title: Evolution of C, D and S-type cystatins in mammals: an extensive gene duplication in primates.
abstract: Cystatins are a family of inhibitors of cysteine peptidases that comprises the salivary cystatins (D and S-type cystatins) and cystatin C. These cystatins are encoded by a multigene family (CST3, CST5, CST4, CST1 and CST2) organized in tandem in the human genome. Their presence and functional importance in human saliva has been reported, however the distribution of these proteins in other mammals is still unclear. Here, we performed a proteomic analysis of the saliva of several mammals and studied the evolution of this multigene family. The proteomic analysis detected S-type cystatins (S, SA, and SN) in human saliva and cystatin D in rat saliva. The evolutionary analysis showed that the cystatin C encoding gene is present in species of the most representative mammalian groups, i.e. Artiodactyla, Rodentia, Lagomorpha, Carnivora and Primates. On the other hand, D and S-type cystatins are mainly retrieved from Primates, and especially the evolution of S-type cystatins seems to be a dynamic process as seen in Pongo abelii genome where several copies of CST1-like gene (cystatin SN) were found. In Rodents, a group of cystatins previously identified as D and S has also evolved. Despite the high divergence of the amino acid sequence, their position in the phylogenetic tree and their genome organization suggests a common origin with those of the Primates. These results suggest that the D and S type cystatins have emerged before the mammalian radiation and were retained only in Primates and Rodents. Although the mechanisms driving the evolution of cystatins are unknown, it seems to be a dynamic process with several gene duplications evolving according to the birth-and-death model of evolution. The factors that led to the appearance of a group of saliva-specific cystatins in Primates and its rapid evolution remain undetermined, but may be associated with an adaptive advantage.
authors.affiliation: QOPNA, Centro de Espectrometria de Massa, Departamento de Química, Universidade de Aveiro, Aveiro, Portugal; CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBio, Laboratório Associado, Universidade do Porto, Vairão, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: de Sousa-Pereira
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBio, Laboratório Associado, Universidade do Porto, Vairão, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Abrantes
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBio, Laboratório Associado, Universidade do Porto, Vairão, Portugal; Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal; SaBio - IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Pinheiro
authors.affiliation: Departamento de Ciências Veterinárias, CECAV, Universidade de Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Colaço
authors.affiliation: QOPNA, Centro de Espectrometria de Massa, Departamento de Química, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Vitorino
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBio, Laboratório Associado, Universidade do Porto, Vairão, Portugal; Centro de Investigação em Tecnologias da Saúde, IPSN, CESPU, Gandra, Portugal.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Esteves
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D015891:Cystatins / Q000737:chemistry / Q000235:genetics*; D004285:Dogs; D019143:Evolution, Molecular; D020440:Gene Duplication; D006736:Horses; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011323:Primates; D012377:Rodentia; D012756:Sheep
chemical_list: D015891:Cystatins