Absence of CD59 in Guinea Pigs: Analysis of the Genome Suggests the Evolution of a Pseudogene.

CD59 is a membrane-bound regulatory protein that inhibits the assembly of the terminal membrane attack complex (C5b-9) of complement. From its original discovery in humans almost 30 years ago, CD59 has been characterized in a variety of species, from primates to early vertebrates, such as teleost fish. CD59 is ubiquitous in mammals; however, we have described circumstantial evidence suggesting that guinea pigs () lack CD59, at least on erythrocytes. In this study, we have used a combination of phylogenetic analyses with syntenic alignment of mammalian genes to identify the only span of genomic DNA in that is homologous to a portion of mammalian and show that this segment of DNA is not transcribed. We describe a pseudogene sharing homology to exons 2 through 5 of human present in the genome. This pseudogene was flanked by homologs of two genes, and , a relationship and orientation that were consistent with other known mammalian genes. Analysis using RNA sequencing confirmed that this segment of chromosomal DNA was not transcribed. We conclude that guinea pigs lack an intact gene encoding CD59; to our knowledge, this is the first report of a mammalian species that does not express a functional CD59. The pseudogene we describe is likely the product of a genomic deletion event during its evolutionary divergence from other members of the rodent order.