Comparative genomics of canine hemoglobin genes reveals primacy of beta subunit delta in adult carnivores
Autor: | Sara Zaldívar-López, C. Guillermo Couto, Carlos E. Alvarez, Isain Zapata, Elise Fiala, Jennie L. Rowell |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
HBH HBD Locus (genetics) beta-Globins Chimerism Canine Evolution Molecular Hemoglobins 03 medical and health sciences Euarchontoglires Dogs 0302 clinical medicine alpha-Globins Genetics Animals Humans Hemoglobin Globin Gene conversion Promoter Regions Genetic Protein Structure Quaternary Gene Phylogeny Comparative genomics Comparative Genomic Hybridization Base Sequence biology biology.organism_classification Laurasiatheria 030104 developmental biology Haplotypes Genetic Loci Multigene Family HBB DNA microarray 030217 neurology & neurosurgery Research Article Biotechnology |
Zdroj: | BMC Genomics |
ISSN: | 1471-2164 |
DOI: | 10.1186/s12864-017-3513-0 |
Popis: | Background The main function of hemoglobin (Hb) is to transport oxygen in the circulation. It is among the most highly studied proteins due to its roles in physiology and disease, and most of our understanding derives from comparative research. There is great diversity in Hb gene evolution in placental mammals, mostly in the repertoire and regulation of the β-globin subunits. Dogs are an ideal model in which to study Hb genes because: 1) they are members of Laurasiatheria, our closest relatives outside of Euarchontoglires (including primates, rodents and rabbits), 2) dog breeds are isolated populations with their own Hb-associated genetics and diseases, and 3) their high level of health care allows for development of biomedical investigation and translation. Results We established that dogs have a complement of five α and five β-globin genes, all of which can be detected as spliced mRNA in adults. Strikingly, HBD, the allegedly-unnecessary adult β-globin protein in humans, is the primary adult β-globin in dogs and other carnivores; moreover, dogs have two active copies of the HBD gene. In contrast, the dominant adult β-globin of humans, HBB, has high sequence divergence and is expressed at markedly lower levels in dogs. We also showed that canine HBD and HBB genes are complex chimeras that resulted from multiple gene conversion events between them. Lastly, we showed that the strongest signal of evolutionary selection in a high-altitude breed, the Bernese Mountain Dog, lies in a haplotype block that spans the β-globin locus. Conclusions We report the first molecular genetic characterization of Hb genes in dogs. We found important distinctions between adult β-globin expression in carnivores compared to other members of Laurasiatheria. Our findings are also likely to raise new questions about the significance of human HBD. The comparative genomics of dog hemoglobin genes sets the stage for diverse research and translation. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3513-0) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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