A string of biological and cultural changes strongly related to the occupation of new environmental contexts has characterized the evolution of the human lineage, especially during the widespread colonization of non-African continents by anatomically modern humans. Therefore, geographically and temporally defined variation of selective pressures acting on the genomes of both H. sapiens ancestors and modern populations triggered genetic adaptations in response to local environments. In particular, necessity to cope with unprecedented nutritional landscapes prompted a number of biological shifts in many human groups, mainly related to the introduction of considerable modifications of their diets and of new challenges to their metabolism [1,2], contributing to influence a variety of traits, among which differential disease susceptibility of human populations due to possible maladaptive processes [3]. In fact, the rate of dietary changes dramatically increased in the very recent evolutionary history of our species, as a consequence of introduction of agricultural and pastoralist practices, of consumption of industrial refined foods and of ever-increasing globalization [4], thus potentially converting some adaptive traits into maladaptive ones. In accordance to this view, increasing discordance between our anciently determined biology and contemporary nutritional or cultural patterns is supposed to have contributed to the spread of several complex diseases, which may represent by-products of past adaptive events due to loci that have become detrimental in modern societies [5]. To test this hypothesis, we have investigated the genetic legacy of natural selection on a panel of about one hundred genes representative of the main players driving functional pathways associated to food digestion and energy balance, or which turned out to be altered in metabolic and nutrition-related diseases. Sequence data for human populations living in different biomes were collected from public databases and used, in combination with unpublished data on individuals affected by certain nutrition-related diseases, to explore patterns of variation at more than 100,000 single nucleotide variants and/or indels. Population differentiation analyses based on the calculation of pairwise Fst indices among genetically homogeneous clusters of populations and on their comparison with genome-wide Fst distributions pointed out a few genes unusually differentiated with respect to average genomic patterns. Haplotype structure and potential deviations from a neutral model of evolution were then investigated at these candidate regions by applying several neutrality tests and by performing calibrated coalescent simulations, to disentangle the interplay between natural selection, demographic events and local mutation/recombination rates in shaping the observed patterns of variation. This enabled to elucidate implications of loci responsible for past adaptive events in the examined diseases, contributing to explain their underlying mechanisms and present-day epidemiological patterns, as well as some of the evolutionary processes that made our genome prone to the side effects of modern environmental stimuli.

Investigating the link between past adaptations and modern diseases: a nutrition-related perspective / Sazzini M.; Quagliariello A.; Cherubini A.; De Fanti S.; Spisni E.; Luiselli D.. - STAMPA. - (2014). (Intervento presentato al convegno European Society for the study of Human Evolution 3 (ESHE 2014) tenutosi a Firenze nel 18-20/9/2014).

Investigating the link between past adaptations and modern diseases: a nutrition-related perspective

SAZZINI, MARCO;QUAGLIARIELLO, ANDREA;CHERUBINI, ANNA;DE FANTI, SARA;SPISNI, ENZO;LUISELLI, DONATA
2014

Abstract

A string of biological and cultural changes strongly related to the occupation of new environmental contexts has characterized the evolution of the human lineage, especially during the widespread colonization of non-African continents by anatomically modern humans. Therefore, geographically and temporally defined variation of selective pressures acting on the genomes of both H. sapiens ancestors and modern populations triggered genetic adaptations in response to local environments. In particular, necessity to cope with unprecedented nutritional landscapes prompted a number of biological shifts in many human groups, mainly related to the introduction of considerable modifications of their diets and of new challenges to their metabolism [1,2], contributing to influence a variety of traits, among which differential disease susceptibility of human populations due to possible maladaptive processes [3]. In fact, the rate of dietary changes dramatically increased in the very recent evolutionary history of our species, as a consequence of introduction of agricultural and pastoralist practices, of consumption of industrial refined foods and of ever-increasing globalization [4], thus potentially converting some adaptive traits into maladaptive ones. In accordance to this view, increasing discordance between our anciently determined biology and contemporary nutritional or cultural patterns is supposed to have contributed to the spread of several complex diseases, which may represent by-products of past adaptive events due to loci that have become detrimental in modern societies [5]. To test this hypothesis, we have investigated the genetic legacy of natural selection on a panel of about one hundred genes representative of the main players driving functional pathways associated to food digestion and energy balance, or which turned out to be altered in metabolic and nutrition-related diseases. Sequence data for human populations living in different biomes were collected from public databases and used, in combination with unpublished data on individuals affected by certain nutrition-related diseases, to explore patterns of variation at more than 100,000 single nucleotide variants and/or indels. Population differentiation analyses based on the calculation of pairwise Fst indices among genetically homogeneous clusters of populations and on their comparison with genome-wide Fst distributions pointed out a few genes unusually differentiated with respect to average genomic patterns. Haplotype structure and potential deviations from a neutral model of evolution were then investigated at these candidate regions by applying several neutrality tests and by performing calibrated coalescent simulations, to disentangle the interplay between natural selection, demographic events and local mutation/recombination rates in shaping the observed patterns of variation. This enabled to elucidate implications of loci responsible for past adaptive events in the examined diseases, contributing to explain their underlying mechanisms and present-day epidemiological patterns, as well as some of the evolutionary processes that made our genome prone to the side effects of modern environmental stimuli.
2014
Proceedings of the European Society for the study of Human Evolution 3
Investigating the link between past adaptations and modern diseases: a nutrition-related perspective / Sazzini M.; Quagliariello A.; Cherubini A.; De Fanti S.; Spisni E.; Luiselli D.. - STAMPA. - (2014). (Intervento presentato al convegno European Society for the study of Human Evolution 3 (ESHE 2014) tenutosi a Firenze nel 18-20/9/2014).
Sazzini M.; Quagliariello A.; Cherubini A.; De Fanti S.; Spisni E.; Luiselli D.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/396739
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