RT Journal Article SR Electronic T1 Reconstruction of nine thousand years of agriculture-based diet and impact on human genetic diversity in Asia JF bioRxiv FD Cold Spring Harbor Laboratory SP 747709 DO 10.1101/747709 A1 Srilakshmi M. Raj A1 Allison Pei A1 Matthieu Foll A1 Florencia Schlamp A1 Laurent Excoffier A1 Dorian Q. Fuller A1 Toomas Kivisild A1 Andrew G. Clark YR 2019 UL http://biorxiv.org/content/early/2019/08/28/747709.abstract AB 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.