Is DQB2 Functional Among Nonhuman Primates?

Abstract

The non-human primate class II genes are highly homologous to human class II genes. Within the HLA-DQ region, the human genome contains an apparent gene duplication, in which the expressed DQA1 and DQB1 genes are found approximately 40 kb telomeric of the DQA2 and DQB2 genes. In spite of apparently normal gene organization and RNA splice sites, the DQA2 and DQB2 genes (also known as “DX”), are usually referred to as “pseudogenes”, since their transcription has not been reported. This DQ-DX gene duplication has previously been thought to be a fairly recent evolutionary event, because DQB2 was not found in Old World monkeys (Gyllensten et al. 1990). However, using the polymerase chain reaction, the second exon of the DQB2 locus from four primate species i.e., a chimpanzee, (Pan troglodytes), a gorilla (Gorilla gorilla), a gibbon (Hylabates lar), and an owl monkey (Aotus trivirgatus) were amplified. Our observation that the DQB2 is present in an owl monkey suggests that this diversification could have occurred prior to diversification of owl monkey and Old World monkey lineages. Sequence analysis of the DQB2 amplified genes revealed an extremely high degree of conservation through primate evolution. The nucleotide patterns observed have several features with possible functional implications: [1] To date four distinct chimpanzee DQB2 alleles have been identified reminiscent of patterns of polymorphism found in human DQB1 alleles; [2] the ratio of productive to silent substitutions, particularly in the owl monkey and the chimpanzee, resembles that of a functional locus, and overall is 1:1.35 among the five species examined; and [3] the owl monkey DQB2 gene may be actively transcribed, since a DQB2 sequence was recovered using an RNA-PCR technique.