Complex signatures of selection and gene conversion in the duplicated globin genes of house mice

Jay F. Storz, Monica Baze, Jessica L. Waite, Federico G. Hoffmann, Juan C. Opazo, Jack P. Hayes

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked α-globin paralogs and two closely linked β-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two β-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbb s (which carries two identical β-globin paralogs) and Hbb d (which carries two functionally divergent β-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two β-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus β-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.

Original languageEnglish (US)
Pages (from-to)481-500
Number of pages20
JournalGenetics
Volume177
Issue number1
DOIs
StatePublished - Sep 1 2007

Fingerprint

Gene Conversion
Globins
Haplotypes
Genes
Nucleotides
Hemoglobins
South America
Genetic Selection
Linkage Disequilibrium
Glutathione
Nitric Oxide
Alleles

ASJC Scopus subject areas

  • Genetics

Cite this

Complex signatures of selection and gene conversion in the duplicated globin genes of house mice. / Storz, Jay F.; Baze, Monica; Waite, Jessica L.; Hoffmann, Federico G.; Opazo, Juan C.; Hayes, Jack P.

In: Genetics, Vol. 177, No. 1, 01.09.2007, p. 481-500.

Research output: Contribution to journalArticle

Storz, Jay F. ; Baze, Monica ; Waite, Jessica L. ; Hoffmann, Federico G. ; Opazo, Juan C. ; Hayes, Jack P. / Complex signatures of selection and gene conversion in the duplicated globin genes of house mice. In: Genetics. 2007 ; Vol. 177, No. 1. pp. 481-500.
@article{c6f391916f704efc98ab4ab087368180,
title = "Complex signatures of selection and gene conversion in the duplicated globin genes of house mice",
abstract = "Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked α-globin paralogs and two closely linked β-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two β-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbb s (which carries two identical β-globin paralogs) and Hbb d (which carries two functionally divergent β-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two β-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus β-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.",
author = "Storz, {Jay F.} and Monica Baze and Waite, {Jessica L.} and Hoffmann, {Federico G.} and Opazo, {Juan C.} and Hayes, {Jack P.}",
year = "2007",
month = "9",
day = "1",
doi = "10.1534/genetics.107.078550",
language = "English (US)",
volume = "177",
pages = "481--500",
journal = "Genetics",
issn = "0016-6731",
publisher = "Genetics Society of America",
number = "1",

}

TY - JOUR

T1 - Complex signatures of selection and gene conversion in the duplicated globin genes of house mice

AU - Storz, Jay F.

AU - Baze, Monica

AU - Waite, Jessica L.

AU - Hoffmann, Federico G.

AU - Opazo, Juan C.

AU - Hayes, Jack P.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked α-globin paralogs and two closely linked β-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two β-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbb s (which carries two identical β-globin paralogs) and Hbb d (which carries two functionally divergent β-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two β-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus β-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.

AB - Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked α-globin paralogs and two closely linked β-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two β-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbb s (which carries two identical β-globin paralogs) and Hbb d (which carries two functionally divergent β-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two β-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus β-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.

UR - http://www.scopus.com/inward/record.url?scp=35248898086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35248898086&partnerID=8YFLogxK

U2 - 10.1534/genetics.107.078550

DO - 10.1534/genetics.107.078550

M3 - Article

C2 - 17660536

AN - SCOPUS:35248898086

VL - 177

SP - 481

EP - 500

JO - Genetics

JF - Genetics

SN - 0016-6731

IS - 1

ER -