Convergent neofunctionalization by positive Darwinian selection after ancient recurrent duplications of the xanthine dehydrogenase gene

被引:71
作者
Rodríguez-Trelles, F
Tarrío, R
Ayala, FJ [1 ]
机构
[1] Univ Calif Irvine, Dept Ecol & Evolut Biol, Irvine, CA 92697 USA
[2] Univ Santiago de Compostela, Unidad Med Mol, Inst Galego Oftalmoloxia, Hosp Clin Univ, E-15706 Santiago, Spain
关键词
D O I
10.1073/pnas.1835646100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Gene duplication is a primary source of molecular substrate for the emergence of evolutionary novelties. The chances for redundant gene sequences to evolve new functions are small compared with the probability that the copies become disabled by deleterious mutations. Functional divergence after gene duplication can result in two alternative evolutionary fates: one copy acquires a novel function (neofunctionalization), or each copy adopts part of the tasks of their parental gene (subfunctionalization). The relative prevalence of each outcome is unknown. Similarly unknown is the relative importance of positive selection versus random fixation of neutral mutations. Aldehyde oxidase (Ao) and xanthine dehydrogenase (Xdh) genes encode two complex members of the xanthine oxidase family of molybdo-flavoenzymes that carry different functions. Ao is known to have originated from a duplicate of an Xdh gene in eukaryotes, before the origin of multicellularity. We show that (i) Ao evolved independently twice from two different Xdh paralogs, the second time in the chordates, before the diversification of vertebrates; (h) after each duplication, the Ao duplicate underwent a period of rapid evolution during which identical sites across the two molecules, involving the flavin adenine dinucleotide and substrate-binding pockets, were subjected to intense positive Darwinian selection; and (iii) the second Ao gene likely endured two periods of redundancy, initially as a duplicate of Xdh and later as a functional equivalent of the old Ao, which is currently absent from the vertebrate genome. Caution is appropriate in structural genomics when using sequence similarity for assigning protein function.
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页码:13413 / 13417
页数:5
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