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Angela
07-06-18, 20:09
See:

Sara Mathiesen, Iain Mathiesen

"FADS1 and the timing of human adaptation to agriculture"

https://www.biorxiv.org/content/early/2018/06/03/337998

"Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the evidence for this relationship using both modern and ancient DNA data. We document pre-out-of-Africa selection for both the derived and ancestral FADS1 alleles and show that almost all the inhabitants of Europe carried the ancestral allele until the derived allele was introduced approximately 8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under strong selection in these populations. Further, we find that this allele, and other proposed agricultural adaptations including variants at LCT/MCM6, SLC22A4 and NAT2, were not strongly selected until the Bronze Age, 2,000-4,000 years ago. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the development of agriculture although in this case, the putative adaptation precedes the agricultural transition. Our analysis shows that selection at the FADS locus was not tightly linked to the development of agriculture. Further, it suggests that the strongest signals of recent human adaptation may not have been driven by the agricultural transition but by more recent changes in environment or by increased efficiency of selection due to increases in effective population size."

This seems rather counter-intuitive.

Here is Razib Khan's take on it.

See:
https://www.gnxp.com/WordPress/2018/06/03/the-4000-year-explosion/?utm_source=dlvr.it&utm_medium=twitter

"The derived allele, embedded in haplotype D in the above preprint, seems more optimized for plant-based diets, because of the higher activity of synthesis of LCPUFAs (which one might otherwise obtain from marine resources, as is likely among Inuit).So the standard model is that the Neolithic changed things, as humans began to adapt to cereal-based diet diets. This preprint suggests maybe not:"

"The authors are explicit that the derived allele at FADS1, which is at ~60% in modern Europeans, was under strong selection during the Bronze Age. In fact, this allele, which is common in Africans, may have been absent in most Paleolithic Eurasians. Using various methods they infer in fact that the ancestors of non-Africans may have been subject to selection for the ancestral variant. Their timing estimates indicate that this predates the standard expansion period starting ~60,000 BP (there was also an older selection event for the derived variant within Africa). Additionally, the authors posit that the derived variant was introduced into Europeans due to the Basal Eurasian ancestry in farmers."

https://www.gnxp.com/WordPress/wp-content/uploads/2018/06/Screenshot-2018-06-04-00.10.47.png (https://www.biorxiv.org/content/early/2018/06/03/337998?rss=1)
The figure above shows a most interesting result from a new preprint, FADS1 and the timing of human adaptation to agriculture (https://www.biorxiv.org/content/early/2018/06/03/337998?rss=1). It shows the allele frequency change using ancient Eurasian genomes for the derived allele at FADS1.
In case you don’t know why FADS1 is important, it’s been implicated in variation long-chain polyunsaturated (https://en.wikipedia.org/wiki/Polyunsaturated) fatty acids (https://en.wikipedia.org/wiki/Fatty_acids) (LC-PUFA) metabolism. The derived allele, embedded in haplotype D in the above preprint, seems more optimized for plant-based diets, because of the higher activity of synthesis of LCPUFAs (which one might otherwise obtain from marine resources, as is likely among Inuit).
So the standard model is that the Neolithic changed things, as humans began to adapt to cereal-based diet diets. This preprint suggests maybe not:


Our analysis shows that selection at the FADS locus was not tightly linked to the development of agriculture. Further, it suggests that the strongest signals of recent human adaptation may not have been driven by the agricultural transition but by more recent changes in environment or by increased efficiency of selection due to increases in effective population size.


The authors are explicit that the derived allele at FADS1, which is at ~60% in modern Europeans, was under strong selection during the Bronze Age. In fact, this allele, which is common in Africans, may have been absent in most Paleolithic Eurasians. Using various methods they infer in fact that the ancestors of non-Africans may have been subject to selection for the ancestral variant. Their timing estimates indicate that this predates the standard expansion period starting ~60,000 BP (there was also an older selection event for the derived variant within Africa). Additionally, the authors posit that the derived variant was introduced into Europeans due to the Basal Eurasian ancestry in farmers.

(https://www.amazon.com/exec/obidos/ASIN/B071SLPWVL/geneexpressio-20/ref=as_at?creativeASIN=0981519423&linkCode=w61&imprToken=WvNSQCwEIP9qt7KZM0qiUA&slotNum=55)They posit two dynamics that might drive the Bronze Age selection events. First, they suggest that the change in environment was actually more dramatic than that during the Paleolithic-Neolithic transition. Second, they suggest that effective populations were much smaller before the Bronze Age, so selection was not as efficacious (or, more precisely, drift effects were dominant in shaping variation)."

"Second, one of the major takeaways from The Fate of Rome (https://www.amazon.com/exec/obidos/ASIN/B071SLPWVL/geneexpressio-20/ref=as_at/?imprToken=LpkHwvjD9DZhnme4GGPFmQ&slotNum=1&creativeASIN=0981519423&linkCode=w61&imprToken=WvNSQCwEIP9qt7KZM0qiUA&slotNum=55) is that pandemics probably weren’t a feature of Neolithic small-scale societies. Rather, pandemics relied on long-distance trade and movement, as well as concentrations such as urban centers. Though certain endemic diseases probably arose in the Neolithic, the periodic sweep of pandemics required greater social and cultural complexity and overall human density.

The analogy then is rather straightforward. Just as microbes can move faster and more efficiently in an interconnected world, so such a world is much closer to a panmictic one. Earlier work suggested that effective population size of Neolithic farmers was not particularly small, but perhaps there are dynamics being missed by that simple summary value when it comes to the interconnectedness of the Eurasian landscape triggered by the emergence of pastoralism, and the necessary reaction of larger-scale polities.

"A simple test of this would be to compare selection signals in a place like Papua New Guinea, which did not seem to undergo the same sort of pressures (https://www.sanger.ac.uk/news/view/huge-genetic-diversity-among-papuan-new-guinean-peoples-revealed) as Bronze Age Eurasian societies in relation to reduced diversity. I presume that New World societies as well would be an interesting test."

Maciamo
08-06-18, 20:47
It is unexpected that derived alleles of genes associated with a plant-based diet, such as FADS1 (converting plant-based omega-3 to animal-specific omega-3) and AMY1 (amylase production to digest starchy foods) were not selected during Neolithic period, but during the Late Bronze to Iron Age.

It makes sense for other genes like LCT/MCM6 (latcase persistence) as it was useful for pastoralist tribes relying on cow milk.

What event could have caused the stronger selection of FADS1 and AMY1? My first thought is that meat production fell close to zero, forcing people to rely exclusively on plant sources to obtain their omega 3 and having a heavily grain-based diet. Neolithic farmers practised hunting and fishing to complement their diets. Pastoralist Indo-European tribes were mostly cow herders. What if the elite from the Late Bronze Age monopolised meat for themselves, leaving the common people with only grain, thus forcing natural selection among that segment of society?

I am not sure what to make of SLC22A4 and NAT2. The former is an ergothioneine (https://en.wikipedia.org/wiki/Ergothioneine) transporter and ergothioneine is found in liver, kidney, black beans, kidney beans, oat bran, and some mushrooms. Unless people suddenly started eating much more beans and oats from 4000 years ago, that doesn't help us much. NAT2 is an enzyme associated with protection against carcinogens and drug toxicity.

Angela
08-06-18, 23:40
It is unexpected that derived alleles of genes associated with a plant-based diet, such as FADS1 (converting plant-based omega-3 to animal-specific omega-3) and AMY1 (amylase production to digest starchy foods) were not selected during Neolithic period, but during the Late Bronze to Iron Age.

It makes sense for other genes like LCT/MCM6 (latcase persistence) as it was useful for pastoralist tribes relying on cow milk.

What event could have caused the stronger selection of FADS1 and AMY1? My first thought is that meat production fell close to zero, forcing people to rely exclusively on plant sources to obtain their omega 3 and having a heavily grain-based diet. Neolithic farmers practised hunting and fishing to complement their diets. Pastoralist Indo-European tribes were mostly cow herders. What if the elite from the Late Bronze Age monopolised meat for themselves, leaving the common people with only grain, thus forcing natural selection among that segment of society?

I am not sure what to make of SLC22A4 and NAT2. The former is an ergothioneine (https://en.wikipedia.org/wiki/Ergothioneine) transporter and ergothioneine is found in liver, kidney, black beans, kidney beans, oat bran, and some mushrooms. Unless people suddenly started eating much more beans and oats from 4000 years ago, that doesn't help us much. NAT2 is an enzyme associated with protection against carcinogens and drug toxicity.

Yes, the paper's findings seem to go against common sense and what we know of subsistence strategies during these different periods. Perhaps it was something like what you suggest, if they're correct.