Deciphering the complex evolution of genes involved in human adaptation to diet – NUTGENEVOL

One of the greatest challenges in human evolutionary genetics is to elucidate the evolution of biological multigenic traits. The nutritional transitions that occurred during human evolution represent major changes in our environment. One of these major transitions is the emergence of agriculture in human societies, for the first time 10,000 yrs ago, when some populations shifted their predominantly meat diet to a predominantly cereal diet. Before this major transition, genes favouring insulin resistance and gluconeogenesis were selected for, in order to constantly maintain sufficient level of glucose in the blood. These genes may now be detrimental in present societies, because under the present high carbohydrate diet, insulin resistance and gluconeogenesis may lead to metabolic disorders such as diabetes, obesity, and hypertension. In order to understand how genes involved in alimentary processes and associated with diabetes have evolved in response to different selective pressures, we will comparatively study different societies that have lived for thousands of years under contrasted diets. This case study will be conducted in Central Asia where pastoral societies and agriculturist societies still co-exist. Pastoralists are thought to have a higher input of meat and diary products compared to agriculturists whose alimentation is mainly based on cereals. Methods We will take phenotypic measurements (nutritional anthropometry, blood measurements of fasting glucose and insulin, high density lipoprotein cholesterol and triglycerides) for three ethnic groups with different food intake. We will perform alimentation surveys and we will sample blood for DNA analyses. This will allow us to study the sequence polymorphism for 10 major genes involved in insulin resistance/sensitivity. We will first apply classical selection tests to these sequences. Then we will develop new multi-locus selection tests that may be more powerful in this context. In parallel, a simulation study will enable us to better understand the evolution of this complex trait under different nutritional conditions and assess the efficiency of the classical and newly developed tests of selection in this context..