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Different modes of Mhc evolution in primates
J Klein1, C O'hUigin, F Figueroa
1Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Federal Republic of Germany.
Abstract:
The human major histocompatibility complex (Mhc) is a chromosomal segment approximately 4 million bp long that contains > or = 84 genes. Some of these genes code for the class I and class II molecules, while the remaining genes code for complement components, cytochrome P450, tumor necrosis factor, and many other, unrelated proteins. We demonstrate on three examples (DP, C4-CYP21, and DRB) that different regions of the Mhc have different evolutionary histories. The organization of the DP region, which in humans contains four genes, was established in the ancestral Anthropoidea or earlier and has not changed since. The duplication that generated the two C4-CYP21 modules occurred in the ancestral Catarrhini or earlier, but the region has been undergoing periodic homogenizations via unequal crossing-over, which make paralogous genes in the same species more similar to each other than to orthologous genes of different species. The eight or nine genes of the DRB region were also generated in the ancestral Catarrhini, but the region has since been subject to frequent rearrangements, which generated various DRB haplotypes. Not only the alleles but, in part, also the haplotype polymorphism is evolving transspecifically. The DRB region of the Platyrrhini has an origin different from that of the Catarrhini. The picture emerging from these studies is that of both stability in some regions of the Mhc and tremendous evolutionary instability in other regions.
Insights
The human major histocompatibility complex (Mhc) shows varied evolutionary paths across its regions. Some Mhc regions are stable, while others, like the DRB region, exhibit significant evolutionary instability and rearrangements.
Area of Science:
- Genomics
- Evolutionary Biology
- Human Genetics
Background:
- The human major histocompatibility complex (Mhc) is a large genomic region containing over 84 genes.
- These genes encode critical molecules like class I and II, complement components, and various proteins.
Purpose of the Study:
- To investigate the distinct evolutionary histories of different regions within the human Mhc.
- To understand the mechanisms driving genetic diversity and stability in the Mhc.
Main Methods:
- Comparative genomic analysis of specific Mhc regions (DP, C4-CYP21, DRB) across different primate lineages.
- Examination of gene duplication, homogenization via unequal crossing-over, and rearrangements.
Main Results:
- The DP region shows ancient stability since the Anthropoidea ancestor.
- The C4-CYP21 region underwent duplication and periodic homogenization, leading to gene similarity within species.
- The DRB region, originating in Catarrhini ancestors, exhibits frequent rearrangements and transspecific haplotype evolution, with distinct Platyrrhini origins.
Conclusions:
- The Mhc is a mosaic of evolutionary stability and instability.
- Different Mhc regions possess unique evolutionary trajectories shaped by duplication, homogenization, and rearrangement events.