Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus

doi:10.1073/pnas.252348999

Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus

^†Laboratory of Biology and ^††Department of Mathematics, Osaka Institute of Technology, Osaka 535-8585, Japan;^‡ Department of Protozoology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan;^§ Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand Asia; ^¶Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900, Sao Paulo (SP), Brazil South America; ^∥Department of Parasitology and Institute of Malariology, Inje University College of Medicine, Pusan 614-735, South Korea Asia; and^** Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University School of Medicine, Tokyo 162-866, Japan

Edited by Louis H. Miller, National Institutes of Health, Rockville, MD, and approved October 11, 2002 (received for review June 11, 2002)

Abstract

The organization and allelic recombination of the merozoite surface protein-1 gene of Plasmodium vivax (PvMsp-1), the most widely prevalent human malaria parasite, were evaluated in complete nucleotide sequences of 40 isolates from various geographic areas. Alignment of 31 distinct alleles revealed the mosaic organization of PvMsp-1, consisting of seven interallele conserved blocks flanked by six variable blocks. The variable blocks showed extensive variation in repeats and nonrepeat unique sequences. Numerous recombination sites were distributed throughout PvMsp-1, in both conserved blocks and variable block unique sequences, and the distribution was not uniform. Heterozygosity of PvMsp-1 alleles was higher in Asia (0.953 ± 0.009) than in Brazil (0.813 ± 0.047). No identical alleles were shared between Asia and Brazil, whereas all but one variable block nonrepeat sequence found in Brazil occurred in Asia. These observations suggest that P. vivax populations in Asia are ancestral to Brazilian populations, and that PvMsp-1 has heterogeneity in frequency of allelic recombination events. Recurrent origins of new PvMsp-1 alleles by repeated recombination events were supported by a rapid decline in linkage disequilibrium between pairs of synonymous sites with increasing nucleotide distance, with little linkage disequilibrium at a distance of over 3 kb in a P. vivax population from Thailand, evidence for an effectively high recombination rate of the parasite. Meanwhile, highly reduced nucleotide diversity was noted in a region encoding the 19-kDa C-terminal epidermal growth factor-like domain of merozoite surface protein-1, a vaccine candidate.

Footnotes

↵ ‡‡ To whom correspondence should be addressed. E-mail: kztanabe{at}ge.oit.ac.jp.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this study have been deposited in the GenBank database (accession nos. –, –, –, , –, and –).
Abbreviations:
1. Rm, the minimum number of recombination events
2. MSP-1, merozoite surface protein-1
3. Pv, Plasmodium vivax
4. Pf, Plasmodium falciparum
5. h, heterozygosity