A single gene may have helped humans develop more sweat glands to better adapt to humid climates, according to new research by Harvard University scientists.
In the study published today in Cell (1), the researchers tweaked a single amino acid in a mouse's genome and found that the animal developed more sweat glands and thicker hair. Computer models also showed that the mutation is associated with more sweat glands in the Han Chinese population and that it likely developed in China 30,000 years ago.
The study was the first to use mice to model the subtle, phenotypic effects of evolutionary beneficial mutations among humans, rather than between humans and other species, Kamberov said. The method, which draws on data from animal and computer models, may provide a new framework for identifying the genetic mutations that allow some human populations to better adapt to regional climates.
"This research has two goals: understanding how the different challenges we faced in different environments caused the diversity among human populations we see today, and how the resulting genetic differences affect our physiology," said study co-author Bruce Morgan, a molecular geneticist at Harvard and the Massachusetts General Hospital, in an email.
Understanding regional adaptations could explain why people of different ethnic backgrounds are preferentially sensitive to different diseases or have varied responses to the same treatments.
Previously, geneticists had identified only three evolutionary adaptive mutations, which are associated with malaria resistance, milk digestion, and skin pigmentation. This work is challenging because the phenotypic changes are subtle. "It's not like we're taking a sledgehammer to the genome and making big changes where we cause disease," Kamberov said.
The team chose to work with the gene variant EDAR370A because past experiments had shown that it was associated with increased scalp hair thickness and changes in teeth shape in multiple East Asian populations. Based on their results, Kamberov believes that the EDAR variant could have helped humans adapt to the humid climates possibly existing in China 30,000 years ago.
In a companion study also published today in Cell, Kamberov's mentor, Harvard computational geneticist Pardis Sabeti, and her collaborators identify additional gene variants that could have aided human evolution. Sabeti and her team used data from the 1000 Genomes Project to catalogue 412 fine-mapped genome regions, isolating 20–100 candidate variants in each. To validate the technique, the team targeted a mutation in the TLR5 gene and found that it changed the immune responses of cells exposed to bacterial proteins, a finding that suggests that the variant could protect against bacterial infections and offer a fitness advantage (2).
These studies show geneticists that they can now ask questions about the changes in genes that have made a difference to human health and reproductive success in different environments and why they are important, Morgan said.
1. Kamberov, et al. 2013. Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell 152:691–702.
2. Grossman, et al. 2013. Identifying recent adaptations in large-scale genomic data. Cell 152:703–713.