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1. Giampaolo Morciano JC - 04/06/2010

2. Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of ecoregions and dietary components. These aspects of human environments have changed dramatically during human evolution, giving rise to new selective pressures. This study aims to clarify the genetics underlying the adaptative responses to these transitions.

3. 61 human populations: 52 in the HGDP 4 HapMap Phase III 5 additional populations Luhya, Maasai, Tuscans, Gujarati Vasekela Kung, Amhara, Naukan Yup’ik and Maritime Chukchee, Australian Aborigines AFRICA ASIA EUROPA Bantu Ctrl/South Eastern ASIA Adygei Biaka Balochi Khmer Mongola Basque Mandenka Brahui Dai Naxi French Mbuti pygmy Burusho Daur Oroqen North Italian Mozabite Hazara Han (N. China ) She Orcadian San Kalash Han (S. China ) Tu Russian Yoruba Makrani Hezhen Tujia Sardinian Pashtun Japanese Xibo Tuscan Sindhi Lahu Yakut NATIVE AMERICA Uyghur Miao Yi Colombian OCEANIA Karitiana Western ASIA Melanesian Maya Bedouin Papuan Pima Druze Surui

4. Bailey’s Ecoregion Map For each population were gathered… … according to their main mode of subsistence and dietary specialization.

5. Detecting signals between SNPs and environmental variables To assess evidence for selection related to each environmental variable, we contrasted the allele frequencies for each SNP across populations that differ with respect to the environmental variable. Bayesian linear model method BF

6. On the basis of these BFs  a transformed rank statistic that was scaled to be between 0 and 1. Calculating this transformed rank statistic allowed us to control for some aspects of SNP ascertainment and differences in allele frequencies across SNPs. To summarize the evidence for selection for each SNP for the two categories of variables as a whole, we calculated a minimum rank statistic by finding the minimum of the transformed rank statistics across all subsistence and ecoregion variables.

7. Assessing the evidence for an excess of functional SNPs in the tail of the distribution

10. (C) Polar : Russian, Maritime Chukchee, Yakut (D) Dry : Amhara, San, Hazara, Mongola, Xibo, Pima

11. Two NS SNPs have extremely high BFs and provide convincing signals of adaptations to dietary specializations: Rs162036 (MTRR gene): folate – poor roots and tubers pathways  starch and sucrose metabolism and folate biosynthesis Rs4751995 (PLRP2): use of cereals as the main dietary component pathways  role in a plant – based diet Cytogenetic Location: 5p15.3-p15.2

12. Identification of Pathways that were targeted by selection

13. Results of genome – wide association studies with disease and other complex traits

14. Discussion Selection on standing, rather than new alleles, may have played a prominent role in adaptation to new environments, supported by expectations of selection models for quantitative traits, specifically that selection will generate small allele frequency shifts at many loci until the population reaches a new optimum. [No HARD SWEEP MODEL] Some of most interesting signals seem to be adaptations to dietary specializations  cultural adaptations played an important role in our ability to diversify. Genetic adaptations to dietary specializations in human population may be widespread!

15. Hunting and gathering are the modes of subsistence that characterized human populations since their emergence in Africa until the transition to intensive agriculture. Given that our ancestors were foragers, the signal we observe in the contrast between forager and nonforager populations is likely to reflect adaptations to more specialized diets in horticulture, animal farming, and agriculture. NAT2 drug metabolizing enzyme gene