NSF Award
2419584
The mismatch hypothesis states that past lifestyles selected for genes that are now, in modern urbanized groups, detrimental to human health. The presence of these past-selected genes in modern human populations account for the current surge of non-communicable diseases such as obesity, type-II diabetes, and cardiovascular disease. To date, most studies that test this idea are limited because they compare genetically distinct groups. This dissertation project addresses this issue by focusing on a group of individuals that share a similar genetic background but live in environments that are a “match” (subsistence-level) or a “mismatch” (urban) to their previous lifestyle. The study informs genome-environment interactions in humans, human adaptation, and health, as well as the tempo of evolution in modern human populations. The study involves the participating community through multiple strategies and uses community-driven techniques in the production of public information. The study provides training opportunities for graduate and undergraduate students of diverse backgrounds and deepens the interaction and communication among researchers interested in this topic. <br/><br/>A total of ~700 participants, with approximately even sex-ratios, are included in the study. A composite continuous lifestyle index (traditional-to-non-traditional) is calculated for each individual based on data collected through structured interviews. Putatively beneficial genomic sites are identified using whole genome sequencing (WGS). Signatures of past-selection are recognized using selection statistics that examine patterns of allele frequency and/or haplotype homozygosity. These analyses include population branch statistics (PBS), integrated haplotype score (iHS), and cross population extended haplotype homozygosity score (XP-EHH). Two outgroups are used to calculate allele-frequency-changes in each single nucleotide polymorphism (SNP). RNA extracted from the participants is analyzed with mRNA-seq analyses. The expression of the identified previously-selected genes will be assessed to characterize genotype-environment interactions and evaluated in relation to lifestyle-associated diseases.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
