| Figures/TablesFigures/Tables | ReferencesReferences
Summary
Chromosomal stability is safeguarded by a mitotic check
point, of which BUB1 and Mad3/BUBR1 are core com
ponents. These
paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1
paralogous
pairs arose by nine inde
pendent gene du
plications throughout evolution, followed by
parallel subfunctionalization in which
preservation of the ancestral, amino-terminal KEN box or kinase domain was mutually exclusive. In one exce
ption, vertebrate BUBR1¡ªdefined by the KEN box¡ª
preserved the kinase domain but allowed nonconserved degeneration of catalytic motifs. Although BUBR1 evolved to a ty
pical
pseudokinase in some vertebrates, it retained the catalytic triad in humans. However, we show that
putative catalysis by human BUBR1 is dis
pensable for error-free chromosome segregation. Instead, residues that interact with ATP in conventional kinases are essential for conformational stability in BUBR1. We
pro
pose that
parallel evolution of BUBR1 orthologs rendered its kinase function dis
pensable in vertebrates,
producing an unusual, triad-containing
pseudokinase.
Video Abstract
