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

par Heyer Évelyne - publié le , mis à jour le

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. This transition also lead to the increase of Lactase persistency phenotype, a new phenotype that enables adult individuals to digest fresh milk.

One of the greatest challenges in human evolutionary genetics is to elucidate the evolution of biological multigenic traits.


In order to understand how genes involved in alimentary processes including those associated with diabetes have evolved in response to different selective pressures, we have comparatively studied different societies that have lived for thousands of years under contrasted diets. This case study has been conducted in Central Asia where pastoral societies and agriculturist societies still co-exist. Pastoralists are though to have a higher input of meat and diary products compared to agriculturists whose alimentation is mainly based on cereals.

Adaptation to diet through genes known to be involved in diabetis type II

We took phenotypic measurements (nutritional anthropometry, blood measurements of fasting glucose and insulin, high density lipoprotein cholesterol and triglycerides) for two ethnic groups with different food intake. We performed alimentation surveys and we sampled blood for DNA analyses. This allow us to study the sequence polymorphism for 10 major genes involved in insulin resistance/sensitivity. We have applied classical selection tests to these sequences. The ‘thrifty genotype’ hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants.

Results of this study have been published in European Journal of Human Genetics : Segurel et al, 2013

Protocole :
- Phenotypic measures
- Blood sampling
- Diet questionnaires

comments : see Chicago University

Lactase persistency

Worldwide it has been shown that pastoralist populations show an elevated frequency of lactase persistency phenotype. This is the classical example of bio-cultural evolution. The aim of our study was to document the evolution of the lactase persistence trait in Central Asia, a geographical area that is thought to have been a region of long-term pastoralism. It was recently demonstrated that horse milking practice existed in the Botai culture of Kazakhstan as early as 5,500 BP (Outram et al. 2009). However, the frequency of the lactase persistence trait and its genetic basis in Central Asian populations remain largely unknown. We did here the first genotype-phenotype study of lactase persistence in Central Asia based on 183 individuals, as well as the estimation of the time of expansion of the lactasepersistence associated polymorphism. Our results show a remarkable geneticphenotypic correlation, with the causal polymorphism being the same than in Europe (-13.910C T, rs4988235). The lactase persistence trait is at low frequency in these populations : between 25% and 32% in the Kazakh population (traditionally herders), according to phenotype used, and between 11% and 30% in the Tajiko-Uzbek population (agriculturalists). The difference in lactase persistence between populations, even if small, is significant when using individuals concordant for both excretion of breath hydrogen and the lactose tolerance blood glucose test phenotypes (P 0.018, 25% for Kazakh vs. 11% for Tajiko-Uzbeks), and the difference in frequency of the 13.910*T allele is almost significant (P 0.06, 30% for Kazakhs vs. 19% for Tajiko-Uzbeks). Using the surrounding haplotype, we estimate a date of expansion of the T allele around 6,000–12,000 yrs ago, which is consistent with archaeological records for the emergence of agropastoralism and pastoralism in Central Asia.

Results of this study have been published in Human Biology : Heyer et al, 2011 pdf

Protocole :
- Initial Phenotypic measures
- Second phenotypic measures

Is AGXT a good candidate gene for adaptation to diet rich in meat ?

The Pro11Leu substitution in the AGXT gene, which causes primary hyperoxaluria type 1, is found with high frequency in some human populations (e.g., 5–20% in Caucasians). It has been suggested that this detrimental mutation could have been positively selected in populations with a meat-rich diet. In order to test this hypothesis, we investigated the occurrence of Pro11Leu in both herder and agriculturalist populations from Central Asia. We found a lower frequency of this detrimental mutation in herders, whose diet is more meat-rich, as compared to agriculturalists, which therefore challenges the universality of the previous claim. Furthermore, when combining our original data with previously published results, we could show that the worldwide genetic differentiation measured at the Pro11Leu polymorphism does not depart from neutrality. Hence, the distribution of the variation observed in the AGXT gene could be due to demographic history, rather than local adaptation to diet.

Results of this study have been published in Annals of Human Genetics : Segurel et al, 2009 pdf