Wednesday, April 09, 2014

The essential difference

This is a recent talk at NIH, which contains some unpublished results.

In the final part of the talk (you can skip there via this link), Paabo discusses the genetic variants (~30k SNPs) that are fixed in essentially all modern humans, but are not present in the Neanderthal genomes sequenced thus far. These variants are presumably responsible for the differences between Neanderthals and moderns. Paabo obviously believes that enhanced cognition is one of the main differences, and he discusses the archaeological evidence for this. He also discusses functional investigations in genetically engineered mice, and advocates for large GWAS that might identify rare humans with "back-mutations" to the Neanderthal variant. Such studies could identify phenotypical effects.

In his recent book, Paabo wrote
(p.213) ... we estimated that the total number of DNA sequence positions at which Neanderthals differed from all humans living today will be on the order of 100,000. This will represent an essentially complete answer to the question of what makes modern humans "modern," ...

(p.253) [last paragraph of the book!] ... One can imagine putting such changes into cell lines, and into mice [or monkeys] ... in order to "humanize" or "neanderthalize" biochemical pathways or intracellular structures ... One day, we may understand what set the replacement crowd [moderns] apart from their archaic contemporaries, and why, of all the primates, modern humans spread to all corners of the world and reshaped, both intentionally and unintentionally, the environment on a global scale ...
See also The genetics of humanness, The Neanderthal Problem, and Genetic engineering of monkeys using CRISPR.


a last a loved a long the said...


stevesailer said...

If you want to figure out what genes made Neanderthals look like Neanderthals facially, I think it would be cool to check the DNA of the late great William D. Hamilton, who looked like Unfrozen Caveman Darwinist:

Cornelius said...

Interesting video.

I am heterozygous for the diabetes risk gene that he mentions as having introgressed into humans from neanderthal.

ronthehedgehog said...

Then your risk has increased by 1% or less.

Genes have whatever effect they have through the environment for all traits which aren't 100% heritable.

No one is doomed to contracting diabetes type 1 or 2.

Behavioral genetics is so retarded. Blood pressure is exceedingly unreliable yet MZAs correlated on bp nearly as well as on the WAIS, .64 vs .69. Corrected for reliability bp is more heritable than IQ. Yet anyone can have a bp of 100/60 w/o an adrenal tumor or kidney disease.

Cornelius said...

Heterozygous individuals had about 25% greater risk of developing diabetes than people who were homozygous for the homo sapiens sapiens ancestral version. Using a baseline lifetime probability of developing diabetes of 20% - should be higher for this population but we'll take the non-Hispanic white population as our base - the average absolute probability for heterozygous individuals goes up by 5%.

There haven't been any studies on how this gene interacts with other diabetes risk genes so it's hard to say how it increases the probability for any one individual. Without controlling for diet and exercise, my other genes give me a lifetime probability of developing diabetes of about 70%. If the same scaling applies in my case, then my lifetime probability goes up to 87.5%. If I followed anything close to the standard American diet and lifestyle, I think that's probably an accurate number. All four of my grandparents developed diabetes. My father developed diabetes before he was 50. Several of my mother's siblings have diabetes.

For the average person, proper diet and exercise cuts diabetes risk by about 90%. I do eat right and exercise regularly so maybe my risk really is closer to 9%, but that number is still pretty damn high given how healthy my lifestyle is.

ronthehedgehog said...

There is no risk of altitude sickness at the shore of the Dead Sea.
There is no risk of heat stroke at Vostok.
Yet I wouldn't be surprised if some were more likely to come down with these for genetic reasons.
Genes are shadow puppets, and the play they perform depends on the screen or the audience.

They have the highest prevalence of type 2 diabetes
in the world, much more than is observed in other U.S. populations.
While they do not have a greater risk than other tribes, the Pima people
have been the subject of intensive study of diabetes, in part because
they form a homogeneous group.[13]
The general increased diabetes prevalence among Native Americans has
been hypothesized as the result of the interaction of genetic
predisposition (the thrifty phenotype or thrifty genotype as suggested by anthropologist Robert Ferrell in 1984[13])
and a sudden shift in diet from traditional agricultural goods towards
processed foods in the past century. For comparison, genetically similar
O'odham in Mexico have only a slighter higher prevalence of type 2
diabetes than non-O'odham Mexicans[14]

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