Origin and Ascendancy of a Chimeric Fusion Gene: The  / -Globin Gene of Paenungulate Mammals

Abstract

The delta-globin gene (HBD) of eutherian mammals exhibits a propensity for recombinational exchange with the closely linked beta-globin gene (HBB) and has been independently converted by the HBB gene in multiple lineages. Here we report the presence of a chimeric beta/delta fusion gene in the African elephant (Loxodonta africana) that was created by unequal crossing-over between misaligned HBD and HBB paralogs. The recombinant chromosome that harbors the beta/delta fusion gene in elephants is structurally similar to the "anti-Lepore" duplication mutant of humans (the reciprocal exchange product of the hemoglobin Lepore deletion mutant). However, the situation in the African elephant is unique in that the chimeric beta/delta fusion gene supplanted the parental HBB gene and is therefore solely responsible for synthesizing the beta-chain subunits of adult hemoglobin. A phylogenetic survey of beta-like globin genes in afrotherian and xenarthran mammals revealed that the origin of the chimeric beta/delta fusion gene and the concomitant inactivation of the HBB gene predated the radiation of "Paenungulata," a clade of afrotherian mammals that includes three orders: Proboscidea (elephants), Sirenia (dugongs and manatees), and Hyracoidea (hyraxes). The reduced fitness of the human Hb Lepore deletion mutant helps to explain why independently derived beta/delta fusion genes (which occur on an anti-Lepore chromosome) have been fixed in a number of mammalian lineages, whereas the reciprocal delta/beta fusion gene (which occurs on a Lepore chromosome) has yet to be documented in any nonhuman mammal. This illustrates how the evolutionary fates of chimeric fusion genes can be strongly influenced by their recombinational mode of origin.

Altitudinal Variation at Duplicated β-Globin Genes in Deer Mice: Effects of Selection, Recombination, and Gene Conversion

“…We assumed that gene conversion affected only the selected loci (which were stand-ins for the two HBB paralogs) and that allelic and nonallelic gene conversion occur at equal rates. The former assumption is justifed by the well-documented pattern in the a-and b-globin gene families of mammals that nonallelic gene conversion is almost exclusively restricted to coding sequence (Storz et al 2007bHoffmann et al 2008a,b;Opazo et al 2008Opazo et al , 2009Runck et al 2009Runck et al , 2010. We also assume that the conversion tract spans the entire sequence of the recipient gene, which again is consistent with empirical data for mammalian b-globin genes (Borg et al 2009).…”

MosaicFinder: identification of fused gene families in sequence similarity networks

“…The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. fused globins have been reported, occasionally supplanting the parental gene form, as was the case for the fusion of /Á globin, before the radiation of Paenungulata (the clade containing elephants, dugongs and manatees and hyraxes) (Opazo et al, 2009). Similarly, some of the toxins exploited by sea anemones to paralyse their preys have evolved by gene fusion, as they improved the transcript stability and secretion of these toxins (Moran et al, 2009).…”

Gene duplication, genome duplication, and the functional diversification of vertebrate globins

“…Multiple rounds of duplication and divergence have produced diverse repertoires of α- and β-like globin genes that are ontogenetically regulated such that functionally distinct Hb isoforms are expressed during different stages of prenatal development and postnatal life (Alev et al 2009; Brittain 2002; Hardison 2001; Hoffmann et al 2008a,b; Opazo et al 2008a,b, 2009; Storz et al 2011b). Surprisingly, however, phylogenetic analyses of the α- and β-globin gene families have revealed that genes with similar stage-specific expression patterns in different species do not necessarily represent 1:1 orthologs that were inherited from a common ancestor (Czelusniak et al 1982; Hoffmann et al 2010b; Opazo et al 2008a; Storz et al 2011a; Opazo et al 2012).…”