Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc

Peri, Sateesh; Kulkarni, Asmita; Feyertag, Felix; Berninsone, Patricia M; Alvarez-Ponce, David

We found a putatively functional CMAH coding sequence in the dog genome, consistent with prior results from Ng et al. (2014) , who showed the presence of conserved CMAH coding exons 3, 5, 8, 11, and 12 in dogs. The dog genome assemblies available from the NCBI Genome database correspond to three breeds of European ancestry (boxer, poodle, and beagle). Dogs of Western ancestry seem to lack significant levels Neu5Gc, but Western dog breed cells exhibit low levels of canine CMAH transcripts and protein (Lö fling et al. 2013), consistent with our observations. Bats (order Chiroptera) are commonly classified into suborders Yangchiroptera and Yinchiroptera (Teeling et al. 2005; Tsagkogeorga et al. 2013; Lei and Dong 2016) . Although one study showed that the milk of island flying fox, Pteropus hypomelanus (Pteropodidae, Yinchiroptera) contains Neu5Gc (Senda et al. 2011) , no studies have reported the levels of Neu5Gc in other bat species. The NCBI Genome database contains the genomes of seven Yinchiroptera and six Yangchiroptera species. We found CMAH sequences in the families Pteropodidae and Megadermatidae of Yinchiroptera and in the family Mormoopidae of Yangchiroptera. In contrast, CMAH gene could not be detected in two species belonging to Rhinolophidae and Hipposideridae (Yinchiroptera) and in all five species belonging to Vespertillionidae (Yangchiroptera). Thus, the CMAH gene has undergone independent gene losses in both Yinchiroptera and Yangchiroptera ( fig. 4) .