Complex interplay between neutral and adaptive evolution shaped differential genomic background and disease susceptibility along the Italian peninsula

Abstract

The Italian peninsula has long represented a natural hub for human migrations across the Mediterranean area, being involved in several prehistoric and historical population movements. Coupled with a patchy environmental landscape entailing different ecological/cultural selective pressures, this might have produced peculiar patterns of population structure and local adaptations responsible for heterogeneous genomic background of present-day Italians. To disentangle this complex scenario, genome-wide data from 780 Italian individuals were generated and set into the context of European/Mediterranean genomic diversity by comparison with genotypes from 50 populations. To maximize possibility of pinpointing functional genomic regions that have played adaptive roles during Italian natural history, our survey included also ~250,000 exomic markers and ~20,000 coding/regulatory variants with well-established clinical relevance. This enabled fine-grained dissection of Italian population structure through the identification of clusters of genetically homogeneous provinces and of genomic regions underlying their local adaptations. Description of such patterns disclosed crucial implications for understanding differential susceptibility to some inflammatory/autoimmune disorders, coronary artery disease and type 2 diabetes of diverse Italian subpopulations, suggesting the evolutionary causes that made some of them particularly exposed to the metabolic and immune challenges imposed by dietary and lifestyle shifts that involved western societies in the last centuries.

A bird’s-eye view of Italian genomic variation through whole-genome sequencing

“…Nonetheless, caution and further studies will be needed to assess the role of the suggestive signals. Recently published results based on array data pinpointed the genetic diversity in the Italian peninsula [6] along with the presence of isolates [8]. These insights showed the lack of homogeneity of genomes coming from different regions of Italy in terms of diverse genomic aspects (population structure, natural selection signatures, deleterious variants distribution and HKO) and, as a consequence, how the usage of only one reference population for Italians, such as the Tuscans (TSI), is not reliable.…”

“…only a small group of subjects from Italy -Tuscany -and Spain). In particular, the Italian peninsula, characterised by past and recent migration events [6,7] and also widespread isolation [8][9][10] is a fascinating region to describe and understand. We characterised whole-genome sequences from isolated populations localised in three different geographical areas of Italy: North-West (Val Borbera -VBI), North-East (Friuli Venezia Giulia -FVG) and South-East (Carlantino -CAR); for which the presence of stratification [8,11] and the different levels of isolation were demonstrated [12].…”

A Regionalized Genome-Based Mexican Diet Improves Anthropometric and Metabolic Parameters in Subjects at Risk for Obesity-Related Chronic Diseases

“…The physiopathological mechanisms underlying the metabolic diseases common in modern populations may rely on their particular evolutionary history that currently influences their patterns of disease risk [2]. Accordingly, populations presenting diet-related adaptive gene (DRAG) polymorphisms selected by their ancestral dietary contexts and currently exposed to the well-described Western dietary pattern and lifestyle are at increased risk of abnormal metabolic conditions and obesity-related CD [3][4][5]. Not more than 500 years ago the Mexican Native American (NA) populations, who relied on a pre-Hispanic diet since the emergence of plant domestication and agriculture (at least 5 kya), were subjected to a genetic and food-culture admixture with the arrival of Spaniards and the introduction of new ingredients from the Old World [6].…”

Ancient and recent admixture layers in Sicily and Southern Italy trace multiple migration routes along the Mediterranean

“…On the other hand, while aDNA data from Southern Italy and Sicily are still limited, genome-wide analyses of modern populations from these areas mainly consisted to wide-range surveys without specific fine-scale insights 18, 35, 36 .…”