Biological Sciences Division
Published September 11, 2023 | Version v1
Journal article Open

Applying an evolutionary mismatch framework to understand disease susceptibility

Creators

  • 1. Vanderbilt University
  • 2. Cornell University
  • 3. University of Chicago
  • 4. New York University
  • 5. Stanford University
  • 6. Harvard University
  • 7. Institute of Primate Research
  • 8. University of Utah
  • 9. Universiti Malaya
  • 10. Stony Brook University
  • 11. Ministry of Health Laikipia County
  • 12. University of California Los Angeles
  • 13. Pennsylvania State University
  • 14. Duke University
  • 15. Arizona State University
  • 16. Baylor University
  • 17. University of Calgary
  • 18. University of New Mexico
  • 19. University of California Santa Barbara
  • 20. Princeton University

Description

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 in partnership 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.

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Additional details

Identifiers

DOI
10.1371/journal.pbio.3002311
Other
oai:uchicago.tind.io:8195

Funding

Canadian Institute for Advanced Research
Searle Scholars Program
National Institutes of Health
NIGMS - R35-GM147267
National Institutes of Health
NIEHS R01ES029929
National Institutes of Health
NIGMS R35-GM124881

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine