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"Sloan, Angela M."

 
 
Opazo, Juan C.; Sloan, Angela M.; Campbell, Kevin L.; Storz, Jay F. (detail)
   
2009
Origin and ascendancy of a chimeric fusion gene: The beta/delta-Globin gene of paenungulate mammals.
Molecular Biology and Evolution 26(7): 1469-1478. 7 figs. DOI: 10.1093/molbev/msp064. July 2009.
–ABSTRACT: The ?-globin gene (HBD) of eutherian mammals exhibits a propensity for recombinational exchange with the closely linked ?-globin gene (HBB) and has been independently converted by the HBB gene in multiple lineages. Here we report the presence of a chimeric ?/? 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 ?/? 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 ?/? fusion gene supplanted the parental HBB gene and is therefore solely responsible for synthesizing the ?-chain subunits of adult hemoglobin. A phylogenetic survey of ?-like globin genes in afrotherian and xenarthran mammals revealed that the origin of the chimeric ?/? 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 ?/? fusion genes (which occur on an anti-Lepore chromosome) have been fixed in a number of mammalian lineages, whereas the reciprocal ?/? 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.

Daryl P. Domning, Research Associate, Department of Paleobiology, National Museum of Natural History, Smithsonian Institution, Washington, D.C. 20560, and Laboratory of Evolutionary Biology, Department of Anatomy, College of Medicine, Howard University, Washington, D.C. 20059.
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