Mice living at high altitudes in the American West carry a genetic variant that increases their heart rate, helping them cope with the low oxygen levels that occur at high elevations. Rena Schweizer of the University of Montana and colleagues report these findings in a new study published 30th October in PLOS Genetics.
Mountains and plateaus are challenging environments for animals due to cold temperatures and reduced oxygen concentrations in the air. In the current study, researchers investigated genetic changes in North American deer mice that are linked to physiological changes that help them cope with too little oxygen. By sequencing samples from 100 mice living at different elevations, they identified a variant of the gene Epas1, which is much more common in deer mice living at high altitudes than in lowland populations. Mice with the "highland" version of the gene have a higher heart rate when exposed to low oxygen levels, which increases the amount of oxygen circulating in the bloodstream.
The new study is the first to show a relationship between naturally occurring genetic variations in Epas1 and changes to the heart rate, and suggests that Epas1 may aid long-term survival of high-altitude deer mice. Epas1 has also been implicated in respiratory and cardiovascular adaptations in Tibetans living at high altitudes on the Qinghai-Tibetan plateau, when compared to closely related lowland Han Chinese populations.
"Our study addresses a really important question about how adaptation occurs on complex physiology that is controlled by multiple interacting system," said author Rena Schweizer. "Epas1 may aid long-term survival of high-altitude deer mice, and is a case by which a relatively simple genetic change in a control gene may alter adaptive traits. Our future work on Epas1 is aimed at exploring the specific mechanisms by which the protein-altering mutation affects heart rate, and whether the mutation affects any other traits that we did not previously measure."
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Peer-reviewed; Observational study; Animals
In your coverage please use this URL to provide access to the freely available article in PLOS Genetics: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008420
Citation: Schweizer RM, Velotta JP, Ivy CM, Jones MR, Muir SM, Bradburd GS, et al. (2019) Physiological and genomic evidence that selection on the transcription factor Epas1 has altered cardiovascular function in high-altitude deer mice. PLoS Genet 15(10): e1008420. https://doi.org/10.1371/journal.pgen.1008420
Funding: Funding support was provided by the National Science Foundation (https://nsf.gov/; OIA 1736249 to ZAC and JFS; IOS 1755411 to ZAC and GRS; Postdoctoral Research Fellowship in Biology 1612859 to RMS), the National Heart, Lung, and Blood Institute of the National Institutes of Health (https://www.nhlbi.nih.gov/; HL087216 to JFS; Research Service Award Fellow to JPV, Grant Number 1F32HL136124-01), and the Natural Sciences and Engineering Research Council of Canada (http://www.nserc-crsng.gc.ca/index_eng.asp; Discovery Grant 418202-2012 to GRS; Postgraduate Scholarship to CMI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Journal
PLoS Genetics