Giampaolo MorcianoJC - 04/06/2010

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.

61 human populations: 52 in the HGDP 4 HapMap Phase III

5 additional populationsAFRICA 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

Luhya, Maasai, Tuscans, Gujarati

Vasekela Kung, Amhara, Naukan Yup’ik and Maritime Chukchee,

Australian Aborigines

Bailey’s Ecoregion Map

For each population were gathered…

…according to their main mode of subsistence and dietary

specialization.

Detecting signals between SNPs andenvironmental 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

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.

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

(A) Roots and tubers : Yoruba, Papuan, Melanesian, Karitiana, Surui (B) Foraging : Biaka, Vasekela, Mbuti, Maritime Chukchee, Australian Aborigines

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

Two NS SNPs have extremely high BFs and provide convincing signals of adaptations to dietary specializations:

Rs162036 (MTRR gene): folate – poor roots and tuberspathways 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

Identification of Pathways that were targeted by selection

Results of genome – wide association studieswith disease and other complex traits

DiscussionSelection 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!

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

The strongest signal was observed for the polar domain

- cold temperature- low UV radiation - limited resources

energy metabolism and temperature homeostasis

a lesser signal extent for dry and humid temperate domains

may reflect ancient adaptations during the dispersal of modern human populations

lack of a significant excess of signals associated withthe humid tropical domain

may be due to a combination of factors

This approach is similar to previous analyses based on FST:

1.compare populations on the basis of environmental variables2.use of a test statistic (BF)

The overlap in the tails from global FST and the minimum ranks for subsistence and ecoregion, respectively, are slightly less than expected by chance.

Maybe results due solely to background selection. The elimination of deleterious alleles reduces the effective population size of the genic regions compared to the less constrained nongenic regions.

Purifying rather than positive selection could potentially account for the excess of genic SNPs correlated with environmental variables. They cannot rule out this possibility, but…

- the enrichment of genic and NS SNPs becomes more pronounced in the more extreme lower tails- the enrichment of NS SNPs is quantitatively greater than genic SNPs