Nutrigenomics in the context of evolution

Abstract

Nutrigenomics describes the interaction between nutrients and our genome. Since the origin of our species most of these nutrient-gene communication pathways have not changed. However, our genome experienced over the past 50,000 years a number of evolutionary pressures, which are based on the migration to new environments concerning geography and climate, the transition from hunter-gatherers to farmers including the zoonotic transfer of many pathogenic microbes and the rather recent change of societies to a preferentially sedentary lifestyle and the dominance of Western diet. Human populations responded to these challenges not only by specific anthropometric adaptations, such as skin color and body stature, but also through diversity in dietary intake and different resistance to complex diseases like the metabolic syndrome, cancer and immune disorders. The genetic basis of this adaptation process has been investigated by whole genome genotyping and sequencing including that of DNA extracted from ancient bones. In addition to genomic changes, also the programming of epigenomes in pre- and postnatal phases of life has an important contribution to the response to environmental changes. Thus, insight into the variation of our (epi)genome in the context of our individual's risk for developing complex diseases, helps to understand the evolutionary basis how and why we become ill. This review will discuss the relation of diet, modern environment and our (epi)genome including aspects of redox biology. This has numerous implications for the interpretation of the risks for disease and their prevention.

Keywords: Disease risk; Evolution; Human genome; Immunity; Lactase persistence; Nutrigenomics.

Fig. 1

Risk allele frequency of genetic variants. ORs indicate the strength of a genetic effect. Main emphasis on the identification of associations within the diagonal box. Whole genome sequencing of large numbers of individuals identifies far more low frequency SNVs with intermediate ORs (center).

Fig. 2

Homo sapiens migrations. Anatomically modern humans developed in East Africa and spread first over the whole continent before they started some 75,000 years ago to migrate to Asia. From there they settled in Oceania, Europe and the Americas.

Fig. 3

Molecular basis of lactase persistence. The genomic region of the genes LCT and MCM6 is shown (A). SNPs located approximately 14 and 22 kb upstream of the TSS of the LCT gene, which are located within introns 13 and 9 of the MCM6 gene, respectively, are associated with lactase persistence. The function of regulatory SNPs is schematically depicted (B). The SNP is part of a transcription factor binding site and provides in one allele (top) high affinity and in the other allele (bottom) low affinity for the transcription factors. In case of rs4988235 at position −13,910 relative to the LCT gene this is POU2F1 (POU class 2 homeobox 1). Moreover, epigenetic effects, such as histone acetylation and methylation as well as DNA methylation can affect the expression of the LCT gene and mediate lactase persistence.