COMPUTATIONAL PREDICTION OF MHC II-ANTIGEN BINDING SUPPORTS DIVERGENT ALLELE ADVANTAGE AND EXPLAINS TRANS-SPECIES POLYMORPHISM
Article first published online: 20 APR 2011
© 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.
Volume 65, Issue 8, pages 2380–2390, August 2011
How to Cite
Lenz, T. L. (2011), COMPUTATIONAL PREDICTION OF MHC II-ANTIGEN BINDING SUPPORTS DIVERGENT ALLELE ADVANTAGE AND EXPLAINS TRANS-SPECIES POLYMORPHISM. Evolution, 65: 2380–2390. doi: 10.1111/j.1558-5646.2011.01288.x
- Issue published online: 26 JUL 2011
- Article first published online: 20 APR 2011
- Accepted manuscript online: 11 MAR 2011 08:51AM EST
- Received November 15, 2011, Accepted February 24, 2011
- Allele divergence;
- balancing selection;
- major histocompatibility complex;
- peptide binding
The major histocompatibility complex (MHC), coding for antigen presenting molecules of the adaptive immune system, represents one of the most polymorphic regions in the vertebrate genome. The exceptional polymorphism, which is potentially maintained by balancing selection under host–parasite coevolution, comprises excessive sequence divergence among alleles as well as ancient allelic lineages that predate species divergence (trans-species polymorphism). Here, the mechanisms that are proposed to maintain such sequence divergence and ancient lineages are investigated. Established computational antigen-binding prediction algorithms, which are based on empirical databases, are employed to determine the overlap in bound antigens among individual MHC class IIB alleles. The results show that genetically more divergent allele pairs experience less overlap and thus present a broader range of potential antigens. These findings support the divergent allele advantage hypothesis and furthermore suggest an evolutionary advantage explaining the maintenance of divergent allelic lineages, that is, trans-species polymorphism. In addressing a quantitative rather than qualitative aspect of MHC alleles, these insights highlight a new direction for future research on MHC evolution.