MHC molecules are divided into class I and class II molecules that are located on the chromosome six .The class I MHC can be divided into two groups: classical class I or class Ia loci and nonclassical class I or class Ib loci. Class Ia includes three loci: A, B, and C and there are 25–50 class Ib, including pseudogenes. The class II gene can be divided into six major gene regions: DP, DN, DM, DO, DQ, and DR. Also, it consists of psudogenes and poorly expressed genes (6, 7).
Scientists believe class I and II have diverged about 500 million years ago. MHC molecules have a high level of polymorphism within loci. Although they have a high degree of polymorphism, intralocus variation is less than interlocus variation, but no or few interlocus genetic exchange happened. If interlocus genetic exchange had happened frequently, we would expect to have more similar genes between one species rather than the genes in another species, but this is not the case. For example, genes from loci A, B, and C are the same among humans and gorillas (Fig 3). Other observations show that some Ia genes became nonfunctional in different orders of mammals that made Nei and Hughes to conclude that MHC genes evolution happened with birth-and-death process of evolution. Distantly related organisms have distinctive sets of class Ia genes. This supports the theory that genes have differentiated by duplication, deletion or dysfunctioning (6, 7).
The class Ia loci from the Saguinus oedipus (New World monkey) are different from class Ia loci of humans, although there are some nonclassical loci that are orthologous. On the other hand, closely related species like humans, chimpanzees, and gorillas share the same loci A, B, and C genes. Some Ib genes have not been changed in the genome for a long time. For instance, the human MICA and HH genes have been intact in the human lineage for at least 300 million years. Nonclassical class I genes E, F, and G have survived longer than Ia genes A, B, and C. The nonclassical I genes (NC4, NC7, and NC8) in frog (Xenopus) have survived for a long time as well. This supports the theory that interlocus genetic exchange has not been frequent in class Ib genes too (6, 7).
Figure 5 is the tree for class II B genes in distantly related organisms. This tree supports that these genes have experienced birth-and-death evolution.