Biology & Philosophy

, Volume 25, Issue 2, pp 183–201 | Cite as

The mystery of the mystery of common genetic diseases

  • Sean A. VallesEmail author


Common monogenic genetic diseases, ones that have unexpectedly high frequencies in certain populations, have attracted a great number of conflicting evolutionary explanations. This paper will attempt to explain the mystery of why two particularly extensively studied common genetic diseases, Tay Sachs disease and cystic fibrosis, remain evolutionary mysteries despite decades of research. I review the most commonly cited evolutionary processes used to explain common genetic diseases: reproductive compensation, random genetic drift (in the context of founder effect), and especially heterozygote advantage. The latter process has drawn a particularly large amount of attention, having so successfully explained the elevated frequency of sickle cell anemia in malaria-endemic areas. However, the empirical evidence for heterozygote advantage in other common genetic diseases is quite weak. I introduce and illustrate the significance of a hierarchy of genetic disease phenomena found within the genetic disease explanations, which include the phenomena: single mutation variants of a common genetic disease, single genetic diseases, and classes of diseases with related phenotypic effects. I demonstrate that some of the confusion over the explanations of common genetic diseases can be traced back to confusions over which phenomena are being explained. I proceed to briefly evaluate the existing evidence for two common human genetic diseases: Tay Sachs disease and cystic fibrosis. The above considerations will ultimately shed light on why these diseases’ evolutionary explanations remain so deeply unresolved after so such a great volume of research.


Cystic fibrosis Founder effect Genetic disease Heterozygote advantage Random genetic drift Reproductive compensation Tay Sachs disease 



I am deeply grateful for the many helpful suggestions offered by the Indiana University Biology Studies Reading Group. I would like to especially thank Elisabeth Lloyd for her paramount patience and wisdom throughout the writing and revising of the paper, as well as Michael Wade for his detailed and insightful advice on both the biology and the philosophy. I am also very grateful for the invaluable comments and suggestions provided by Kim Sterelny and an anonymous reviewer.


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Indiana University History and Philosophy of Science DepartmentBloomingtonUSA

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