GEPHE SUMMARY Print
Entry Status
Published
GepheID
GP00000476
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Peromyscus maniculatus -low elevation
Trait State in Taxon B
Peromyscus maniculatus - high elevation
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
HBB
Synonyms
ECYT6; CD113t-C; beta-globin
Sequence Similarities
Belongs to the globin family.
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Mutation #1
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Ala62Gly; Gly72Ser; Ser128Ala; Ala135Ser
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Ala Gly 62
Authors
Storz JF; Runck AM; Sabatino SJ; Kelly JK; Ferrand N; Moriyama H; Weber RE; Fago A
Abstract
Adaptive modifications of heteromeric proteins may involve genetically based changes in single subunit polypeptides or parallel changes in multiple genes that encode distinct, interacting subunits. Here we investigate these possibilities by conducting a combined evolutionary and functional analysis of duplicated globin genes in natural populations of deer mice (Peromyscus maniculatus) that are adapted to different elevational zones. A multilocus analysis of nucleotide polymorphism and linkage disequilibrium revealed that high-altitude adaptation of deer mouse hemoglobin involves parallel functional differentiation at multiple unlinked gene duplicates: two alpha-globin paralogs on chromosome 8 and two beta-globin paralogs on chromosome 1. Differences in O(2)-binding affinity of the alternative beta-chain hemoglobin isoforms were entirely attributable to allelic differences in sensitivity to 2,3-diphosphoglycerate (DPG), an allosteric cofactor that stabilizes the low-affinity, deoxygenated conformation of the hemoglobin tetramer. The two-locus beta-globin haplotype that predominates at high altitude is associated with suppressed DPG-sensitivity (and hence, increased hemoglobin-O(2) affinity), which enhances pulmonary O(2) loading under hypoxia. The discovery that allelic differences in DPG-sensitivity contribute to adaptive variation in hemoglobin-O(2) affinity illustrates the value of integrating evolutionary analyses of sequence variation with mechanistic appraisals of protein function. Investigation into the functional significance of the deer mouse beta-globin polymorphism was motivated by the results of population genetic analyses which revealed evidence for a history of divergent selection between elevational zones. The experimental measures of O(2)-binding properties corroborated the tests of selection by demonstrating a functional difference between the products of alternative alleles.
Mutation #2
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Ala62Gly; Gly72Ser; Ser128Ala; Ala135Ser
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Gly Ser 72
Authors
Storz JF; Runck AM; Sabatino SJ; Kelly JK; Ferrand N; Moriyama H; Weber RE; Fago A
Abstract
Adaptive modifications of heteromeric proteins may involve genetically based changes in single subunit polypeptides or parallel changes in multiple genes that encode distinct, interacting subunits. Here we investigate these possibilities by conducting a combined evolutionary and functional analysis of duplicated globin genes in natural populations of deer mice (Peromyscus maniculatus) that are adapted to different elevational zones. A multilocus analysis of nucleotide polymorphism and linkage disequilibrium revealed that high-altitude adaptation of deer mouse hemoglobin involves parallel functional differentiation at multiple unlinked gene duplicates: two alpha-globin paralogs on chromosome 8 and two beta-globin paralogs on chromosome 1. Differences in O(2)-binding affinity of the alternative beta-chain hemoglobin isoforms were entirely attributable to allelic differences in sensitivity to 2,3-diphosphoglycerate (DPG), an allosteric cofactor that stabilizes the low-affinity, deoxygenated conformation of the hemoglobin tetramer. The two-locus beta-globin haplotype that predominates at high altitude is associated with suppressed DPG-sensitivity (and hence, increased hemoglobin-O(2) affinity), which enhances pulmonary O(2) loading under hypoxia. The discovery that allelic differences in DPG-sensitivity contribute to adaptive variation in hemoglobin-O(2) affinity illustrates the value of integrating evolutionary analyses of sequence variation with mechanistic appraisals of protein function. Investigation into the functional significance of the deer mouse beta-globin polymorphism was motivated by the results of population genetic analyses which revealed evidence for a history of divergent selection between elevational zones. The experimental measures of O(2)-binding properties corroborated the tests of selection by demonstrating a functional difference between the products of alternative alleles.
Mutation #3
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Ala62Gly; Gly72Ser; Ser128Ala; Ala135Ser
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Ser Ala 128
Authors
Storz JF; Runck AM; Sabatino SJ; Kelly JK; Ferrand N; Moriyama H; Weber RE; Fago A
Abstract
Adaptive modifications of heteromeric proteins may involve genetically based changes in single subunit polypeptides or parallel changes in multiple genes that encode distinct, interacting subunits. Here we investigate these possibilities by conducting a combined evolutionary and functional analysis of duplicated globin genes in natural populations of deer mice (Peromyscus maniculatus) that are adapted to different elevational zones. A multilocus analysis of nucleotide polymorphism and linkage disequilibrium revealed that high-altitude adaptation of deer mouse hemoglobin involves parallel functional differentiation at multiple unlinked gene duplicates: two alpha-globin paralogs on chromosome 8 and two beta-globin paralogs on chromosome 1. Differences in O(2)-binding affinity of the alternative beta-chain hemoglobin isoforms were entirely attributable to allelic differences in sensitivity to 2,3-diphosphoglycerate (DPG), an allosteric cofactor that stabilizes the low-affinity, deoxygenated conformation of the hemoglobin tetramer. The two-locus beta-globin haplotype that predominates at high altitude is associated with suppressed DPG-sensitivity (and hence, increased hemoglobin-O(2) affinity), which enhances pulmonary O(2) loading under hypoxia. The discovery that allelic differences in DPG-sensitivity contribute to adaptive variation in hemoglobin-O(2) affinity illustrates the value of integrating evolutionary analyses of sequence variation with mechanistic appraisals of protein function. Investigation into the functional significance of the deer mouse beta-globin polymorphism was motivated by the results of population genetic analyses which revealed evidence for a history of divergent selection between elevational zones. The experimental measures of O(2)-binding properties corroborated the tests of selection by demonstrating a functional difference between the products of alternative alleles.
Mutation #4
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Ala62Gly; Gly72Ser; Ser128Ala; Ala135Ser
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Ala Ser 135
Authors
Storz JF; Runck AM; Sabatino SJ; Kelly JK; Ferrand N; Moriyama H; Weber RE; Fago A
Abstract
Adaptive modifications of heteromeric proteins may involve genetically based changes in single subunit polypeptides or parallel changes in multiple genes that encode distinct, interacting subunits. Here we investigate these possibilities by conducting a combined evolutionary and functional analysis of duplicated globin genes in natural populations of deer mice (Peromyscus maniculatus) that are adapted to different elevational zones. A multilocus analysis of nucleotide polymorphism and linkage disequilibrium revealed that high-altitude adaptation of deer mouse hemoglobin involves parallel functional differentiation at multiple unlinked gene duplicates: two alpha-globin paralogs on chromosome 8 and two beta-globin paralogs on chromosome 1. Differences in O(2)-binding affinity of the alternative beta-chain hemoglobin isoforms were entirely attributable to allelic differences in sensitivity to 2,3-diphosphoglycerate (DPG), an allosteric cofactor that stabilizes the low-affinity, deoxygenated conformation of the hemoglobin tetramer. The two-locus beta-globin haplotype that predominates at high altitude is associated with suppressed DPG-sensitivity (and hence, increased hemoglobin-O(2) affinity), which enhances pulmonary O(2) loading under hypoxia. The discovery that allelic differences in DPG-sensitivity contribute to adaptive variation in hemoglobin-O(2) affinity illustrates the value of integrating evolutionary analyses of sequence variation with mechanistic appraisals of protein function. Investigation into the functional significance of the deer mouse beta-globin polymorphism was motivated by the results of population genetic analyses which revealed evidence for a history of divergent selection between elevational zones. The experimental measures of O(2)-binding properties corroborated the tests of selection by demonstrating a functional difference between the products of alternative alleles.
RELATED GEPHE
Related Haplotypes
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COMMENTS
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