Extensive diversification of IgH subclass-encoding genes and IgM subclass switching in crocodilians

Crocodilians are a group of reptiles that are closely related to birds and are thought to possess a strong immune system. Here we report that the IgH locus in the Siamese crocodile and the Chinese alligator contains multiple μ genes, in contrast to other tetrapods. Both the μ2 and μ3 genes are expressed through class-switch recombination involving the switch region and germline transcription. Both IgM1 and IgM2 are present in the serum as polymers, which implies that IgM class switching may have significant roles in humoural immunity. The crocodilian α genes are the first IgA-encoding genes identified in reptiles, and these genes show an inverted transcriptional orientation similar to that of birds. The identification of both α and δ genes in crocodilians suggests that the IgH loci of modern living mammals, reptiles and birds share a common ancestral organization. Different mechanisms for generating antibody diversity have evolved since the emergence of immunoglobulin genes in jawed vertebrates. By sequencing the crocodilian immunoglobulin heavy-chain locus, Cheng et al . uncover new insights into the evolutionary origins of adaptive immunity.