RT Journal Article T1 Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis. A1 Delaye, Luis A1 Ruiz-Ruiz, Susana A1 Calderon, Enrique A1 Tarazona, Sonia A1 Conesa, Ana A1 Moya, Andres K1 stenoxenism K1 majors surface glycoproteins K1 glycosylphosphatidylinositol K1 natural selection AB Pneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigens, most sites under diversifying selection in Msg code for residues with large relative surface accessibility areas. We also found evidence of positive selection in part of the cell machinery used to export Msg to the cell surface. Specifically, we found that genes participating in glycosylphosphatidylinositol (GPI) biosynthesis show an increased rate of nonsynonymous substitutions (dN) versus synonymous substitutions (dS). GPI is a molecule synthesized in the endoplasmic reticulum that is used to anchor proteins to membranes. We interpret the aforementioned findings as evidence of selective pressure exerted by the host immune system on Pneumocystis species, shaping the evolution of Msg and several proteins involved in GPI biosynthesis. We suggest that genome evolution in Pneumocystis is well described by the Red-Queen hypothesis whereby genes relevant for biotic interactions show accelerated rates of evolution. PB Oxford University Press YR 2018 FD 2018 LK http://hdl.handle.net/10668/12581 UL http://hdl.handle.net/10668/12581 LA en NO Delaye L, Ruiz-Ruiz S, Calderon E, Tarazona S, Conesa A, Moya A. Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis. Genome Biol Evol. 2018 Jun 1;10(6):1596-1606. NO L.D. wishes to thank Eugenia Flores and Ana Fayos for support provided. This project has received funding from the Marie Curie International Research Staff Exchange Scheme within the 7th European Community Framework Program under grant agreement No 612583-DEANN. Part of this work was done during an internship of L.D. as invited professor at the Universidad de Valencia. Support from CONACYT (grant 454938) is gratefully acknowledged. This work was supported by grants to A.M. from the Spanish Ministry of Science and Competitivity (projects SAF 2012-31187, SAF2013-49788-EXP, SAF2015-65878-R), Carlos III Institute of Health (projects PIE14/00045, AC 15/00022 and AC15/00042), Generalitat Valenciana (project PrometeoII/2014/065) and cofinanced by FEDER DS RISalud RD Aug 5, 2025