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Structure, sequence, and transcriptional analysis of the Babesia bovis rap-1 multigene locus
The complexity of multigene families encoding rhoptry proteins and the generation of new variants in these families are constraints to development of vaccines incorporating rhoptry proteins. For example, the Babesia bigemina rhoptry associated protein ( rap) -1 locus is composed of tandemly arranged...
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Published in: | Molecular and biochemical parasitology 1998-06, Vol.93 (2), p.215-224 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | The complexity of multigene families encoding rhoptry proteins and the generation of new variants in these families are constraints to development of vaccines incorporating rhoptry proteins. For example, the
Babesia bigemina rhoptry associated protein (
rap)
-1 locus is composed of tandemly arranged genes including four polymorphic
rap-1a genes and two classes of divergent genes,
rap-1b and
rap-1c.
B. bigemina rap-1 polymorphism reflects recombination and gene conversion and results in multiple RAP-1 proteins with unique B- and T-cell epitopes. Is this complex locus structure and recombination a required feature of the
rap-1 gene family among
Babesia species? We addressed this question by analysis of the
rap-1 locus in
B. bovis. Sequence analysis of an 11 kb genomic clone representing the
B. bovis rap-1 locus revealed only two identical and continuous
rap-1a gene copies,
rap1a-1 and
rap-1a-2, located in a similar head to tail orientation. Using the conserved
ig gene as a marker for the 3′ boundary of the
rap-1 locus, we conclude that divergent
rap-1b and
rap-1c genes, present in
B. bigemina, are not similarly
cis-linked to the
B. bovis
rap-1 locus. Analysis of the
rap-1a genes 1 and 2 from each of multiple
B. bovis strains from North and South America demonstrated RAP-1 size conservation with very limited amino acid sequence variation. The results suggest that the simple two gene arrangement in the
B. bovis rap-1 gene family was generated by gene duplication and, in contrast to the
B. bigemina rap-1 locus, both genes evolved together using homogenization mechanisms with point mutation as the single mechanism for gene variation. Three discontinuous non-
rap-1 genes are closely
cis-linked to the
B. bovis
rap-1 locus and the presence of multiple introns in these genes may limit
rap-1 gene variation due to unequal crossing over. The different mechanisms likely involved in the evolution of the
rap-1 family in
B. bigemina versus
B. bovis are reflected in the marked structural and antigenic polymorphism in the
B. bigemina RAP-1 molecules as compared with the essentially monomorphic RAP-1 in
B. bovis. |
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ISSN: | 0166-6851 1872-9428 |
DOI: | 10.1016/S0166-6851(98)00032-2 |