Complex Signatures of Selection and Gene Conversion in the Duplicated Globin Genes of House Mice

Authors

Jay F. Storz, University of Nebraska - LincolnFollow
Monica Baze, University of Nevada, Reno
Jessica L. Waite, University of Nebraska - Lincoln
Federico G. Hoffmann, University of Nebraska - LincolnFollow
Juan C. Opazo, University of Nebraska - Lincoln
Jack P. Hayes, University of Nevada, Reno

Date of this Version

9-2007

Comments

Published in Genetics, Vol. 177, 481-500, September 2007, Copyright © 2007 doi:10.1534/genetics.107.078550
Copyright 2007 The Genetics Society of America.
Since the GSA does not permit archiving of their copyrighted content, the link will take you to the open-access version on their website, @ http://www.genetics.org/cgi/content/abstract/177/1/481 [abstract page with links]; the full-text PDF file is @ http://www.genetics.org/cgi/reprint/177/1/481

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 Hbb^s 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 Hbb^d 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.