title: Modes of evolution in the protease and kringle domains of the plasminogen-prothrombin family.
abstract: Phylogenetic analysis of protease domains of the vertebrate plasminogen-prothrombin family revealed two major subfamilies: (1) a subfamily containing macrophage-stimulating protein (MSP), hepatocyte growth factor (HGF), plasminogen, and apolipoprotein(a) (APOA); and (2) a subfamily containing prothrombin, HGF activator, and plasminogen activators. There was evidence that these two subfamilies diverged prior to the divergence of amphibians and amniotes. The phylogeny indicated a close relationship of APOA from the European hedgehog, rhesus monkey, and human with plasminogen. Phylogenetic analysis of repeated kringle domains supported the hypothesis that APOA evolved independently in hedgehog and primates through numerous duplications of different kringle domains of the ancestral plasminogen. Phylogenies of kringle domains revealed two modes of evolution: (1) a conservative mode, whereby duplication of kringle domains occurred prior to cladogenesis and the same kringle structure has been maintained in different lineages (exemplified by plasminogen and prothrombin); and (2) a concerted mode, whereby kringle domains have duplicated since cladogenesis and thus orthologous relationships do not exist between kringles of different lineages (exemplified by APOA).
authors.affiliation: Department of Biology and Institute of Molecular Evolutionary Genetics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Hughes
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D018082:Kringles / Q000235:genetics*; D010802:Phylogeny; D010958:Plasminogen / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D011516:Prothrombin / Q000737:chemistry* / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D011516:Prothrombin; D010958:Plasminogen; D010450:Endopeptidases