Did Mexicans Inherit Diabetes Risk from Neanderthals?
These days Neanderthals seem to pop up where you least expect them. When Medscape asked me a few days ago to write up a paper being published in the December 25 online Nature, the title sounded run of the mill: “Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.”
Yawn. Another genome-wide association study (GWAS), showing stretches of single sites in the genome (SNPs) that track with type 2 diabetes in Mexicans and other Latin Americans, who have about twice the prevalence as European whites. I might have been more alert had I read the ending first, like I sometimes do with novels – a “Neanderthal analysis team” that included Svante Paabo. The Neanderthal connection is also not in the headline for the news release accompanying publication of the paper, but is buried a few paragraphs down. So I wondered, on Christmas day, would the media notice the missing link? If they don’t, here’s DNA Science blog’s take.
The study is terrific, with nice numbers — 9.2 million SNPs analyzed for 3,848 Mexicans and other Latin Americans who have type 2 diabetes and 4,366 who don’t. The researchers are a stellar team from Mexico, Boston, LA and others part of the The Slim Initiative in Genomic Medicine for the Americas (SIGMA) Type 2 Diabetes Consortium.
The findings zeroed in on five linked SNPs — a haplotype — in a gene called SLC16A11 on the short arm of chromosome 17. Four of the five mutations change an amino acid in the encoded protein, and the fifth is silent. The protein normally ferries certain lipids into liver cells, a complex function that makes sense in terms of past studies of insulin resistance. The association between the haplotype and disease risk is strong, and holds up in other populations. Perhaps it could be developed into a tool to predict elevated diabetes risk, or present a new drug target in lipid metabolism. So far, so good.
But it was the DNA sequence that grabbed my full attention, and the clues from geographic prevalence.
The five-site haplotype is in 50% of Native Americans, in about 10% of East Asians, much rarer in Europeans, and absent among Africans. And it’s ancient. Researchers determine the degree to which a mutant gene differs from the most common sequence (wild type), then impose a time scale in the form of known mutation rates. The SLC16A11 five-site haplotype is so divergent that it goes back to nearly 800,000 years ago — before our ancestors expanded out of Africa.
The most plausible explanation, unexpected I suspect, seemed to be that the haplotype came from an archaic human – a Neanderthal or Denisovan or their as-yet unnamed contemporaries. And the haplotype indeed shows up in the skeleton of a Neanderthal found in the Denisovan cave in Siberia — that’s the now-famous place where the genomes that led to us sorted themselves out. It is a peek into a sometimes promiscuous past.
Having a bit of one’s genome from a Neanderthal that predisposes to diabetes might be unexpected, but the presence of this DNA source shouldn’t be stigmatizing – from 1 to 4 percent of many of our genomes are from Neanderthals (sub-Saharan Africans have none). But for a disease population so scrutinized — note the Pima Indian investigations — it’s surprising to find that a risk gene for diabetes traces back to this side branch from the evolutionary road leading to humanity.
I was going to take a blogging break until this paper appeared — next week I’ll return to the genetic stories of the Amish.
Wow what a racist title, just proves white people are racist by birth. With ur ph.d didnt they teach that Latina are a mixed race?
Get over yourself and your overinflated fragile ego.
Is this comment addressed to me? Can you please explain the context?
Don’t shoot the messenger — I am summarizing a report about a Neanderthal gene variant in the Mexican population using the language from the scientific paper. You need to read beyond the headline, which is accurate.
It is scientific research. Get a life and get over it.
[…] Did Mexicans Inherit Diabetes Risk from Neanderthals? by DNA Science Blog, unless otherwise expressly stated, is licensed under a Creative Commons […]
Really interesting. I have long suspected I, like many Americans, am of mixed race; having (I speculate) some American Indian blood on my mother’s side. This is based on coloration, predominately; since my mother, now dead, would have hotly denied any such antecedents.
Indeed, Mexicans are quite mixed. How much European blood (mestizos) do these subjects have ? Those details should be specified in order that it can be replicated, proven, or disproved.
The story goes back farther than modern races, that’s what was so surprising.
The Stellar Group? So brilliant to point out the unfortunate effects of poverty and cheap, unhealthy food. I hope I never have to lose access to clean water. The saddest part of these articles is the comments from people who are “mixed”. I’m sure the Pima Indians are not genetically inferior to any of the rest of us “mixed breeds” of humans, perhaps more drought tolerant? Native food like people are changing in many ways not for the better. Obesity is obvious to all of us.
I agree. This is science.
Obesity, poverty, unhealthy food — yes, these are important contemporary issues that are somewhat obvious. My post was about the non-obvious — a complex (5 SNP) gene variant predisposing to diabetes that came into the line leading to modern human genomes from Neanderthals. That’s nearly 800,000 years ago — which the person accusing me of not understanding the concept of mixed races just didn’t get. Perhaps the gene variant is evidence for the thrifty gene hypothesis — that very long ago, altered glucose metabolism and obesity were adaptive, enabling people (or pre-people) to survive regular, long famines. Persisting gene variants that made this possible in today’s world are no longer adaptive, but harmful. One question now is why those particular gene variants persisted. What has been the role of natural selection in keeping them around?
[…] Did Mexicans Inherit Diabetes Risk from Neanderthals? | DNA … https://blogs.plos.org/dnascience/Did Neanderthals give some of us increased risk for type 2 diabetes? (credit: Knut Finstermeier). These days Neanderthals seem to pop up where you least expect them. When Medscape asked me a few days ago to write up a … […]
I’m always a bit skeptical of GWAS’ of largely environmentally induced diseases, like T2DM. It’s really hard to justify the control group that’s used, unless they chose individuals of the same BMI/relative adiposity that didn’t have diabetes. The more interesting GWAS would be taking individuals with greater visceral/trunk adiposity that haven’t developed (pre)diabetes, to identify alleles/haplotypes that might be protective against diabetes.
-Kevin, Nutritional Sciences Graduate Student
You’re very right, your article does go into more detail. However, you can’t guarantee that everyone is going to read the whole article. I can see the scientific interest here, and I get what you’re driving at, but it’s not just about what the scientifically literate read it as saying, or what you read it as saying…it’s what all your readers will interpret as they read (or don’t read).
I thought the same thing as the original poster. With Caucasians’ history of equating non-whites with “primitive” and “savage” natures, is it really necessary to further suggest that Mexicans are any more “Neanderthal” than anyone else? Since the findings do not really affect only Mexicans, but any person who has this haplotype, couldn’t “Did Some of Us Inherit Diabetes Risk from Neanderthals?” be used instead and be potentially less offensive?
Also….”I’d love to have been a fly on the wall of the Denisovan cave, watching archaic humans swap DNA.”? …isn’t this just a BIT sexually suggestive for a professional science blog?
Wow, today serious publications gone down !!, It’s a bad conclusion about Neardenthal gene give some mexican population the diabetes type 2 risk. What about Neardenthal chromosomes ? who gave them that mutations ?? Is it not posible that those mutation can be done by others factors ??? Or can be more recents mutations also ? This article lacks of investigation.
Natural selection ? not apply in the case of recent humans. I you call natural selection why a men and a women decided live together and reproduce them is ok, but that is not the classical definition…..
Latino is not a race. Latino is not an ethnic group. Each Latin America country have a different ethnic composition. There are full blood Caucasian Latinos, full blood African descend Latinos, there are full blood Asian Latinos, etc. and also the mixture of part of all of the above.
Gisele Bundchen and Xuxa are Brazilians of German ancestry, Pele is a Brazilian of African ancestry, ex president Fujimori is a Peruvian of Japanese ancestry, Christian Meier is a Peruvian of German and Swedish ancestry, President Ollanta M Humala of Peru is a mestizo (mix Indian/European) of Inca-Italian ancestry, Pope Francis is an argentine of Italian ancestry, ex President Kirchner of Argentina was of German and Serbian ancestry, Anthony Queen Mexican actor was of Indian and Irish ancestry, Che Guevara was an Argentinean of Irish and Basque ancestry. Latinos come in all colors, creeds, ethnicities and races.
Me, you are also confused. Latino is not a race. Latino is not an ethnic group. Each Latin America country have a different ethnic composition. There are full blood Caucasian Latinos, full blood African descend Latinos, there are full blood Asian Latinos, etc. and also the mixture of part of all of the above.
Gisele Bundchen and Xuxa are Brazilians of German ancestry, Pele is a Brazilian of African ancestry, ex president Fujimori is a Peruvian of Japanese ancestry, Christian Meier is a Peruvian of German and Swedish ancestry, President Ollanta M Humala of Peru is a mestizo (mix Indian/European) of Inca-Italian ancestry, Pope Francis is an argentine of Italian ancestry, ex President Kirchner of Argentina was of German and Serbian ancestry, Anthony Queen Mexican actor was of Indian and Irish ancestry, Che Guevara was an Argentinean of Irish and Basque ancestry. Latinos come in all colors, creeds, ethnicities and races.
Rick Lewis, you are right! Latinos of Indian (native) ancestry, as well as American of Indian (native) ancestry, have a high % of diabetes. However, Latino is not an homogeneous group.
Latino is not a race. Latino is not an ethnic group. Each Latin America country has a different ethnic composition. There are full blood Caucasian Latinos, full blood African descend Latinos, there are full blood Asian Latinos, etc. and also the mixture of part of all of the above.
Gisele Bundchen and Xuxa are Brazilians of German ancestry, Pele is a Brazilian of African ancestry, ex president Fujimori is a Peruvian of Japanese ancestry, Christian Meier is a Peruvian of German and Swedish ancestry, President Ollanta M Humala of Peru is a mestizo (mix Indian/European) of Inca-Italian ancestry, Pope Francis is an argentine of Italian ancestry, ex President Kirchner of Argentina was of German and Serbian ancestry, Anthony Queen Mexican actor was of Indian and Irish ancestry, Che Guevara was an Argentinean of Irish and Basque ancestry. Latinos come in all colors, creeds, ethnicities and races.
Indians of the Americas (North/Central/South), inherited neanderthal genes. There are high sequencies of Neanderthal alleles among indians of North/Central/South American Indians. Unexpectelly, there are also Denisovan allelles in South American Indians. There were no Neanderthals or Denisovans in the Americas, but were brought from Asia.
In South America, there is also a high percentaje of Europeans of Spanish ancestry, but also German, Irish, Portuguese and Italian.
Maria, thank you so much for your several enlightening posts, you’ve really helped with the confusion about the blog post. I used the term “Mexican” because that is what the authors of the paper I was reviewing used. To change the word for reasons of political correctness would have introduced inaccuracy and oversimplification. And I honestly did not think it would offend anyone. I live in a part of the country where there aren’t very many people from Latin America, and to me, “Mexican” means simply person of Mexican heritage or someone who comes from Mexico. Thanks again!
I can see why “natural selection” might sound like a man and woman selecting each other as partners, but it has a different meaning in biology.We can see the effects of natural selection in modern day populations. It is a term that applies to any population. If a gene variant has persisted to such high prevalence, then it must confer some advantageous trait, or be linked to a gene that does (be on the same chromosome, nearby).
Yes, what you suggest would be a great experiment. The controls were people from the same populations who did not have diabetes, but at least in the version of the paper in Nature, it didn’t specify BMI. I’m particularly interested in this because one of my daughters had T2DM as a child and had I known sooner, I would have given her very different foods. That is how this finding, which I realize has insulted some people, can ultimately be quite useful. If I’d known she had a gene variant that was so powerfully connected to glucose metabolism, I would have used that information, even if it came from an australopithecine.
The conclusion from the paper reflects the data — it isn’t good or bad. Sorry you didn’t like my post. I try to find interesting new papers and provide perspective — usually not investigation. I have to fit it in with my regular work. Investigative journalism takes a great deal of time.
I was attempting to inform, not offend. If I used an “anyone can have this gene” approach — which is true — I would not be reporting on this particular paper. It would change the data to do so. This blog is about science. Of the populations studied so far, the prevalence of the haplotype is indeed higher in those of Mexican ancestry than in others. Diabetes is a big problem for people who have Mexican ancestry (which I know is very mixed), and finding such a haplotype could be very very helpful, ultimately, in preventing disease.
Swapping DNA and sex are practically synonymous with genetics — in this case, population genetics. I’d very much like to know how all of those fascinating groups of people and pre-people who left behind finger bones and skull bits in the very same cave over a vast period of time were related, and what remnants of those genomes persist today in different population groups. That’s not suggestive; it’s biology, in the informal language of a blog post. (I consider my professional writing to be books and articles, for which I am paid.)
It is great when people respond and a discussion starts. But occasionally terms that are commonly used in science have different meanings in a popular sense, and that is when people can take offense, or pass judgment on a study’s results. I’m sorry this has happened, but not sorry that I wrote about this paper. It is important and will help people. Except for those who trace their ancestry to sub-Saharan Africa, we’re all a little bit Neanderthal. That is not a value judgment — it’s biology.
>(I consider my professional writing to be books and articles, for which I am paid.)
Fair enough. I forget how many science bloggers do this for free.
I recognize what you intended. I don’t have an issue with the data or the paper’s results. Data are data. But I still think that alternate wording of the title could be just as accurate and potentially less problematic. You can take that for the random reader opinion that it is.
I’m a scientist who writes for a lay audience, as well, so I’m very aware of the issues with popular interpretations of word choice, framing, etc. I don’t write in a vacuum, and readers are from a variety of backgrounds. Taking that into consideration when choosing wording isn’t so much “political correctness” as it is just acknowledging that not everyone is like me and that they might have concerns that are just as valid, even if I don’t share them.
The public isn’t necessarily going to interpret my phrasing in the way it was intended, whether it’s technically correct or not. If I’d written something that a reader honestly thought was problematic, I’d want to know. That’s the only reason I said something.
I’ll be interested to studies looking at the relative risk that these gene variants convey, though the alleles they’re identifying seem to be involved in a plausible mechanism. Having worked in the clinic and seeing individuals with diabetes from extremely diverse ethnic backgrounds, these alleles likely lead to an earlier onset for T2DM, but only in an environment with excess calories/glucose – very rare to see individuals who truly stick to the medical nutrition therapy and normalize their BMI’s that don’t see a (near complete) reversal of the disease. From a clinical standpoint, I see some of the implications of these studies as a bit worrisome because I’ve run into patients who swear up and down that their T2DM is genetic and don’t do much to change their diets – the public (and even some MDs) seems to have a hard time differentiating between causation and susceptibility.
Thanks so much for your comments — I’m responding to “R” about my post’s insensitivity — I can’t quite figure out how to respond directly to a particular comment. I’ll try to be more sensitive in the future, and add the questionable term here to my list of topics to stay away from. I honestly thought I was covering a fascinating paper that was published on the slowest of all news days. Again, I apologize to anyone who was offended, it was certainly not intended.
I was not offended! I really liked your article.
In addition to have neanderthal genes, some South American Indians, have denisovans genes. So, I guess there were more ancient migrations, that we thought.
Sorry for my English, is second language for me. By the way, I am a South American of full irish ancestry in both sides ! Very proud of my latina culture, and very proud of my Irish ancestry.
I basically aggree with “Me”, although I wouldn’t have gone so far as to call you “racist”.
My feeling (I’m not a scientist), is that for a science paper it was an extremely poor choice of words. The title says “Mexicans”, then this is expanded to “Mexicans and Latin Americans”, then to “Native Americans” as well. No mention of any of the blood types that don’t even fit into the standard blood typing system (which would be extremely fascinating, imho).
One of my great-great-grandmothers died fairly young (67), and my great-grandmother (her daughter) didn’t do any better. My great-great-grandfather lived to about 94, probably because he wasn’t trusted. I believe you can see the significance of all this.
One of the cognitive biases that I see in academia is the belief that history began with the invention of writing. I think this belief is seriously damaging scientific inquiry, and reinforcing European’s belief in racial superiority.
I’d like to note for the record that I believe it’s important to disuss such issues for the good of all concerned, for minorities as well as for the scientists. Thank you for your patience and understanding.
Btw, I could throw you a bone about history, but I’m not ready to discuss it publicly, sorry.
One of the problems with majoring in biology, at least when I did, was that the required science and math courses left hardly any time for anything else — so I know a lot about genetics, but not much about everything else. Graduate school just became narrower and narrower. Looking back, I’d like to trade some of the physics and zoology perhaps for art history or music. I guess that’s what retirement is for — catching up and expanding.
What I don’t understand is if Mexicans (I myself am Mexican) inherited the diabetes genome from Neanderthals through the Asian population that migrated to the Americas tens of thousands of years ago through Homo Sapiens interbreeding with Neanderthals, how is it that Europeans didn’t since they also have Neanderthal genomes?