title: Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales.
abstract: Viral outbreaks in dolphins and other Delphinoidea family members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) and Mx2 defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances infectivity by multiple RNA and DNA viruses, including orthomyxoviruses (influenza A), paramyxoviruses (measles), and hepadnaviruses (hepatitis B), whereas loss of Mx2 function leads to decreased resistance to HIV-1 and other viruses. Here we show that both Mx1 and Mx2 have been rendered nonfunctional in Odontoceti cetaceans (toothed whales, including dolphins and orcas). We discovered multiple exon deletions, frameshift mutations, premature stop codons, and transcriptional evidence of decay in the coding sequence of both Mx1 and Mx2 in four species of Odontocetes. We trace the likely loss event for both proteins to soon after the divergence of Odontocetes and Mystocetes (baleen whales) ∼33-37 Mya. Our data raise intriguing questions as to what drove the loss of both Mx1 and Mx2 genes in the Odontoceti lineage, a double loss seen in none of 56 other mammalian genomes, and suggests a hitherto unappreciated fundamental genetic difference in the way these magnificent mammals respond to viral infections.
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA 94305;
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Braun
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305;
authors.forename: Amir
authors.initials: A
authors.lastname: Marcovitz
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305;
authors.forename: J Gray
authors.initials: JG
authors.lastname: Camp
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA 94305;
authors.forename: Robin
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA 94305; Department of Developmental Biology, Stanford University, Stanford, CA 94305; Department of Pediatrics, Stanford University, Stanford, CA 94305 bejerano@stanford.edu.
authors.forename: Gill
authors.initials: G
authors.lastname: Bejerano
mesh_terms: D000818:Animals; D006801:Humans; D064547:Myxovirus Resistance Proteins / Q000235:genetics*; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics*; D014907:Whales / Q000145:classification / Q000378:metabolism*
chemical_list: D064547:Myxovirus Resistance Proteins; D020033:Protein Isoforms
keywords: Mx genes; cetaceans; gene loss; immune system; toothed whales