GEPHE SUMMARY Print
Gephebase Gene
Entry Status
Published
GepheID
GP00002062
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
deer mice in lowlands
Trait State in Taxon B
deer mice native to the Rocky Mountain highlands
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Common Name
North American deer mouse
Synonyms
North American deer mouse; Peromyscus maniculatus (Wagner, 1845); MSB Mamm 74965; MSB:collector:Mamm:74965; Peromyscus maniculatis
Rank
species
Lineage
Show more ... eostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Cricetidae; Neotominae; Peromyscus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
North American deer mouse
Synonyms
North American deer mouse; Peromyscus maniculatus (Wagner, 1845); MSB Mamm 74965; MSB:collector:Mamm:74965; Peromyscus maniculatis
Rank
species
Lineage
Show more ... eostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Cricetidae; Neotominae; Peromyscus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
EPAS1
Synonyms
HLF; MOP2; ECYT4; HIF2A; PASD2; bHLHe73; BHLHE73
Sequence Similarities
-
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
-
Molecular Details of the Mutation
non-synonymous polymorphism located at site 755 in the 14th exon that changes threonine to methionine Thr755Met
Experimental Evidence
Taxon A Taxon B Position
Codon ACG ATG -
Amino-acid Thr Met 755
Authors
Schweizer RM; Velotta JP; Ivy CM; Jones MR; Muir SM; Bradburd GS; Storz JF; Scott GR; et al. ... show more
Abstract
Evolutionary adaptation to extreme environments often requires coordinated changes in multiple intersecting physiological pathways, but how such multi-trait adaptation occurs remains unresolved. Transcription factors, which regulate the expression of many genes and can simultaneously alter multiple phenotypes, may be common targets of selection if the benefits of induced changes outweigh the costs of negative pleiotropic effects. We combined complimentary population genetic analyses and physiological experiments in North American deer mice (Peromyscus maniculatus) to examine links between genetic variation in transcription factors that coordinate physiological responses to hypoxia (hypoxia-inducible factors, HIFs) and multiple physiological traits that potentially contribute to high-altitude adaptation. First, we sequenced the exomes of 100 mice sampled from different elevations and discovered that several SNPs in the gene Epas1, which encodes the oxygen sensitive subunit of HIF-2α, exhibited extreme allele frequency differences between highland and lowland populations. Broader geographic sampling confirmed that Epas1 genotype varied predictably with altitude throughout the western US. We then discovered that Epas1 genotype influences heart rate in hypoxia, and the transcriptomic responses to hypoxia (including HIF targets and genes involved in catecholamine signaling) in the heart and adrenal gland. Finally, we used a demographically-informed selection scan to show that Epas1 variants have experienced a history of spatially varying selection, suggesting that differences in cardiovascular function and gene regulation contribute to high-altitude adaptation. Our results suggest a mechanism by which Epas1 may aid long-term survival of high-altitude deer mice and provide general insights into the role that highly pleiotropic transcription factors may play in the process of environmental adaptation.
Additional References
RELATED GEPHE
Related Haplotypes
No matches found.
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