Songbirds Conserved Sites and Intron Size of MHC Class I Molecules Reveal a Unique Evolution in Vertebrates

A. Arnaiz-Villena*, V. Ruiz-del-Valle, P. Reche, P. Gomez-Prieto, E. Lowry, J. Zamora, C. Areces, D. Rey, C. Parga, J.I. Serrano-Vela
Department of Immunology, University Complutense, the Madrid Regional Blood Center, Madrid, Spain

© 2010 Arnaiz-Villena et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to the Departamento de Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Avenida Complutense s/n, 28040 Madrid, Spain; Tel: +34 913017354; Fax: +34 913017356; E-mails:


Birds are considered dinosaurs that passed the 65 million years ago bottleneck. Songbirds (Passeriformes) include about half extant bird species (about 5000) and are generally the most air-thriving bird species, concordantly with their small size. Mayor Histocompatibility complex (MHC) molecules stimulate immune responses against microbes and its class I molecules have seven conserved residues in all vertebrates from jawed-fishes, 300 million years ago, to humans, including chickens.

All wild songbird species tested by us (n=18) and others (n= 2) differ in α1 domain residue 10 and α2 residue 96 from all other vertebrates. Amplification, cloning and sequencing were performed by standard methods. Sequences alignment were done by using PAUP and MEGA programs software. Crystallographic studies were performed by using mammal and bird MHC molecules from MPID database and other sources and showed that these changes did not significantly vary the MHC class I molecule stability in songbirds.

Further α1 and α2 domain comparisons by simple Composition Distances and Bayesian Inference showed that songbirds overall MHC class I molecules are phylogenetically more separated from mammal than other birds molecules. In addition MHC class I introns from Passeriformes (songbirds) were found to be longer than humans, chicken introns being the shortest ones.

These small mainly air-borne dinosaurs (Passeriformes) have undergone a different evolutive pathway, regarding to MHC, than all other tested vertebrates and more terrestrial birds. This may have been originated by an altogether different dinosaurs linage origin or to adaptation to more aerial than terrestrial environment or other unknown cause. In any case, the specific changes observed in this work for class I molecules in songbirds have reached a entropic, stable solution similar to that reached by other vertebrates.

Keywords: Songbirds, MHC evolution, immunology, passerines, carduelis, serinus.