i have no idea what’s going on concerning popgen stuff so that made it easier to relate to.

  3. OT but do you think that this could affect other areas of the brain’s development ?

    http://news.slashdot.org/story/14/11/29/1825237/finland-dumps-handwriting-in-favor-of-typing?sbsrc=md

  4. “Malodour conjugate precursors” is a good one, reminds me of the unusual substance in asparagus that is metabolized to a smelly substance that comes out in the urine. The molecules pictured here are ones that I would not expect to have much of a smell on their own, but I can understand how differing levels in sweat would affect the makeup of skin and underarm flora — as well as susceptibility to bug bites.

  5. In group SDs for each genotype (for malodour) would’ve been interesting, to give a handle on the magnitude of effect.

    “Differences in the presence of key odourants responsible for axillary malodour across the three genotypes help to explain previous general observations that certain Asian populations tend to exhibit a slightly acidic/cheesy axillary odour, compared to a more intense meaty/oniony smell proposed to originate from individuals of a more Western origin” Slightly odd paragraph.

  6. @gcochran
    It's essentially impossible for selection to favor a pure recessive trait. You're never going to see it. Therefore, we can conclude that some effect of this mutation shows up in heterozygotes and is favored by natural selection - but nobody seems to know what it is.

    The derived mutation reduces or eliminates colostrum production, but you'd think that would be a bad thing.

    I would say *nearly* impossible: if it arose in small/inbred groups (during founder events?), then some homozygote recessives would have shown up, allowing for selection to act. Also a mutant allele might get off the ground from drift alone – especially in a growing population (probability of survival = 2r). But that would probably take too long. Not sure if either scenario is realistic.

    • Replies: @gcochran
    Possible, but quite unlikely. It must have happened when chromosome numbers changed, but I can't think of a plausible example in terms of a known sweeping allele in humans or domesticated animals. Although maybe someone has deliberately selected fora recessive trait in some domesticate?
  7. @gcochran
    It's essentially impossible for selection to favor a pure recessive trait. You're never going to see it. Therefore, we can conclude that some effect of this mutation shows up in heterozygotes and is favored by natural selection - but nobody seems to know what it is.

    The derived mutation reduces or eliminates colostrum production, but you'd think that would be a bad thing.

    The derived mutation reduces or eliminates colostrum production, but you’d think that would be a bad thing.

    Stop it completely or slow it down / spread it out for longer?

  8. @RCB
    I would say *nearly* impossible: if it arose in small/inbred groups (during founder events?), then some homozygote recessives would have shown up, allowing for selection to act. Also a mutant allele might get off the ground from drift alone - especially in a growing population (probability of survival = 2r). But that would probably take too long. Not sure if either scenario is realistic.

    Possible, but quite unlikely. It must have happened when chromosome numbers changed, but I can’t think of a plausible example in terms of a known sweeping allele in humans or domesticated animals. Although maybe someone has deliberately selected fora recessive trait in some domesticate?

  9. Thanks for this. I tested as TT. Curiously, I also have dry ear wax. Nothing particular has shown up in my ancestry to explain why. I also have very sparse body hair. I recall being acutely embarrassed when I went through puberty and did not turn out to be hairy, unlike all the other guys. I have since had cause to be grateful for my relatively hairless condition, however, as when my Chinese mother-in-law said “Oh well, at least he’s not one of those hairy foreigners. And he doesn’t smell either.” (What luck – a foreign son-in-law who doesn’t stink.)

    As a self-conscious teenager, I started using underarm deodorant when I started dating girls at 16, just on the assumption that I would need it like everyone else, but stopped again when I realised there was no point and I was just wasting money on something I didn’t need.

    My daughter also tested TT (not surprising, as my wife is Chinese), tried using deodorant twice and then scrapped it because she couldn’t see any point. My wife never got tested, but I can guess in her case, because she never smells, and never uses deodorant because she never needs it. She instructed our daughter to use it, assuming she would need it as a half-foreigner, but as it turns out, she doesn’t, because her father is a foreigner of the rare stinkless variety.

    • Replies: @Karl Zimmerman
    As I posted last year, I'm very similar to you. TT, dry earwax, and no notable body odor. Also only used deodorant for a short period in high school before I realized it was basically useless.

    That said, I can use personal anecdote to say being TT absolutely does not mean you can't be hairy. On a scale of 1-10, I'm probably an 8 in terms of body hair. I'm not one of those guys who looks like he's wearing a black leather jacket when he has his shirt off. But besides my sides and the lower half of my back, there aren't too many areas of my body that don't have at least a dusting of hair.

    I do wonder if being TT had something to do with my having clear skin as a teenager though. Despite both my parents being crater-faced as adolescents, I was one of those kids who rarely had more than one pimple at a time. That said, the small amount of information I can find online suggests Asians, if anything, have more acne than whites, so it's probably just a coincidence.
  10. Anonymous • Disclaimer says: • Website

    The 2006 paper which focused in on the SNP of interest had Oceanian samples, and the derived variant fraction is too high to simply be a matter of Austronesian admixture.

    Recent East Asian admixture clearly can’t account for the derived freqs in South India — but not sure this is also true of Oceania.

    This paper’s 0.171 A Papuan sample isn’t HGDP (East Sepik) but evidently from Morobe (“Waffa”). This is exactly where Austronesian speakers, rolling upriver through the broad depression of the Markham Valley, reach their furthest inland extent on the PNG side of the island.

    Compare with the Dani from the Central Highlands here.

  11. @gcochran
    It's essentially impossible for selection to favor a pure recessive trait. You're never going to see it. Therefore, we can conclude that some effect of this mutation shows up in heterozygotes and is favored by natural selection - but nobody seems to know what it is.

    The derived mutation reduces or eliminates colostrum production, but you'd think that would be a bad thing.

    Sexual selection for smelling better? CT beats CC.

  12. The way I explained it to my daughter – she said “Who are those people who, when they get in the elevator, their smell hits you like a brick wall?” ‘They’re the CC people.”

  13. @gcochran
    It's essentially impossible for selection to favor a pure recessive trait. You're never going to see it. Therefore, we can conclude that some effect of this mutation shows up in heterozygotes and is favored by natural selection - but nobody seems to know what it is.

    The derived mutation reduces or eliminates colostrum production, but you'd think that would be a bad thing.

    Odd, except for the link that Razib gave above, Google can’t find anything related to lower colostrum production in Asian women, at least not on the first couple pages of results. It is also not mentioned in my textbooks.

    • Replies: @Sandgroper
    It's true though.

    It's well known to human breast milk researchers that there are quite big differences between European and East Asian milk.
  14. @Sandgroper
    Thanks for this. I tested as TT. Curiously, I also have dry ear wax. Nothing particular has shown up in my ancestry to explain why. I also have very sparse body hair. I recall being acutely embarrassed when I went through puberty and did not turn out to be hairy, unlike all the other guys. I have since had cause to be grateful for my relatively hairless condition, however, as when my Chinese mother-in-law said "Oh well, at least he's not one of those hairy foreigners. And he doesn't smell either." (What luck - a foreign son-in-law who doesn't stink.)

    As a self-conscious teenager, I started using underarm deodorant when I started dating girls at 16, just on the assumption that I would need it like everyone else, but stopped again when I realised there was no point and I was just wasting money on something I didn't need.

    My daughter also tested TT (not surprising, as my wife is Chinese), tried using deodorant twice and then scrapped it because she couldn't see any point. My wife never got tested, but I can guess in her case, because she never smells, and never uses deodorant because she never needs it. She instructed our daughter to use it, assuming she would need it as a half-foreigner, but as it turns out, she doesn't, because her father is a foreigner of the rare stinkless variety.

    As I posted last year, I’m very similar to you. TT, dry earwax, and no notable body odor. Also only used deodorant for a short period in high school before I realized it was basically useless.

    That said, I can use personal anecdote to say being TT absolutely does not mean you can’t be hairy. On a scale of 1-10, I’m probably an 8 in terms of body hair. I’m not one of those guys who looks like he’s wearing a black leather jacket when he has his shirt off. But besides my sides and the lower half of my back, there aren’t too many areas of my body that don’t have at least a dusting of hair.

    I do wonder if being TT had something to do with my having clear skin as a teenager though. Despite both my parents being crater-faced as adolescents, I was one of those kids who rarely had more than one pimple at a time. That said, the small amount of information I can find online suggests Asians, if anything, have more acne than whites, so it’s probably just a coincidence.

    • Replies: @Sandgroper
    I never had more than the occasional pimple. My daughter is the same. My wife - I don't think she ever had a single pimple.
    , @Ebizur
    East Asians tend to have visibly oilier skin than Europeans. I recall having been creeped out by my classmates at a non-coed high school in Japan who would wipe their faces with "aburatorigami" (oil-removing tissues) several times a day because their faces would otherwise shine with oil. Why they should be so worried about their faces looking too oily while at an all-boys school is a question for another day, though. (笑)

    However, I'm not sure that it is healthy to remove the oil that is naturally produced by the skin. It did not appear to reduce the rate of acne at least.
  15. @Karl Zimmerman
    As I posted last year, I'm very similar to you. TT, dry earwax, and no notable body odor. Also only used deodorant for a short period in high school before I realized it was basically useless.

    That said, I can use personal anecdote to say being TT absolutely does not mean you can't be hairy. On a scale of 1-10, I'm probably an 8 in terms of body hair. I'm not one of those guys who looks like he's wearing a black leather jacket when he has his shirt off. But besides my sides and the lower half of my back, there aren't too many areas of my body that don't have at least a dusting of hair.

    I do wonder if being TT had something to do with my having clear skin as a teenager though. Despite both my parents being crater-faced as adolescents, I was one of those kids who rarely had more than one pimple at a time. That said, the small amount of information I can find online suggests Asians, if anything, have more acne than whites, so it's probably just a coincidence.

    I never had more than the occasional pimple. My daughter is the same. My wife – I don’t think she ever had a single pimple.

  16. @Tom Bri
    Odd, except for the link that Razib gave above, Google can't find anything related to lower colostrum production in Asian women, at least not on the first couple pages of results. It is also not mentioned in my textbooks.

    It’s true though.

    It’s well known to human breast milk researchers that there are quite big differences between European and East Asian milk.

    • Replies: @Tom Bri
    Interesting, and weird, considering all of the much-touted benefits of colostrum. Must be something else going on. Perhaps Asians simply have a longer, slower release?
    Do you have any links I could look at?
  17. @Sandgroper
    It's true though.

    It's well known to human breast milk researchers that there are quite big differences between European and East Asian milk.

    Interesting, and weird, considering all of the much-touted benefits of colostrum. Must be something else going on. Perhaps Asians simply have a longer, slower release?
    Do you have any links I could look at?

    • Replies: @Sandgroper
    Tom, it was covered some time back when people were discussing the EDAR variant.

    Plus I am quoting my daughter, who has done some lab research on human milk, who said she had to segregate data from samples donated by Europid and Chinese donors, because of the known compositional differences. She didn't give me any refs, but was in a position to opine because she was in the game, so to speak.

    She's now no longer in the human milk business, she's opted to become a mouse killer instead.
  18. @Tom Bri
    Interesting, and weird, considering all of the much-touted benefits of colostrum. Must be something else going on. Perhaps Asians simply have a longer, slower release?
    Do you have any links I could look at?

    Tom, it was covered some time back when people were discussing the EDAR variant.

    Plus I am quoting my daughter, who has done some lab research on human milk, who said she had to segregate data from samples donated by Europid and Chinese donors, because of the known compositional differences. She didn’t give me any refs, but was in a position to opine because she was in the game, so to speak.

    She’s now no longer in the human milk business, she’s opted to become a mouse killer instead.

  19. @Karl Zimmerman
    As I posted last year, I'm very similar to you. TT, dry earwax, and no notable body odor. Also only used deodorant for a short period in high school before I realized it was basically useless.

    That said, I can use personal anecdote to say being TT absolutely does not mean you can't be hairy. On a scale of 1-10, I'm probably an 8 in terms of body hair. I'm not one of those guys who looks like he's wearing a black leather jacket when he has his shirt off. But besides my sides and the lower half of my back, there aren't too many areas of my body that don't have at least a dusting of hair.

    I do wonder if being TT had something to do with my having clear skin as a teenager though. Despite both my parents being crater-faced as adolescents, I was one of those kids who rarely had more than one pimple at a time. That said, the small amount of information I can find online suggests Asians, if anything, have more acne than whites, so it's probably just a coincidence.

    East Asians tend to have visibly oilier skin than Europeans. I recall having been creeped out by my classmates at a non-coed high school in Japan who would wipe their faces with “aburatorigami” (oil-removing tissues) several times a day because their faces would otherwise shine with oil. Why they should be so worried about their faces looking too oily while at an all-boys school is a question for another day, though. (笑)

    However, I’m not sure that it is healthy to remove the oil that is naturally produced by the skin. It did not appear to reduce the rate of acne at least.

Comments are closed.

Subscribe to All Razib Khan Comments via RSS