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Several studies demonstrated that populations living in the Tibetan plateau are genetically and physiologically adapted to high-altitude conditions, showing genomic signatures ascribable to the action of natural selection. However, so far most of them relied solely on inferences drawn from the analysis of coding variants and point mutations. To fill this gap, we focused on the possible role of polymorphic transposable elements in influencing the adaptation of Tibetan and Sherpa highlanders. To do so, we compared high-altitude and middle/low-lander individuals of East Asian ancestry by performing in silico analyses and differentiation tests on 118 modern and ancient samples. We detected several transposable elements associated with high altitude, which map genes involved in cardiovascular, hematological, chem-dependent and respiratory conditions, suggesting that metabolic and signaling pathways taking part in these functions are disproportionately impacted by the effect of environmental stressors in high-altitude individuals. To our knowledge, our study is the first hinting to a possible role of transposable elements in the adaptation of Tibetan and Sherpa highlanders., Competing Interests: Declaration of competing interest The Authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Epigenetic estimators based on DNA methylation levels have emerged as promising biomarkers of human aging. These estimators exhibit natural variations across human groups, but data about indigenous populations remain underrepresented in research. This study aims to investigate differences in epigenetic estimators between two distinct human populations, both residing in the Gran Chaco region of Argentina, the Native-American Wichí, and admixed Criollos who are descendants of intermarriages between Native Americans and the first European colonizers, using a population genetic approach., Methodology: We analyzed 24 Wichí (mean age: 39.2 ± 12.9 yo) and 24 Criollos (mean age: 41.1 ± 14.0 yo) for DNA methylation levels using the Infinium MethylationEPIC (Illumina) to calculate 16 epigenetic estimators. Additionally, we examined genome-wide genetic variation using the HumanOmniExpress BeadChip (Illumina) to gain insights into the genetic history of these populations., Results: Our results indicate that Native-American Wichí are epigenetically older compared to Criollos according to five epigenetic estimators. Analyses within the Criollos population reveal that global ancestry does not influence the differences observed, while local (chromosomal) ancestry shows positive associations between specific SNPs located in genomic regions over-represented by Native-American ancestry and measures of epigenetic age acceleration (AgeAccelHannum). Furthermore, we demonstrate that differences in population ecologies also contribute to observed epigenetic differences., Conclusions and Implications: Overall, our study suggests that while the genomic history may partially account for the observed epigenetic differences, non-genetic factors, such as lifestyle and ecological factors, play a substantial role in the variability of epigenetic estimators, thereby contributing to variations in human epigenetic aging., Competing Interests: The authors declare no conflict of interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

Since prehistoric times, Italy has represented a bridge between peoples, genes and cultures. Its peculiar geographical position explains why: it is located in the center of the Mediterranean Sea, flanked by the Balkans and the Hellenic Peninsula to the east, Iberia to the west and surrounded by North Africa to the south and central Europe to the north. This makes Italy of extraordinary interest for the study of some different aspects of human diversity. Here we overview current knowledge regarding the relationships between the structure of the genetic variation of Italian populations and the geographical, ecological and cultural factors that have characterized their evolutionary history. Human presence in Italian territory is deeply rooted in the past. Lithic artifacts produced by the genus Homo and remains of Homo sapiens are among the earliest to have been found on the continent, as shown by the lithic industry of Pirro Nord (between 1.3 and 1.6 Mya) and the dental remains of the "Grotta del Cavallo" (between 45 and 43 Kya). Genetic and genomic studies relating to existing and extinct human groups have shed light on the migrations from Europe, Africa and Asia that created the ancient layers of the genetic structure of today's Italian populations, especially before the Iron Age. The important role of isolation (genetic and cultural) in shaping genetic structure is clearly visible in the patterns of intra- and inter-population diversity observed among Italian ethno-linguistic minorities that settled on the peninsula and on the major islands until the 19th century. Finally, selective pressures have likely driven the distribution of originally adaptive variants and haplotypes that now confer protection or susceptibility to major diseases such as diabetes and cardiovascular disease (in northern Italy) and tuberculosis and leprosy (in the south). What emerges is a picture where the combined effects of migration, isolation and natural selection generated by the interplay of geography, environment and culture have shaped a complex pattern of human diversity that is unique in Europe and which goes hand in hand with today's rich animal and plant biodiversity. In a nutshell, scientific evidence and cultural heritage paint Italy as a place with extremely diverse environments where distant peoples have met since the deep past, bringing and sharing genes and ideas.

Heiniger, Grégory, Simon Walbaum, Claudio Sartori, Alban Lovis, Marco Sazzini, Andrew Wellman, and Raphael Heinzer. Altitude-Induced Sleep Apnea Is Highly Dependent on Ethnic Background (Sherpa Vs. Tamang). High Alt Med Biol . 23:165-172, 2022. Rationale: High altitude-induced hypocapnic alkalosis generates central sleep apnea (CSA). In Nepal, two ethnic groups live at medium-to-high altitude: Tamangs originate from low-altitude Tibeto-Burman populations, whereas Sherpas descend from high-altitude Tibetans. Objective: To compare apnea severity at low and high altitude between Sherpas and Tamangs. Methods: Polygraphy recordings, including airflow and oxygen saturation, were performed in Nepal at "low" (2,030 m) and "high" (4,380 m) altitudes. Resting ventilation ( V ̇ E ) and mixed-exhaled CO 2 (F E CO 2 ) were also measured at the same altitudes. Differences in apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and % of nocturnal periodic breathing (NPB) at the two altitudes were compared between ethnicities. Measurements and Main Results: Twenty Sherpas and 20 Tamangs were included (males, median [interquartile range] age: 24.5 [21.5-27.8] years vs. 26.0 [21.5-39.8] years, body mass index: 23.9 [22.1-26.1] kg/m 2 vs. 25.21 [20.6-27.6] kg/m 2 ). Compared with Tamangs, Sherpas showed a lower increase in AHI (+7.5 [2.6-17.2]/h vs. +31.5 [18.2-57.3]/h, p  < 0.001), ODI (+13.8 [5.5-28.2]/h vs. +42.0 [22.6-77.6]/h, p  < 0.001), and NPB proportion (+0.9 [0-3.5]% vs. +12.8 [3.1-27.4]%, p  < 0.001) from low to high altitude. Resting V ̇ E was higher in Sherpas versus Tamangs at both low (8.45 [6.89-10.70] l/min vs. 6.3 [4.9-8.3] l/min, p  = 0.005) and high (9.7 [8.5-11] l/min vs. 8.74 [7.39-9.73] l/min, p  = 0.020) altitudes, whereas the mean ± standard deviation F E CO 2 decrease between low and high altitude was greater in Tamangs versus Sherpas (-0.50% ± 0.44% vs. -0.80% ± 0.33%, p  < 0.023). Conclusion: Overall, altitude-adapted Sherpas showed a 3.2-times smaller increase in sleep-disordered breathing between low and high altitude compared with Tamangs, and higher ventilation and a smaller drop in F E CO 2 at high altitude. These data suggest that genetic differences in breathing control can be protective against CSA.

Native American genetic ancestry has been remarkably implicated with increased risk of diverse health issues in several Mexican populations, especially in relation to the dramatic changes in environmental, dietary, and cultural settings they have recently undergone. In particular, the effects of these ecological transitions and Westernization of lifestyles have been investigated so far predominantly on Mestizo individuals. Nevertheless, indigenous groups, rather than admixed Mexicans, have plausibly retained the highest proportions of genetic components shaped by natural selection in response to the ancient milieu experienced by Mexican ancestors during their pre-Columbian evolutionary history. These formerly adaptive variants have the potential to represent the genetic determinants of some biological traits that are peculiar to Mexican people, as well as a reservoir of loci with possible biomedical relevance. To test such a hypothesis, we used genome-wide genotype data to infer the unique adaptive evolution of Native Mexican groups selected as reasonable descendants of the main pre-Columbian Mexican civilizations. A combination of haplotype-based and gene-network analyses enabled us to detect genomic signatures ascribable to polygenic adaptive traits plausibly evolved by the main genetic clusters of Mexican indigenous populations to cope with local environmental and/or cultural conditions. Some of these adaptations were found to play a role in modulating the susceptibility/resistance of these groups to certain pathological conditions, thus providing new evidence that diverse selective pressures have contributed to shape the current biological and disease-risk patterns of present-day Native and Mestizo Mexican populations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)