title: Pseudogenization of CCL14 in the Ochotonidae (pika) family.
abstract: The interaction between chemokines and their receptors is crucial for inflammatory cell trafficking. CCL14 binds with high affinity to CCR5. In leporids, CCR5 underwent gene conversion with CCR2. The study of CCR5 ligands in leporid species showed that CCL8 is pseudogenized, while CCL3, CCL4 and CCL5 are functional. Here, we study the evolution of CCL14 in mammals with emphasis in the order Lagomorpha. By employing maximum likelihood methods we detected six sites under positive selection. Some of these sites are located in regions crucial for CCL14 activation and binding to receptors. Sequencing of CCL14 in Ochotona species showed that O. princeps, O. pallasi, O. alpina and O. turuchanensis have a mutation at the start codon (Met > Thr), while O. hoffmanni, O. mantchurica, O. dauurica and O. rufescens present the mammalian conserved Met. Ochotona hyperborea has the two alleles. In O. pusilla, CCL14 is a pseudogene due to a seven base pair insertion. Like CCL3, CCL4 and CCL5, CCL14 is functional in all leporids but in the Ochotonidae family it underwent a pseudogenization process. This suggests that CCL14 has an important biological role in other mammals by evolving under positive selection that has been lost in Ochotonidae (subgenera Pika and Lagotona).
authors.affiliation: CIBIO, InBIO - Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, Vairão, Portugal UMIB - Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) - UPorto, Porto, Portugal.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Neves
authors.affiliation: CIBIO, InBIO - Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, Vairão, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Abrantes
authors.affiliation: Zoological Museum of Moscow State University, B. Nikitskaya, 6, Moscow 125009, Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Lissovsky
authors.affiliation: CIBIO, InBIO - Research Network in Biodiversity and Evolutionary Biology, Universidade do Porto, Campus de Vairão, Rua Padre Armando Quintas, Vairão, Portugal CITS - Centro de Investigação em Tecnologias de Saúde, CESPU, Gandra, Portugal pjesteves@cibio.up.pt.
authors.forename: Pedro José
authors.initials: PJ
authors.lastname: Esteves
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002465:Cell Movement / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics*; D005785:Gene Conversion; D007793:Lagomorpha; D016013:Likelihood Functions; D008322:Mammals; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011544:Pseudogenes / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D019742:Chemokines, CC; D054390:Receptors, CCR2; D019713:Receptors, CCR5
keywords: CCL14; Chemokine ligands; Ochotonidae; evolution; pseudogenization