TLRs, PAMPs, and Alley Oop

I hear that some Eurasians  – probably more than some – have Neanderthal or Denisovan versions of TLRs.  Not surprising: we’ve already seen this happen with other immune system genes – HLA variants , OAS1, STAT2  all have adaptive variants that originated with archaic humans.

TLRs   (Toll-Like Receptors) are just plain interesting, but I don’t think many people are familiar with them.  They’re part of the innate immune system:  they don’t learn from experience, as happens with the adaptive immune system (recombination,  clonal selection and all that): they just know.  Born that way.

They sense pathogens by detecting molecular patterns characteristic of major classes of pathogens that we just don’t have.  These are called PAMPs (pathogen-associated molecular patterns). They can detect  lipopolysaccharide (LPS), characteristic of gram-negative bacteria. and peptidoglycan, characteristic of gram-positive bacteria. Some detect viral-double-stranded RNA.

There are ten TLRs in humans.   Generally, they react with molecular patterns  that we don’t even have. TLR-1 recognizes bacterial lipoprotein and peptidoglycans (strep and staph), TLR-2  recognizes bacterial peptidoglycans( gram-positive bacteria)  and zymosan (fungi), TLR-3 double stranded RNA (viruses) ,  TLR-4 lipopolysaccharides (salmonella) , TLR-5 bacterial flagella (listeria) , TLR-6 bacterial lipoprotein, TLR-7 single-stranded RNA (viruses) , TLR-8 single-stranded RNA(viruses) , TLR-9 CpG DNA (bacteria) .  TLR-10 appears to play an inhibitory role, down-regulating TLR-2 .

Back in the days when vaccine development was cutting-edge, I think that people knew that the body automatically reacted to some pathogens, but it has taken a long time to discover the complex details, not that we’re quite done yet.

P.S. according to some, one factor inducing Pygmyization was the high pathogen load in dense tropical jungles.  I don’t know if that was the case, but if so, considering  that it looks as if African Pygmies (also Bushmen) admixed a bit  with a very divergent hominid population (more divergent than Neanderthals) , it wouldn’t be surprising if they picked up some immune system gene variants that helped deal with that jungle environment.

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First* Peoples

There are two new papers out on the early colonization of the Americas, one in Science and one in Nature.  The Science paper claims that all Amerindians stem from a single Siberian population that moved into Beringia about 23,000 years ago and entered America about 15,000 years ago, splitting into northern and southern branches about 13,000 years ago. They also found a touch of Australo-Melanesian ancestry among some, not all, living Amerindians – they saw it in Aleuts and the Surui ( Amazonian Indians). They concluded that this ancestry must have arrived well after the initial colonization of the New World:    “The widely scattered and differential affinity of Native Americans to the Australo-Melanesians, ranging from a strong signal in the Surui to much weaker signal in northern Amerindians such as Ojibwa, points to this gene flow occurring after the initial peopling by Native American ancestors.” In much the same way, the fact that you see widely different amount of Bushman admixture in Bantu groups  in southern Africa ( a lot in the Xhosa, almost none in some other groups) suggests that the Bushmen arrived after the Bantu,  except that it doesn’t of course.

The Nature paper concentrates on the Australo-Melanesian story: they see it mainly in the Amazon Basin,  1-2%. The  closest extant population is the Onge, pygmies of the Andaman Islands, but you see this anomalous relatedness in the Papuans, Australian Aborigines, Mamanwa (Philippine Negritos), and at lower levels in a number of groups in South Asia. In many Amerindian groups this component is much weaker or nonexistent.

The authors of the Nature paper believe that this admixture most likely happened before the settlement of the Americas, but they aren’t sure: the linkage disequilibrium says some time between 40,000 and 4,000 years ago, probably after the Ancient North  Eurasians mixed into the Amerindians. They talk about population Y, a separate movement into the Americas by a population that had probably already acquired this Australo-Melanesian component.

The background fact is that the earliest skeletons, especially in Brazil, look like Australo-Melanesians.  Long skulls.  If population Y were almost entirely standard Amerindian, with only a smidgen of Australo-Melanesian ancestry, they would have looked like Amerindians.  On the other hand, if the original settlers of the Americas were mostly or entirely Australo-Melanesian (or more exactly something vaguely related to those existing populations) they would have those long, narrow skulls.  This is the Paleoamerican model – and if true, it means that an Onge-like population arrived first, and that the incoming Amerinds almost completely wiped out them out later,  with here and there a bit of admixture.

As I understand the law, this would mean that we have to build little casinos inside the existing casinos.  For some small establishments, this might mean designating the proceeds of a single slot machine to various Amazonian tribes, or possibly to the Onge as next of kin.

* It’s complicated.

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Baby Steps

Very early settlers of North America had at least some ability to make water-crossings, since there is  there is evidence of early human activity on the Channel Islands off California (Santa Rosa, for example).  But by the time they crossed the continent and reached the Gulf Coast, those traditions had decayed and had to be re-invented: the islands of the Caribbean were not settled until several thousand years later.  There were various odd animals on some of those islands, for example ground sloths the size of a bear.  They did not go extinct at the same time as the large animals on the mainland: they waited for people to show up and then kicked the bucket.  Which is odd if you think that climate change or an impact caused those mainland extinctions.


When humans did arrive, they seem to have started in Trinidad (very close to the South American coast) and moved up the Lesser Antilles. This seems to have happened repeatedly with successive waves of invaders, the last being the Caribs.

This suggests that a chain of islands with fairly small separations is a good recipe for developing your maritime capabilities, and maybe that was the case for the road that started with Bali and continued on to Sahul and the Solomon islands, back in the day.

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Brain Topography

Although Richard Nisbett has written about long-term differences in cognitive style between East and West,  he is, I think, dismissive of the possibility that biology might explain such differences, or any other mental differences – at least publicly. He had a piece in the New York Times titled “All Brains Are the Same Color”, for example.

But as it turns out,  the three-dimensional geometry of the cortical surface is highly predictive of individuals’ genetic ancestry – there are regional differences in the folding and gyrification, as well as volume and cortical area.  I already knew that the Chinese had decided to develop their own brain anatomical atlas, due to average differences between European and  Chinese brains, but this article takes it farther.

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The Water-Crossers

Science Magazine

One interesting and puzzling question is when and how humans  developed the ability to make ocean crossings.  Although much of the Indonesian archipelago turns into a peninsula during the glacial peaks (Sundaland), it’s never possible to walk to Sahul (Australia/New Guinea). I don’t think it was ever quite possible to walk to the main Philippine islands, either. Palawan had a land connection with Borneo at times of extreme glaciation, but the last time that happened was something like four hundred thousand years ago, well before modern humans.

Homo erectus had a limited ability to cross these water barriers, as far as we can tell. They seem to have managed to get to Flores (judging from old tools and of course  hobbits) , which meant that they had to make two short sea crossings, Bali to Lombok and then Lombok to Flores. Apparently some kind of tool-maker reached Timor as well, and some other islands of Wallacea.  But none managed to get all the way to Sahul – if they had, they would have spread widely and left plenty of very old stone tools, which have not been found.

Modern humans were better at crossing water barriers: they made it to Sahul and the Philippines. The two colonizing populations were evidently related – you can see this in some of the remaining Philippine Negritos, like the Mamanwa, that also have that characteristic Denisovan admixture. These people went on to colonize the Solomon Islands about 40,000 years ago, but  didn’t go further: after the Solomons  you have to cross 200 miles of open ocean to go further, and that didn’t happen until the Polynesians arrived, relatively recently.

This is hard to square with the fact modern humans apparently couldn’t manage to settle Cyprus and some other Mediterranean islands ( judging by the late survival of their odd fauna, such as 3-foot elephants)  until just a few thousand years ago, but that’s what it looks like.

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It has long been known that inbreeding is bad for you. A new paper in Nature (Directional dominance on stature and cognition in diverse human populations) finally gives us a good quantitative estimate of just how bad it is. They find that the offspring of first cousins suffer an average reduction of  1.2 cm in height and 0.3 sd in g ( ~4.5 IQ points) .  They directly measured runs of homozygosity –  more accurate than estimating from genealogy, and better in other ways as well.  Children of first cousin marriages also suffer an elevated incidence of significant genetic disease, roughly 1.5-2 times the non-inbred risk.

That’s not all that far from my previous horseback guess.  The field was full of old and messy studies, so horseback guesses were the best you could do, until now.

The article mentions that Darwin recognized negative effects of inbreeding (a bit too late): they also say that he was among the first to do so, which is not true.  Al-Jahiz talked about it back in the Abbasid caliphate (around 800 AD) and assumed that everybody knew about it: “as the reader knows, the same is the case with horses, camels, asses and pigeons when they are inbred. ”  I suspect that people noticed this soon after farm animals were domesticated, thousands of years ago.

In some parts of the world, mainly the Middle East and North Africa, cousin marriage is very common, with tens of percent of the population practicing it.  Repeated marriages among close relatives can sometimes push the homozygosity up considerably higher than the first-cousin level, with even worse results.

Some retards (British papers) have been spinning this as saying that there are big benefits to mixed-race marriage.   Untrue: to avoid lots of ROH (runs of homozygosity), just marry someone who isn’t from the same isolated population as you. We’re talking outside the valley or across the river : intercontinental travel is not necessary.  Now there might be a degree of hybrid vigor in some distant crosses (currently unclear) – but likely not enough to compensate for someone coming from a group that has low trait values. Marry a Pygmy and your kids are going to be short.  Marry someone from a population whose average IQ  is below 90 (much of the world) and your kids will on average be less smart.

Naturally, enlightened opinion increasingly supports legalization of first-cousin marriage, due to its usual ignorance, perversity, and nihilism.

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