Neanderthal DNA–hey!–what is it good for?

Quite a bit.

First, a bit of history:

neanderthalmap
map of Neanderthal DNA in humans

It appears that there were (at least) 3 main cross-breeding events with Neanderthals. The first event most likely happened when one small band of humans had left Africa and ventured into the Middle East, where Neanderthals were living. The DNA acquired from that partnership can be found in all modern non-Africans, since they are all descended from this same group. (Since there has also been back-migration from the Middle East into Africa sometime in the past 70,000 years, many African groups also have a small amount of this DNA.)

Soon after, the group that became the Melanesians, Papuans, and Aborigines split off from the rest and headed east, where they encountered–and interbred with–the mysterious Denisovans, a third human species that we know mostly from DNA. Various sources claim this happened before the second neanderthal inter-breeding event, but just looking at the amount of admixed neanderthal in Oceanans suggests this is wrong.

Meanwhile, the rest of the non-African humans, probably still living in the Middle East or Eurasian Steppe, encountered a second band of Neanderthals, resulting in a second admixture event, shared by all Asians and Europeans, but not Melanesians &c. Then the Asians and Europeans went their separate ways, and the Asians encountered yet a third group of Neanderthals, giving them the highest rates of Neanderthal ancestry.

nature-siberian-neanderthals-17.02.16-v2

During their wanderings, some of these Asians encountered Melanesians, resulting in a little Denisovan DNA in today’s south Asians (especially Tibetans, who appear to have acquired some useful adaptations to Tibet’s high altitude from ancient Denisovans.)

There were other interbreeding events, including a much older one that left homo sapiens DNA in Neanderthals, and one that produced Denny, a Neanderthal/Denisovan hybrid. There were also interbreeding events in Africa, involving as-yet unidentified hominins. (In the human family tree to the right/above, Melanesians are included within the greater Asian clade.)

Who married whom? So far, we’ve found no evidence of Neanderthal mitochondrial DNA–passed from mothers to their children–in modern humans, so the pairings most likely involved Neanderthal men and human women. But we have also found extremely little Neanderthal DNA on the Y chromosome–so it is likely that they only had female children, or any male children they had were infertile.

Anthropogenesis-DenisovaAlleleMapInterestingly, we find higher amounts of Neanderthal DNA in older skeletons, like the 40,000 year old Tianyuan Man, or this fellow from Romania with 10% Neanderthal DNA, than in modern humans. Two potential explanations for the decrease: later mixing with groups that didn’t have Neanderthal DNA resulted in dilution, or people with more Neanderthal DNA just got out-competed by people with less.

Given the dearth of DNA on the Y chromosome and the number of diseases linked to Neanderthal DNA, including Lupus, Crohn’s, cirrhosis, and Type-2 diabetes, the fact that morphological differences between Sapiens and Neanderthals are large enough that we classify them as different species, and the fact that Neanderthals had larger craniums than Sapiens but Sapiens women attempting to give birth to hybrid children still had regular old Sapiens pelvises, gradual selection against Neanderthal DNA in humans seems likely.

However, the Neanderthals probably contributed some useful DNA that has been sorted out of the general mix and come down the ages to us. For example, the trait that allows Tibetans to live at high altitudes likely came from a Denisovan ancestor:

Researchers discovered in 2010 that Tibetans have several genes that help them use smaller amounts of oxygen efficiently, allowing them to deliver enough of it to their limbs while exercising at high altitude. Most notable is a version of a gene called EPAS1, which regulates the body’s production of hemoglobin. They were surprised, however, by how rapidly the variant of EPAS1spread—initially, they thought it spread in 3000 years through 40% of high-altitude Tibetans, which is the fastest genetic sweep ever observed in humans—and they wondered where it came from.

Modern humans have Neanderthal DNA variants for keratin (a protein found in skin, nails, hair, etc.,) and UV-light adaptations that likely helped us deal with the lower light levels found outside Africa. There’s circumstantial evidence that microcephalin D could have Neanderthal origins (it appeared about 37,000 years ago and is located primarily outside of Africa,) but no one has found microcephalin D in a Neanderthal, so this has not been proven. (And, indeed, another study has found that Neanderthal DNA tends not to be expressed in the brain.)

Yet on the other hand, Neanderthal admixture affected sapiens’ skull shapes:

Here, using MRI in a large cohort of healthy individuals of European-descent, we show that the amount of Neanderthal-originating polymorphism carried in living humans is related to cranial and brain morphology. First, as a validation of our approach, we demonstrate that a greater load of Neanderthal-derived genetic variants (higher “NeanderScore”) is associated with skull shapes resembling those of known Neanderthal cranial remains, particularly in occipital and parietal bones. Next, we demonstrate convergent NeanderScore-related findings in the brain (measured by gray- and white-matter volume, sulcal depth, and gyrification index) that localize to the visual cortex and intraparietal sulcus. This work provides insights into ancestral human neurobiology and suggests that Neanderthal-derived genetic variation is neurologically functional in the contemporary population.

(Not too surprising, given Neanderthals’ enormous craniums.)

Homo sapiens also received Neanderthal genes affecting the immune system, which were probably quite useful when encountering new pathogens outside of Africa, and genes for the “lipid catabolic process,”[19] which probably means they were eating new, fattier diets that Neanderthals were better adapted to digest.

Even Neanderthal-derived traits that today we cast as problems, like Type II Diabetes and depression, might have been beneficial to our ancestors:

“Depression risk in modern human populations is influenced by sunlight exposure, which differs between high and low latitudes, and we found enrichment of circadian clock genes near the Neanderthal alleles that contribute most to this association.”

Why would we find an association between Neanderthal DNA and circadian clock genes? Neanderthals had thousands of years more exposure to Europe’s long nights and cold winters than homo Sapiens’; it is unlikely that they developed these adaptations in order to become less well-adapted to their environment. It is more likely that Neanderthals downregulated their activity levels during the winter–to put it colloquially, they hibernated.

No problem for furry hunter-gatherers who lived in caves–much more problematic for information age workers who are expected to show up at the office at 9 am every day.

Type II diabetes affects digestion by decreasing the production of insulin, necessary for transporting converting carbs (glucose) into cells so it can be transformed into energy. However, your body can make up for a total lack of carbs via ketosis–essentially converting fats into energy.

Our hunter-gatherer ancestors–whether Neanderthal or Sapiens–didn’t eat a lot of plants during the European and Siberian winters because no a lot of plants grow during the winter. If they were lucky enough to eat at all, they ate meat and fat, like the modern Inuit and Eskimo.

And if your diet is meat and fat, then you don’t need insulin–you need ketosis and maybe some superior lipid digestion. (Incidentally, the data on ketogenic diets and type II diabetes looks pretty good.)

In sum, Neanderthal and Denisovan DNA, while not always useful, seems to have helped Homo sapiens adapt to colder winters, high altitudes, new pathogens, new foods, and maybe changed how we think and perceive the world.

 

 

Kabloona Friday

(Part of a series on de Poncins’s Kabloona, an ethnography of the Eskimo/Inuit.)

How’s winter treating you?

Up near the North Pole, I hear it gets really cold. Like, really cold:

That journey homeward in darkness was an unrelieved agony. I was cold; I was freezing; not only in the flesh, but my soul was frozen. As I sat on the swaying and creaking sled the cold became an obsession, almost an hallucination, and soon I was in a delirium of cold. … My brain had shrunk to the dimensions of a dried raisin. Stubbornly, painfully, almost maliciously, it clung to a single thought, made room for no other image: “I am cold!” I was not cold as people Outside are cold. I was not shivering. I was in the cold, dipped into a trough where the temperature was thirty degrees below zero…

During this same journey across the frozen polar sea, the Eskimo, dressed in the same clothes and just as many layers, experienced no such hypothermic delusions. Undoubtedly this is at least in part due to evolutionary adaptations that help them withstand the cold, but a few pages earlier, de Poncins had vividly (and unknowingly) described another reason the Eskimos were much warmer than he:

I do not know what the hour was, but I who had dozed off woke up. Under my eye were the three Eskimos, three silhouettes lit up from behind by the uncertain glow of a candle that threw on the walls of the igloo a mural of fantastically magnified shadows. All three men were down on the floor in the same posture… They were eating, and whether it was that the smell of the seal had been irresistible, or that the idea of the hunt had stimulated their appetites, they had embarked upon a feast. Each had a huge chunk of meat in his hands and mouth, and by the soundless flitting of their arms made immeasurably long in the shadows on the wall, I could see that even before one piece had been wholly gobbled their hands were fumbling in the basin for the next quarter. The smell in the igloo was of seal and of savages hot and gulping. …

I have seen astonishing things, in remote places and not merely in circuses. In the New Hebrides, for example, I have unpacked my own meat in a circle of cannibals and have seen in their eyes a gleam that was perhaps more intense than comforting. Here, in this igloo, all that I had seen before was now surpassed. There were three men, and there must have been fifty pounds of meat. The three men attacked that meat with the rumbling and growling of animals warning their kind away from their private prey. They ground their teeth and their jaws cracked as they ate, and they belched… The walls of the igloo were horrid with the ruddy dripping of bloody spittle and still they ate on, and still they put out simian arms and turned over with indescribable hands morsels in the beginning disdained and now become dainties greedily swallowed. And till, like beats, they picked up chunks and flung them almost instantly down again in order to put their teeth into other and perhaps more succulent bits. They had long since stopped cutting the meat with their circular knives: their teeth sufficed, and the very bones of the seal cracked and splintered in their faces. What those teeth could do, I already knew. When the cover of a gasoline drum could not be pried off with the fingers, an Eskimo would take it between his teeth and it would come easily away. When a strap made of seal skin freezes hard–and I know nothing tougher than seal skin–an Eskimo will put it in his mouth and chew it soft again. And those teeth were hardly to be called teeth. Worn down to the gums, they were sunken and unbreakable stumps of bone. If I were to fight with an Eskimo, my greatest fear would be lest he crack my skull with his teeth.

But on this evening their hands were even more fantastic than their teeth. … Their capacity of itself was fascinating to observe, and it was clear that like animals they were capable of absorbing amazing quantities of food, quite ready to take their chances with hunger a few days later.

The traditional Eskimo diet contains little to no vegetable matter, because very few plants grow up near the North Pole, especially in winter. It consists primarily of fish, seal, polar bear, foxes, and other meats, but by calorie, it is mostly fat. (This is because you can’t actually survive on a majority-protein diet.)

To run through the dietary science quickly, de Poncins has throughout the book been generally eating white-man’s food, which includes things like bread and beans. This is not to say that he disdained fish and seals–he does not make much mention of whether he ate those, but he does talk about bread, potatoes, beans, etc. So de Poncins is eating what you’d call a “normal” diet that makes use of glucose to transform food into energy. The Eskimo, by contrast, are eating the “Atkins” diet, making use of the ketogenic cycle.

No plants = no carbs; no carbs = no glucose.

But the brain cannot run without glucose, so luckily your body can make it out of protein.

Interestingly, you will die without proteins and fats in your diet, but you can survive without carbs.

Anyway, one of the side effects of a high-protein, ketogenic diet is (at least occasionally,) increased body heat:

Karst H, Steiniger J, Noack R, Steglich HD: Diet-induced thermogenesis in man: thermic effects of single proteins, carbohydrates and fats depending on their energy amount. Ann Nutr Metab 1984, 28(4):245-252.

Abstract: The diet-induced thermogenesis of 12 healthy males of normal body weight was measured by means of indirect calorimetry over 6 h after test meals of 1, 2 or 4 MJ protein (white egg, gelatin, casein), carbohydrate (starch, hydrolyzed starch) or fat (sunflower oil, butter). The effect of 1 MJ protein was at least three times as large as that of an isocaloric carbohydrate supply. [bold mine]

(isocaloric = having similar caloric values)

In other words, the Inuits’ low-carb diet probably increased their internal body temperature, keeping them warmer than our author.

I have attempted a low-carb diet, (solely for health reasons–I have never wanted to lose weight,) and one of the things I remember about it is that I would suddenly feel completely, ravenously hungry. There were times that, had I not been able to get food, I would not have begun devouring anything even remotely chewable. Of course, that may have just been a personal digestive quirk.

I feel compelled to note that this post is not advocating any particular diet; you are most likely not an Eskimo and there is no particular reason to believe, a priori, that you are better adapted to their diet than to the diet of your ancestors (whatever that happens to be.)

Unfortunately, this also holds true for the Eskimo, who probably are adapted to their ancestral diet and not adapted to the white man’s foods, which explains why diabetes and obesity are becoming epidemic among them:

Age-standardized rates of T2D show 17.2% prevalence of Type 2 Diabetes among First Nations individuals living on reserves, compared to 5.0% in the non-Aboriginal population; … First Nations women in particular suffer from diabetes, especially between ages 20–49. They have a 4 times higher incidence of diabetes than non-first nation women[3] as well as experiencing higher rates of gestational diabetes than non-Aboriginal females, 8-18% compared to 2-4%.[1]

“First nations” is Canadian for “Indian”.

In Greenland (majority Inuit):

The age-standardized prevalences of diabetes and IGT were 10.8 and 9.4% among men and 8.8 and 14.1% among women, respectively.

I am reminded here of the chapter in Dr. Price’s Nutrition and Physical Degeneration (copyright 1939) on the Eskimo (which is, alas, too long to quote in full):

During the rise and fall of historic and prehistoric cultures that have often left their monuments and arts following each other in succession in the same location, one culture, the Eskimo, living on until today, bring us a robust sample of the Stone Age people. … The Eskimo face has remained true to ancestral type to give us a living demonstration of what Nature can do in the building of a race competent to withstand for thousands of years the rigors of an Arctic climate. Like the Indian, the Eskimo thrived as long as he was not blighted by the touch of modern civilization, but with it, like all primitives, he withers and dies.

In his primitive state he has provided an example of physical excellence and dental perfection such as has seldom been excelled by any race in the past or present. … It is a sad commentary that with the coming of the white man the Eskimos and Indians are rapidly reduced both in numbers and physical excellence by the white man’s diseases. …

Bethel is the largest settlement on the Kuskokwim, and contains in addition to the white residents many visiting Eskimos from the nearby Tundra country surrounding it.

From this population, Dr. Price noted:

88 Eskimos and mixed-race people, with 2,490 teeth.

27 lived on the traditional Eskimo diet. Of their 796 teeth, one had a cavity.

21 lived on a mixed Eskimo/white diet. Of their 600 teeth, 38–6.3%–had cavities.

40 lived on imported white foods. Of their 1,094 teeth, 252–or 21.1%–had cavities.

In another location, 28 people eating a traditional Eskimo diet had one cavity.

13 people on traditional Eskimo diet: 0 cavities.

72 people on Eskimo diet: 2 cavities.

81 people eating white foods: 394 cavities.

20 people eating white foods: 175 cavities.

(Yes, Dr. Price is a dentist.)

It is a common belief around the world that childbearing makes women lose teeth (my own grandmother lost two teeth while pregnant;) Dr. Price notes the case of an Eskimo woman who had borne 20 children without losing a single tooth or developing any cavities.

One does not get a conception of the magnificent dental development of the more primitive Eskimos simply by learning that they have freedom from dental carries [cavities]. The size and strength of the mandible, the breadth of the face and the strength of the muscles of mastication all reach a degree of excellence that is seldom seen in other races. …

Much has been reported in the literature of the excessive wear of the Eskimo’s teeth, which in the case of the women has been ascribed to the chewing of the leather in the process of tanning. [de Poncins also makes note of the frequent chewing of hides–evX.] It is of interest that while many of the teeth studied gave evidence of excessive wear involving the crowns down to a depth that in many individuals would have exposed the pulps, there was in no case an open pulp chamber. They were always filled with secondary dentin.

Hey, DNA: What is it good for?

So why do we still have bits of Neanderthal DNA hanging around after so many years? Of course it could just be random junk, but it’s more fun to think that it might be useful.

And the obvious useful thing for it to do is climate adaptation, since Neanderthals had been living in dark, cold, ice-age Europe for much longer than the newly-arrived h. Sapiens, and so might have had some adaptations to help deal with it.

Okay, so here is something related I was reading the other day, that I consider pretty interesting. So it looks like the people who live up on the Tibetan Plateau (like the Tibetans,) are really well-adapted to the altitude. No mean feat, considering that other populations who live at similar altitudes don’t seem to be as well-adjusted, despite living up there for similar lengths of time.

Well, now it appears that the Tibetans have actually been living in Tibet for waaaay longer than expected, because the original h. Sapiens who moved into Tibet intermarried with archaic hominids who had already lived there for hundreds of thousands of years, and so probably picked up their altitude adaptations from those guys.

BTW, “species” is a social construct and you probably shouldn’t bother with it here.

So what kind of useful stuff might we have picked up from Neanderthals?

First I’d like to interject that I still find declarations of “aha, we got this gene from Neanderthals and it does this!” to be speculative and prone to changing. All of the articles I’ve read tend to report the same list of stuff in a similar fashion, so I suspect they’re all workign off one or two sources, which makes everything doubly sketchy. So we’re going in here with a big “if” this is true…

Some of the results are fairly boring, like Neanderthal DNA affecting hair and skin. We already speculate that skin tone helps us deal with sunlight levels, so that’s sensible.

More interesting is the claim that Neanderthal DNA may predispose people to Type-2 Diabetes and depression.

Now why the hell would it do that? It’s probably not *just* random–after all, large stretches of DNA have little to no Neanderthal admixture at all, suggesting that genes in those spots just weren’t useful, so why would we have retained such apparently negative traits?

Maybe, like sickle cell anemia, these things actually have a positive function–at least in the right environments.

I read a fascinating theory a few years ago that Type 2 Diabetes and Seasonal Affective Disorder are actually just part of our bodies’ natural mechanisms for dealing with winter. Basically, you’re supposed to eat plants and get fat all summer long, while plants are available, and then by winter, your ability to absorb more glucose shuts down (there’s no point since the plants are all dead) and you switch over to burning ketones instead and eating an all-mammoth diet.

(Some groups, like the Inuit and Masai, historically [and may today still] survived on diets that included virtually no plants and so ran all of their cellular energy needs through the ketogenic instead of the glucose system.)

During this winter time, humans, like other animals, slowed down and semi-hibernated to save energy and because why the fuck not, it’s dark and no one has invented lightbulbs, yet.

By spring, you’ve lost a lot of weight, the plants come back, and so does your ability to use glucose.

This theory is laid out in the book Lights Out by T. S. Wiley, if you’re curious. I thought it was a really interesting book, but you might just think it’s all crank, I dunno.

Anyway, a big hole in Wiley’s plot is how we actually got this adaptation in the first place, since it’s a pretty complicated one and h. Sapiens hasn’t actually been living in places with winter for all that long. Wiley just claims that it’s a deep internal mechanism that animals have, which always struck me as kinda bunk because why would a species that evolved in Africa, from other animals in Africa, etc., probably going back for million upon millions of years, have some sort of complicated system like this still functional in its genome? A trait that is not undergoing positive selective pressure is probably going to become non-functional pretty quickly. But the theory was cool enough otherwise to ignore this bit, so I’ve kept it around.

Right, so here’s the (potential) answer: h. Sapiens didn’t have this adaptation hiding deep inside of them, Neanderthals had it. Neanderthals had been living in cold places for way, way longer than h. Sapiens, and by inter-breeding with them, we got to take advantage of a bunch of cold-weather adaptations they’d developed over that time frame–thus getting a jump-start on evolving to cope with the weather.

At any rate, if Wiley is correct, and SAD and Type-2 Diabetes are actually part of a dealing with winter complex that benefited our cold-weather ancestors, then that wold explain why these genes would have persisted over the years instead of being bred out.

An easy way to test this would be to compare rates of Type-2 Diabetes and SAD among African immigrants to Europe/other wintery latitudes, African Americans (who have a small amount of Euro admixture,) and Europeans. (Watching out, of course, for Vit D issues.) If the Euros have more SAD and Type-2 Diabetes than Africans living at the same latitude, then those would appear to be adaptations to the latitude. If the Africans have more, then my theory fails.