title: Repeated evolution of chimeric fusion genes in the β-globin gene family of laurasiatherian mammals.
abstract: The evolutionary fate of chimeric fusion genes may be strongly influenced by their recombinational mode of origin and the nature of functional divergence between the parental genes. In the β-globin gene family of placental mammals, the two postnatally expressed δ- and β-globin genes (HBD and HBB, respectively) have a propensity for recombinational exchange via gene conversion and unequal crossing-over. In the latter case, there are good reasons to expect differences in retention rates for the reciprocal HBB/HBD and HBD/HBB fusion genes due to thalassemia pathologies associated with the HBD/HBB "Lepore" deletion mutant in humans. Here, we report a comparative genomic analysis of the mammalian β-globin gene cluster, which revealed that chimeric HBB/HBD fusion genes originated independently in four separate lineages of laurasiatherian mammals: Eulipotyphlans (shrews, moles, and hedgehogs), carnivores, microchiropteran bats, and cetaceans. In cases where an independently derived "anti-Lepore" duplication mutant has become fixed, the parental HBD and/or HBB genes have typically been inactivated or deleted, so that the newly created HBB/HBD fusion gene is primarily responsible for synthesizing the β-type subunits of adult and fetal hemoglobin (Hb). Contrary to conventional wisdom that the HBD gene is a vestigial relict that is typically inactivated or expressed at negligible levels, we show that HBD-like genes often encode a substantial fraction (20-100%) of β-chain Hbs in laurasiatherian taxa. Our results indicate that the ascendancy or resuscitation of genes with HBD-like coding sequence requires the secondary acquisition of HBB-like promoter sequence via unequal crossing-over or interparalog gene conversion.
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gaudry
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University.
authors.forename: Gary Tyler
authors.initials: GT
authors.lastname: Butts
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Campbell
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State UniversityInstitute for Genomics, Biocomputing and Biotechnology, Mississippi State University federico.g.hoffmann@gmail.com.
authors.forename: Federico G
authors.initials: FG
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D002685:Chiroptera / Q000235:genetics; D019143:Evolution, Molecular; D005785:Gene Conversion; D018507:Gene Expression Regulation, Developmental; D050939:Gene Fusion; D006801:Humans; D008322:Mammals / Q000235:genetics*; D005810:Multigene Family; D010802:Phylogeny; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins
keywords: Laurasiatheria; concerted evolution; gene conversion; gene duplication; gene family evolution; hemoglobin; β-globin