Major histocompatibility complex (MHC) class I and class II molecules bind
to and display peptidic antigens acquired from pathogens that are recognize
d by lymphocytes coordinating and executing adaptive immune responses. The
two classes of MHC proteins have nearly identical tertiary structures and w
ere derived from a common ancestor that probably existed not long before th
e emergence of the cartilaginous fish. Class I and class II genes are genet
ically linked in tetrapods but are not syntenic in teleost fish, a phylogen
etic taxon derived from the oldest vertebrate ancestor examined to date. Ca
rtilaginous fish (sharks, skates, and rays) are in the oldest taxon of exta
nt jawed vertebrates; we have carried out segregation analyses in two famil
ies of nurse sharks and one family of the banded houndshark that revealed a
close linkage of class II alpha and beta genes both with each other and wi
th the classical class I (class Ia) gene. These results strongly suggest th
at the primordial duplication giving rise to classical class I and class II
occurred in cis, and the close linkage between these two classes of genes
has been maintained for at least 460 million years in representatives of mo
st vertebrate taxa.