title: The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic.
abstract: OBJECTIVE
  The C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution. Here we hypothesize that this new Neolithic diet, which originated in the sunny warm and dry climates of the Middle East, was carried by migrating farmers into the chilly and damp environments of Europe where iron is a critical micronutrient for effective thermoregulation. We argue that the C282Y allele was an adaptation to this novel environment.
  
  
  METHODS
  To address our hypothesis, we compiled C282Y allele frequencies, known Neolithic sites in Europe and climatic data on temperature and rainfall for statistical analysis.
  
  
  RESULTS
  Our findings indicate that the geographic cline for C282Y frequency in Europe increases as average temperatures decrease below 16°C, a critical threshold for thermoregulation, with rainy days intensifying the trend.
  
  
  CONCLUSIONS
  The results indicate that the deleterious C282Y allele, responsible for most cases of hemochromatosis, may have evolved as a selective advantage to culture and climate during the European Neolithic.
authors.affiliation: Department of Earth and Environmental Systems, Indiana State University, Terre Haute, IN, 47809.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Heath
authors.affiliation: Department of Biology, Indiana State University, Terre Haute, IN, 47809.
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Axton
authors.affiliation: Department of Anthropology, University of Utah, Salt Lake City, UT, 84112.
authors.forename: John M
authors.initials: JM
authors.lastname: McCullough
authors.affiliation: Department of Anthropology, University of Utah, Salt Lake City, UT, 84112.
authors.forename: Nathan
authors.initials: N
authors.lastname: Harris
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000885:Anthropology, Physical; D005075:Biological Evolution; D001833:Body Temperature Regulation / Q000235:genetics*; D002980:Climate; D003468:Cultural Evolution / Q000266:history*; D005060:Europe; D005787:Gene Frequency / Q000235:genetics*; D000071020:Hemochromatosis Protein / Q000235:genetics*; D049690:History, Ancient; D006801:Humans; D019266:Iron, Dietary / Q000378:metabolism; D009154:Mutation; D013696:Temperature; D014887:Weather
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D019266:Iron, Dietary
keywords: dietary iron; selection; thermoregulation