Abstract
In humans, the single polymorphic B locus of the major histocompatibility complex is linked to the microsatellite MIB. In rhesus macaques, however, haplotypes are characterized by the presence of unique combinations of multiple B genes, which may display different levels of polymorphism. The aim of the study was to shed light on the evolutionary history of this highly complex region. First, the robustness of the microsatellite MIB-linked to almost half of the B genes in rhesus macaques (Mamu-B)–for accurate B haplotyping was studied. Based on the physical map of an established haplotype comprising 7 MIB loci, each located next to a certain Mamu-B gene, two MIB loci, MIB1 and MIB6, were investigated in a panel of MHC homozygous monkeys. MIB1 revealed a complex genotyping pattern, whereas MIB6 analysis resulted in the detection of one or no amplicon. Both patterns are specific for a given B haplotype, show Mendelian segregation, and even allow a more precise haplotype definition than do traditional typing methods. Second, a search was performed for retroelements that may have played a role in duplication processes as observed in the macaque B region. This resulted in the description of two types of duplicons. One basic unit comprises an expressed Mamu-B gene, adjacent to an HERV16 copy closely linked to MIB. The second type of duplicon comprises a Mamu-B (pseudo)gene, linked to a truncated HERV16 structure lacking its MIB segment. Such truncation seems to coincide with the loss of B gene transcription. Subsequent to the duplication processes, recombination between MIB and Mamu-B loci appears to have occurred, resulting in a hyperplastic B region. Thus, analysis of MIB in addition to B loci allows deciphering of the compound evolutionary history of the class I B region in Old World monkeys.
Highlights
Gene products of the Major Histocompatibility Complex (MHC), a multicopy gene system present in most vertebrate species, play a key role in immune-related defense reactions
Equivalents of the nonclassical HLA class I genes HLA-E and -F that are characterized by a low degree of polymorphism and differential tissue distribution, have be detected in the rhesus macaque and have been named Mamu-E and -F [18,19]
Animals The Biomedical Primate Research Centre houses a selfsustaining outbred colony of about 650 rhesus macaques that have been pedigreed based on the segregation of serologically defined MHC haplotypes
Summary
Gene products of the Major Histocompatibility Complex (MHC), a multicopy gene system present in most vertebrate species, play a key role in immune-related defense reactions. Equivalents of the nonclassical HLA class I genes HLA-E and -F that are characterized by a low degree of polymorphism and differential tissue distribution, have be detected in the rhesus macaque and have been named Mamu-E and -F [18,19]. Analysis of a large panel of rhesus macaques of Indian and Chinese origin showed that the copy number and content of B loci could vary significantly per chromosome [22,23,24]. Some of these genes, for example Mamu-I ( named B3), may represent nonclassicals with specialized functions [25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
