Genomic evolution of MHC class I region in primates

Abstract

To elucidate the origins of the MHC-B-MHC-C pair and the MHC class I chain-related molecule (MIC)A-MICB pair, we sequenced an MHC class I genomic region of humans, chimpanzees, and rhesus monkeys and analyzed the regions from an evolutionary stand-point, focusing first on LINE sequences that are paralogous within each of the first two species and orthologous between them. Because all the long interspersed nuclear element (LINE) sequences were fragmented and nonfunctional, they were suitable for conducting phylogenetic study and, in particular, for estimating evolutionary time. Our study has revealed that MHC-B and MHC-C duplicated 22.3 million years (Myr) ago, and the ape MICA and MICB duplicated 14.1 Myr ago. We then estimated the divergence time of the rhesus monkey by using other orthologous LINE sequences in the class I regions of the three primate species. The result indicates that rhesus monkeys, and possibly the Old World monkeys in general, diverged from humans 27-30 Myr ago. Interestingly, rhesus monkeys were found to have not the pair of MHC-B and MHC-C but many repeated genes similar to MHC-B. These results support our inference that MHC-B and MHC-C duplicated after the divergence between apes and Old World monkeys.

Fig. 1.

Duplicated genomic fragments of MHC-B and MHC-C regions for humans and chimpanzees. Red, LINE fragmentary sequences used for the present analysis; blue, other sequences. Sequences on top of the line are located in 5′ to 3′ direction, whereas sequences underneath the line are in the 3′ to 5′ direction. Yellow square, an exon of the MHC gene. Other neighboring sequences are also presented to clarify that the LINEs used are paralogous within the species and orthologous between the species. Yellow area, insertion/deletion among the four fragmented sequences; gray area, a region outside of a duplicated fragment. Shown are MHC-B fragment of chimpanzees (a), MHC-B fragment of humans (b), MHC-C fragment of humans (c), and MHC-C fragment of chimpanzees (d).

Fig. 2.

Duplications of the MHC-B-MHC-C pair and the MICA-MICB pair in reference to phylogeny of humans, chimpanzees, and rhesus monkeys. The vertical axis indicates time in Myr in ascending order. We cited the divergence time between humans and chimpanzees (5.4 Myr ago) to calibrate the divergence between rhesus monkeys and humans or chimpanzees and the two events of duplication, as depicted in the figure.