title: Adaptive evolution and divergence of SERPINB3: a young duplicate in great Apes.
abstract: A series of duplication events led to an expansion of clade B Serine Protease Inhibitors (SERPIN), currently displaying a large repertoire of functions in vertebrates. Accordingly, the recent duplicates SERPINB3 and B4 located in human 18q21.3 SERPIN cluster control the activity of different cysteine and serine proteases, respectively. Here, we aim to assess SERPINB3 and B4 coevolution with their target proteases in order to understand the evolutionary forces shaping the accelerated divergence of these duplicates. Phylogenetic analysis of primate sequences placed the duplication event in a Hominoidae ancestor (∼30 Mya) and the emergence of SERPINB3 in Homininae (∼9 Mya). We detected evidence of strong positive selection throughout SERPINB4/B3 primate tree and target proteases, cathepsin L2 (CTSL2) and G (CTSG) and chymase (CMA1). Specifically, in the Homininae clade a perfect match was observed between the adaptive evolution of SERPINB3 and cathepsin S (CTSS) and most of sites under positive selection were located at the inhibitor/protease interface. Altogether our results seem to favour a coevolution hypothesis for SERPINB3, CTSS and CTSL2 and for SERPINB4 and CTSG and CMA1. A scenario of an accelerated evolution driven by host-pathogen interactions is also possible since SERPINB3/B4 are potent inhibitors of exogenous proteases, released by infectious agents. Finally, similar patterns of expression and the sharing of many regulatory motifs suggest neofunctionalization as the best fitted model of the functional divergence of SERPINB3 and B4 duplicates.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Gomes
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Patrícia I
authors.initials: PI
authors.lastname: Marques
authors.affiliation: National Health Institute Doutor Ricardo Jorge (INSA), Lisboa, Portugal.
authors.forename: Rune
authors.initials: R
authors.lastname: Matthiesen
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Seixas
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D053818:Chymases / Q000737:chemistry / Q000145:classification / Q000235:genetics; D019143:Evolution, Molecular; D015186:Hominidae; D010802:Phylogeny; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry* / Q000145:classification / Q000235:genetics*
chemical_list: D015843:Serpins; D002403:Cathepsins; D053818:Chymases