Intraspecific Polymorphism, Interspecific Divergence, and the Origins of Function-Altering Mutations in Deer Mouse Hemoglobin

Authors

Chandrasekhar Natarajan, University of Nebraska-LincolnFollow
Federico G. Hoffmann, Mississippi State University
Hayley C. Lanier, University of Wyoming
Cole J. Wolf, University of Illinois at Urbana-Champaign
Zachary A. Cheviron, University of Illinois at Urbana-Champaign
Matthew L. Spangler, University of Nebraska-LincolnFollow
Roy E. Weber, Aarhus University
Angela Fago, Aarhus University
Jay F. Storz, University of Nebraska - LincolnFollow

ORCID IDs

Matthew L. Spangler

Document Type

Article

Date of this Version

2015

Citation

Mol. Biol. Evol. 32(4):978–997

Comments

Copyright The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Abstract

Major challenges for illuminating the genetic basis of phenotypic evolution are to identify causative mutations, to quantify their functional effects, to trace their origins as new or preexisting variants, and to assess the manner in which segregating variation is transduced into species differences. Here, we report an experimental analysis of genetic variation in hemoglobin (Hb) function within and among species of Peromyscus mice that are native to different elevations. A multilocus survey of sequence variation in the duplicated HBA and HBB genes in Peromyscus maniculatus revealed that function-altering amino acid variants are widely shared among geographically disparate populations

from different elevations, and numerous amino acid polymorphisms are also shared with closely related species. Variation in Hb-O2 affinity within and among populations of P. maniculatus is attributable to numerous amino acid mutations that have individually small effects. One especially surprising feature of the Hb polymorphism in P. maniculatus is that an appreciable fraction of functional standing variation in the two transcriptionally active HBA paralogs is attributable to recurrent gene conversion from a tandemly linked HBA pseudogene. Moreover, transpecific polymorphism in the duplicated HBA genes is not solely attributable to incomplete lineage sorting or introgressive hybridization; instead, it is mainly attributable to recurrent interparalog gene conversion that has occurred independently in different species. Partly as a result of concerted evolution between tandemly duplicated globin genes, the same amino acid changes that contribute to variation in Hb function within P. maniculatus also contribute to divergence in Hb function among different species of Peromyscus. In the case of function-altering Hb mutations in Peromyscus, there is no qualitative or quantitative distinction between segregating variants within species and fixed differences between species.