The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes

Gjini, E., Haydon, D.T. , Barry, J.D. and Cobbold, C.A. (2012) The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes. Molecular Biology and Evolution, 29(11), pp. 3321-3331. (doi: 10.1093/molbev/mss166)

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Abstract

Patterns of genetic diversity in parasite antigen gene families hold important information about their potential to generate antigenic variation within and between hosts. The evolution of such gene families is typically driven by gene duplication, followed by point mutation and gene conversion. There is great interest in estimating the rates of these processes from molecular sequences for understanding the evolution of the pathogen and its significance for infection processes. In this study, a series of models are constructed to investigate hypotheses about the nucleotide diversity patterns between closely related gene sequences from the antigen gene archive of the African trypanosome, the protozoan parasite causative of human sleeping sickness in Equatorial Africa. We use a hidden Markov model approach to identify two scales of diversification: clustering of sequence mismatches, a putative indicator of gene conversion events with other lower-identity donor genes in the archive, and at a sparser scale, isolated mismatches, likely arising from independent point mutations. In addition to quantifying the respective probabilities of occurrence of these two processes, our approach yields estimates for the gene conversion tract length distribution and the average diversity contributed locally by conversion events. Model fitting is conducted using a Bayesian framework. We find that diversifying gene conversion events with lower-identity partners occur at least five times less frequently than point mutations on variant surface glycoprotein (VSG) pairs, and the average imported conversion tract is between 14 and 25 nucleotides long. However, because of the high diversity introduced by gene conversion, the two processes have almost equal impact on the per-nucleotide rate of sequence diversification between VSG subfamily members. We are able to disentangle the most likely locations of point mutations and conversions on each aligned gene pair.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cobbold, Professor Christina and Haydon, Professor Daniel and Gjini, Ms Erida
Authors: Gjini, E., Haydon, D.T., Barry, J.D., and Cobbold, C.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Science and Engineering > School of Mathematics and Statistics > Mathematics
Journal Name:Molecular Biology and Evolution
Publisher:Oxford University Press
ISSN:0737-4038
ISSN (Online):1537-1719
Published Online:25 June 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in Molecular Biology and Evolution 29(11):3321-3331
Publisher Policy:Reproduced under a Creative Commons License

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