Applying an evolutionary mismatch framework to understand disease susceptibility

Amanda J. Lea, Andrew G. Clark, Andrew W. Dahl, Orrin Devinsky, Angela R. Garcia, Christopher D. Golden, Joseph Kamau, Thomas S. Kraft, Yvonne A.L. Lim, Dino J. Martins, Donald Mogoi, Päivi Pajukanta, George H. Perry, Herman Pontzer, Benjamin C. Trumble, Samuel S. Urlacher, Vivek V. Venkataraman, Ian J. Wallace, Michael Gurven, Daniel E. LiebermanJulien F. Ayroles

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease and type 2 diabetes are among a long list of "lifestyle"diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched"and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment"(GxE) interactions, with different health effects in "ancestral"versus "modern"environments. To identify such loci, we advocate for combining genomic tools with partnerships with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched"to "mismatched"spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Original languageEnglish (US)
Article numbere3002311
JournalPLoS biology
Issue number9 September
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience
  • General Agricultural and Biological Sciences


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