title: Exploring the relationship between lifestyles, diets and genetic adaptations in humans.
abstract: BACKGROUND
  One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. This change might have worked as a selective pressure over the metabolic pathways involved in the breakdown of substances extracted from food. Here we applied a candidate gene approach to investigate whether in populations with different modes of subsistence, diet-related genetic adaptations could be identified in the genes AGXT, PLRP2, MTRR, NAT2 and CYP3A5.
  
  
  RESULTS
  At CYP3A5, strong signatures of positive selection were detected, though not connected to any dietary variable, but instead to an environmental factor associated with the Tropic of Cancer. Suggestive signals of adaptions that could indeed be connected with differences in dietary habits of populations were only found for PLRP2 and NAT2. Contrarily, the demographic history of human populations seemed enough to explain patterns of diversity at AGXT and MTRR, once both conformed the evolutionary expectations under selective neutrality.
  
  
  CONCLUSIONS
  Accumulated evidence indicates that CYP3A5 has been under adaptive evolution during the history of human populations. PLRP2 and NAT2 also appear to have been modelled by some selective constrains, although clear support for that did not resist to a genome wide perspective. It is still necessary to clarify which were the biological mechanisms and the environmental factors involved as well as their interactions, to understand the nature and strength of the selective pressures that contributed to shape current patterns of genetic diversity at those loci.
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. csantos@ipatimup.pt.|Faculty of Sciences, University of Porto, Porto, Portugal. csantos@ipatimup.pt.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valente
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. lfernandez@ipatimup.pt.
authors.forename: Luis
authors.initials: L
authors.lastname: Alvarez
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. sarah.marks@live.co.uk.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Marks
authors.affiliation: Departamento de Toxicología y Legislación Sanitaria, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. amlopezparra@med.ucm.es.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lopez-Parra
authors.affiliation: Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria. walther.parson@i-med.ac.at.|Penn State Eberly College of Science, University Park, Pennsylvania, USA. walther.parson@i-med.ac.at.
authors.forename: Walther
authors.initials: W
authors.lastname: Parson
authors.affiliation: School of Medicine, University of Namibia, Windhoek, Namibia. dr-ockie@iway.na.
authors.forename: Ockie
authors.initials: O
authors.lastname: Oosthuizen
authors.affiliation: School of Medicine, University of Namibia, Windhoek, Namibia. ericao@iway.na.
authors.forename: Erica
authors.initials: E
authors.lastname: Oosthuizen
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. aamorim@ipatimup.pt.|Faculty of Sciences, University of Porto, Porto, Portugal. aamorim@ipatimup.pt.
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. cristian.capelli@zoo.ox.ac.uk.
authors.forename: Cristian
authors.initials: C
authors.lastname: Capelli
authors.affiliation: Departamento de Toxicología y Legislación Sanitaria, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. earroyop@med.ucm.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arroyo-Pardo
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. lgusmao@ipatimup.pt.|DNA Diagnostic Laboratory (LDD), State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil. lgusmao@ipatimup.pt.
authors.forename: Leonor
authors.initials: L
authors.lastname: Gusmão
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. mprata@ipatimup.pt.|Faculty of Sciences, University of Porto, Porto, Portugal. mprata@ipatimup.pt.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Prata
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000483:Alleles; D005075:Biological Evolution; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004032:Diet; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008019:Life Style; D015810:Linkage Disequilibrium; D008049:Lipase / Q000235:genetics; D040641:Quantitative Trait Loci; D012641:Selection, Genetic; D000637:Transaminases / Q000235:genetics
chemical_list: D051544:Cytochrome P-450 CYP3A; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase; D008049:Lipase; C075988:pancreatic lipase related protein 2