Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans

Abstract

Background The cline of human genetic diversity observable across Europe is recapitulated at a micro-geographic scale by variation within the Italian population. Besides resulting from extensive gene flow, this might be ascribable also to local adaptations to diverse ecological contexts evolved by people who anciently spread along the Italian Peninsula. Dissecting the evolutionary history of the ancestors of present-day Italians may thus improve the understanding of demographic and biological processes that contributed to shape the gene pool of European populations. However, previous SNP array-based studies failed to investigate the full spectrum of Italian variation, generally neglecting low-frequency genetic variants and examining a limited set of small effect size alleles, which may represent important determinants of population structure and complex adaptive traits. To overcome these issues, we analyzed 38 high-coverage whole-genome sequences representative of population clusters at the opposite ends of the cline of Italian variation, along with a large panel of modern and ancient Euro-Mediterranean genomes. Results We provided evidence for the early divergence of Italian groups dating back to the Late Glacial and for Neolithic and distinct Bronze Age migrations having further differentiated their gene pools. We inferred adaptive evolution at insulin-related loci in people from Italian regions with a temperate climate, while possible adaptations to pathogens and ultraviolet radiation were observed in Mediterranean Italians. Some of these adaptive events may also have secondarily modulated population disease or longevity predisposition. Conclusions We disentangled the contribution of multiple migratory and adaptive events in shaping the heterogeneous Italian genomic background, which exemplify population dynamics and gene-environment interactions that played significant roles also in the formation of the Continental and Southern European genomic landscapes.

The mitogenome portrait of Umbria in Central Italy as depicted by contemporary inhabitants and pre-Roman remains

“…This microgeographic and diachronic mtDNA portrait of Umbria fits well with recent genetic data on the entire peninsula. The Y-chromosome counterpart pointed to different male ancestries for the Italian populations 24 and the autosomal data revealed several ancient signatures and the largest degree of population structure detected so far in Europe 19,29 . Notably, two of the three published genomic clusters (Sardinia, Northern and Southern Italy) overlap in Central Italy and precisely in Umbria, the "Heart of Italy".…”

“…Concerning the phylogeography of Italy, it is difficult to identify a clear genetic pattern able to discriminate southern, northern and central populations in spite of several attempts based on autosomal and uniparental markers [19][20][21][22][23][24] . Southern populations were mostly influenced by Greek and Arab colonizations, Northern Italians might reflect admixture with French and German-speaking populations, while Central Italy occupies its own intermediate position creating a continuous cline of variation across the peninsula (with Sardinians as outliers) 13,19,[25][26][27][28][29] . Most of these studies were performed on a large geographic scale producing low-definition results and mainly focusing on modern populations.…”

Investigating Mitonuclear Genetic Interactions Through Machine Learning: A Case Study on Cold Adaptation Genes in Human Populations From Different European Climate Regions

“…It is widely described that climate exerted a major role in shaping populations’ genomic diversity by impacting on several human traits, such as body size, skin pigmentation, energy expenditure, and nutrient metabolism ( Hancock et al, 2011 ; Sturm and Duffy, 2012 ; Raj et al, 2013 ; Fumagalli et al, 2015 ; Quagliarello et al, 2017 ; Sazzini et al, 2020 ). At the same time, the mitochondria are crucial for heat production in many organisms and its metabolic role in ATP-production (as well as for a variety of other cellular functions, such as survival/cell death, differentiation, redox and inflammation regulation, and numerous metabolic processes).…”

Dietary, Cultural and Pathogens-related Selective Pressures Shaped Differential Adaptive Evolution Among Native Mexican Populations

“…Unfortunately, this has limited also the identification of the genetic determinants of important biological features of present-day Native and Mestizo Mexican people. In particular, variation underlying adaptive traits that have been shaped by natural selection in relation to the ancestral milieu of these human groups might represent an important reservoir of alleles/haplotypes with potential biomedical relevance (Sazzini et al 2016;Ávila-Arcos et al 2020;Sazzini et al 2020;Landini et al 2020). In fact, the rapid and substantial modifications occurred in modern Mexican societies might have turned some of these biological adaptations into unfavorable (i.e.…”

“…dis-adaptive) traits, thus contributing to differential disease susceptibility among populations with varying proportions of NA ancestry.To test such a hypothesis, we used high-resolution genomic data to infer the adaptive evolution of 15 Native Mexican groups selected as reasonable descendants of the main pre-Columbian Mexican civilizations. For this purpose, we imputed genome-wide data from the Native Mexican Diversity Panel (NMDP) (Moreno-Estrada et al 2014) and we applied a combination of haplotype-based and gene-network analyses to detect genomic signatures ascribable to the occurrence of selective events under a realistic approximation of a polygenic adaptation model (Gnecchi-Ruscone et al 2018;Sazzini et al 2020). Accordingly, we identified different adaptive traits peculiar to the main genetic clusters of Native Mexican populations, thus providing new evidence for diverse selective pressures having contributed to shape their current biological and disease-risk patterns.…”