The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

Abstract

ObjectivesThe 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.Materials and MethodsTo address our hypothesis, we compiled C282Y allele frequencies, known Neolithic sites in Europe and climatic data on temperature and rainfall for statistical analysis.ResultsOur 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.DiscussionThe 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. Am J Phys Anthropol 160:86–101, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

Letter to the editor: Reply to Kasvosve (2016)

“…Kasvosve (in press) discusses the Fpn Q248H allele mutation for iron retention in African populations and argues that a mechanism accounting for the variation in frequency has not been identified. He concurs with Delanghe, Speeckaert, and De Buyzere (in press) that it is unlikely due to chilly and damp climates proposed to account for the frequency variability of the C282Y allele for iron retention found in European populations (Heath, Axton, McCullough, & Harris, 2016).…”

“…Other mutations that increase iron stores, such as the Q248H allele, rarely result in hemochromatosis (Aguilar-Martinez et al, 2011;Feder et al, 1996;Hanson, Imperatore, & Burke, 2001). Therefore we (Heath, Axton, McCullough & Harris, 2016) focused on accounting for the variability of the C282Y allele throughout Europe.…”

Reply to Delanghe, Speeckaert, and De Buyzere: “The evolutionary adaptation of hemochromatosis associated mutations during the Neolithic”

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The authors argue that our hypotheses relating the C282Y mutation to the chilly and damp climates of Europe are not supported (Heath et al, 2016). We thank the authors for taking interest in our research.

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The evolutionary adaptation of hemochromatosis associated mutations during the neolithic

“…In a recent paper (Heath, Axton, McCullough, & Harris, 2016), the spread of the C282Y allele in Europe was considered as a genetic adaptation to the chilly and damp environments of Neolithic Europe, where adequate iron was required for thermoregulation. The C282Y allele frequency has an inverse linear relationship with mean daily temperatures, an inverse linear relationship with the mean maximum temperatures, and a linear relationship with mean wet days per year.…”

“…In a recent paper (Heath, Axton, McCullough, & Harris, 2016), the spread of the C282Y allele in Europe was considered as a genetic adaptation to the chilly and damp environments of Neolithic Europe, where adequate iron was required for thermoregulation. Island has the double C282Y allele frequency than the cold and rainy Orkneys (Heath et al, 2016). These findings plead against a climate driven spread of C282Y in Europe.…”