期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：26
页码：8036-8040
DOI：10.1073/pnas.1501844112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceEverybody loves dolphins. And orcas. And Mx (Myxovirus) genes. Mx genes are important immune genes that help mammals fight many RNA and DNA viruses, including HIV, measles, and flu. We make a surprising discovery: dolphins, orcas, and likely all toothed whales lost both Mx genes soon after they diverged from baleen whales and ungulates, which preserve these important genes intact. Because both genes were likely lost simultaneously, we speculate that a viral outbreak exploiting the Mx genes may have forced the toothed whale's ancestor to sacrifice both. Because the Mx genes are so important, and because all 56 nontoothed whale sequenced mammals carry Mx genes, our discovery makes an important contribution to help preserve these magnificent mammals. 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.
关键词：gene loss ; Mx genes ; cetaceans ; immune system ; toothed whales
