title: Epigenetic Variability across Human Populations: A Focus on DNA Methylation Profiles of the KRTCAP3, MAD1L1 and BRSK2 Genes.
abstract: Natural epigenetic diversity has been suggested as a key mechanism in microevolutionary processes due to its capability to create phenotypic variability within individuals and populations. It constitutes an important reservoir of variation potentially useful for rapid adaptation in response to environmental stimuli. The analysis of population epigenetic structure represents a possible tool to study human adaptation and to identify external factors that are able to naturally shape human DNA methylation variability. The aim of this study is to investigate the dynamics that create epigenetic diversity between and within different human groups. To this end, we first used publicly available epigenome-wide data to explore population-specific DNA methylation changes that occur at macro-geographic scales. Results from this analysis suggest that nutrients, UVA exposure and pathogens load might represent the main environmental factors able to shape DNA methylation profiles. Then, we evaluated DNA methylation of candidate genes (KRTCAP3, MAD1L1, and BRSK2), emerged from the previous analysis, in individuals belonging to different populations from Morocco, Nigeria, Philippines, China, and Italy, but living in the same Italian city. DNA methylation of the BRSK2 gene is significantly different between Moroccans and Nigerians (pairwise t-test: CpG 6 P-value = 5.2*10 (-) (3); CpG 9 P-value = 2.6*10 (-) (3); CpG 10 P-value = 3.1*10 (-) (3); CpG 11 P-value = 2.8*10 (-) (3)). Comprehensively, these results suggest that DNA methylation diversity is a source of variability in human groups at macro and microgeographical scales and that population demographic and adaptive histories, as well as the individual ancestry, actually influence DNA methylation profiles.
authors: Department of Biological Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Italy cristina.giuliani2@unibo.it.
authors: Cristina
authors: C
authors: Giuliani
authors: Department of Biological Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Italy.
authors: Marco
authors: M
authors: Sazzini
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy Interdepartmental Center "L. Galvani" (C.I.G.), University of Bologna, Italy.
authors: Maria Giulia
authors: MG
authors: Bacalini
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy Interdepartmental Center "L. Galvani" (C.I.G.), University of Bologna, Italy.
authors: Chiara
authors: C
authors: Pirazzini
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy Interdepartmental Center "L. Galvani" (C.I.G.), University of Bologna, Italy.
authors: Elena
authors: E
authors: Marasco
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy.
authors: Elisa
authors: E
authors: Fontanesi
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy Interdepartmental Center "L. Galvani" (C.I.G.), University of Bologna, Italy IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors: Claudio
authors: C
authors: Franceschi
authors: Department of Biological Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Italy.
authors: Donata
authors: D
authors: Luiselli
authors: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy Interdepartmental Center "L. Galvani" (C.I.G.), University of Bologna, Italy Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors: Paolo
authors: P
authors: Garagnani
mesh_terms: D000222:Adaptation, Physiological; D018797:Cell Cycle Proteins / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D014644:Genetic Variation; D006801:Humans; D007633:Keratins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins; D007633:Keratins; C507732:Brsk2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: DNA methylation variability; environmental interaction; human adaptation; population epigenetics