Modes of evolution in the protease and kringle domains of the plasminogen-prothrombin family

Phylogenetic analysis of protease domains of the vertebrate plasminogen-pro thrombin family revealed two major subfamilies: (1) a subfamily containing macrophage-stimulating protein (MSP), hepatocyte growth factor (HGF), plasm inogen, and apolipoprotein(a) (APOA); and (2) a subfamily containing prothr ombin, HGF activator, and plasminogen activators. There was evidence that t hese two subfamilies diverged prior to the divergence of amphibians and amn iotes. The phylogeny indicated a close relationship of APOA from the Europe an hedgehog, rhesus monkey, and human with plasminogen. Phylogenetic analys is of repeated kringle domains supported the hypothesis that APOA evolved i ndependently in hedgehog and primates through numerous duplications of diff erent kringle domains of the ancestral plasminogen. Phylogenies of kringle domains revealed two modes of evolution: (1) a conservative mode, whereby d uplication of kringle domains occurred prior to cladogenesis and the same k ringle structure has been maintained in different lineages (exemplified by plasminogen and prothrombin); and (2) a concerted mode, whereby kringle dom ains have duplicated since cladogenesis and thus orthologous relationships do not exist between kringles of different lineages (exemplified by APOA). (C) 2000 Academic Press.