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"Reconstruction of nine thousand years of agriculture-based diet and impact on human genetic diversity in Asia"

https://www.biorxiv.org/content/bior...47709.full.pdf

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"Domestication of crops and animals during the Holocene epoch played a critical role in shaping human culture, diet and genetic variation. This domestication process took place across a span of time and space, especially in Asia. We hypothesize that domestication of plants and animals around the world must have influenced the human genome differentially among human populations to a far greater degree than has been appreciated previously. The range of domesticated foods that were available in different regions can be expected to have created regionally distinct nutrient intake profiles and deficiencies. To capture this complexity, we used archaeobotanical evidence to construct two models of dietary nutrient composition over a 9000 year time span in Asia: one based on Larson et al. (2014) and measured through composition of 8 nutrients, and another taking into account a wider range of crops, cooking and lifestyle variation, and the dietary variables glycemic index and carbohydrate content. We hypothesize that the subtle dietary shifts through time and space have also influenced current human genetic variation among Asians. We used statistical methods BayeScEnv, BayeScan and Baypass, to examine the impact of our reconstructed long-term dietary habits on genome-wide genetic variation in 29 current-day Asian populations (Figure S1,
Figure 1, Figure 2). Our results show that genetic variation in diet-related pathways is correlated with dietary differences among Asian populations. SNPs in five genes, GHR, LAMA1, SEMA3A, CAST and TCF7L2, involved in the gene ontologies ‘salivary gland morphogenesis’ and ‘negative regulation of type B pancreatic cell apoptotic process’ suggest that metabolism may have been primary targets of selection driven by dietary shifts. These shifts may have influenced biological pathways in ways that have a lasting impact on health. We present a case that archaeobotanical evidence can provide valuable insight for understanding how historical human niche construction might have influenced modern human genetic variation."

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Southwest Asian populations show higher micro- and macro-nutrient abundancethan East and South AsiansOur primary dietary model (see Methods) infers that the Southwest Asian populations(mostly sampled from present-day Pakistan) had a greater increase in carbohydrates, lipids and protein content due to domestication events from 9000 years ago. In contrast,South Asian populations showed the latest and at least these three major dietary changesin their diets, as domestication started later here. The greatest nutrient increases in allpopulations due to diet changes were carbohydrates, followed by protein, then lipids.Separated into segments of 3000 years, consumption of all three components from thedomesticated diet increased over time, following known increased adoption ofdomestication practices throughout Asia (Figure 2a, Tables S1-8).Similarly, micronutrients zinc, iron, omega-3 and omega-6 fatty acid content from the dietdue to domestication were higher in Southwest Asian populations, followed by East Asiaand South Asia populations. The most dramatic differences were observed for omega-3fatty acids, with Southwest Asia showing higher increases in their diet over the 9000 yearduration compared to the other populations. South Asian populations (excluding theSouthwest Asian populations, mostly located in present-day Pakistan) showed loweramounts of each of these four nutrients compared to the other two populations (Figure2b, Tables S1-8)"

"Modeling intra – and inter-population variability in carbohydrate consumptionIn the second model, farming communities (agricultural and cattle herding) had a highercarbohydrate content in their diet due to domestication, across all ancestry groups.However, East Asian agricultural populations had lower levels of carbohydrate contentcompared to South Asian and Southwest Asian populations. We found substantialgeographic and population-level variability in dietary habits and nutritional outcomes across subsistence groups, as we used fine-scale geographical information to constructpopulation diet (Figure 3). Hunter-gatherers’ diet showed lower levels of carbohydratecontent, but similar levels of glycemic index to agricultural populations, due to higherpresence of fruit in our models. The pastoralist populations showed very similar glycemicindex values and carbohydrate content to other populations with both geographic andgenetic similarity, i.e. ancestry group 2. We saw a similar inverse relationship betweenglycemic index and carbohydrate content, across ancestry groups. For example, ancestrygroups 2 and 4 show higher carbohydrate content, but lower average glycemic index.Stable agriculture and crop husbandry were responsible for those increases incarbohydrate content (Figure 3, Tables S9-S11).The carbohydrate content in the second dietary model will differ from the first becausethe dietary composition in Model 1 referred only to the crops in Larson et al. (2014), andcarbohydrate consumption were tailored to specific populations in Model 2, incorporating pre-agricultural diet as well."

"Little overlap between selection tests, but common gene ontology pathwaysacross tests and nutrientsWe subsequently analyzed the top 1% of variants from the three Bayesian tests (seeSTAR Methods) for variants that have been reported to be associated with dietaryadaptations, and for overlaps in the results for the three Bayesian tests. Analysis of thetop 1% of the variants showed no statistically significant overlap between the three tests(Figure S2). Genes FADS1/FADS2, OCA2, TYR, LRP2, ADH1B and CYP24A1,previously reported to be under diet-mediated selection, appear in one or more of the tophits for several dietary variables in both dietary models (Figure S3)."