An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data

Abstract

BackgroundWithin Plasmodium falciparum merozoite surface protein 1 (MSP1), the N-terminal block 2 region is a highly polymorphic target of naturally acquired antibody responses. The antigenic diversity is determined by complex repeat sequences as well as non-repeat sequences, grouping into three major allelic types that appear to be maintained within populations by natural selection. Within these major types, many distinct allelic sequences have been described in different studies, but the extent and significance of the diversity remains unresolved.MethodsTo survey the diversity more extensively, block 2 allelic sequences in the msp1 gene were characterized in 2400 P. falciparum infection isolates with whole genome short read sequence data available from the Pf3K project, and compared with the data from previous studies.ResultsMapping the short read sequence data in the 2400 isolates to a reference library of msp1 block 2 allelic sequences yielded 3815 allele scores at the level of major allelic family types, with 46% of isolates containing two or more of these major types. Overall frequencies were similar to those previously reported in other samples with different methods, the K1-like allelic type being most common in Africa, MAD20-like most common in Southeast Asia, and RO33-like being the third most abundant type in each continent. The rare MR type, formed by recombination between MAD20-like and RO33-like alleles, was only seen in Africa and very rarely in the Indian subcontinent but not in Southeast Asia. A combination of mapped short read assembly approaches enabled 1522 complete msp1 block 2 sequences to be determined, among which there were 363 different allele sequences, of which 246 have not been described previously. In these data, the K1-like msp1 block 2 alleles are most diverse and encode 225 distinct amino acid sequences, compared with 123 different MAD20-like, 9 RO33-like and 6 MR type sequences. Within each of the major types, the different allelic sequences show highly skewed geographical distributions, with most of the more common sequences being detected in either Africa or Asia, but not in both.ConclusionsAllelic sequences of this extremely polymorphic locus have been derived from whole genome short read sequence data by mapping to a reference library followed by assembly of mapped reads. The catalogue of sequence variation has been greatly expanded, so that there are now more than 500 different msp1 block 2 allelic sequences described. This provides an extensive reference for molecular epidemiological genotyping and sequencing studies, and potentially for design of a multi-allelic vaccine.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2475-2) contains supplementary material, which is available to authorized users.

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces

“…When magnified to understand the extent of parasite diversity in these provinces, the msp1 MAD20 allelic family (99%) and the msp2 3D7 allelic family was predominant (97%). These results are in accordance with an earlier study from Vietnam [ 17 ]. Another longitudinal study in the region, in Myanmar between 2004 and 2006 and 2013–2015 shows changes in the msp1 and msp2 allele distribution over time [ 19 ].…”

“…In Vietnam, the predominant msp1 and msp2 alleles in 2012 [ 17 ] are MAD20 [ 18 ] and 3D7 [ 19 ], respectively. This study aims to determine the distribution of the Plasmodium species and subsequently the different msp1 , msp2 genotypes and to estimate the MOI in clinical isolates from malaria endemic areas in Vietnam.…”

Molecular epidemiology of Plasmodium falciparum by multiplexed amplicon deep sequencing in Senegal

“…These results are consistent with a previous observation of high levels of polymorphism in both Pfmsp1 (8K1-like, 14MAD20-like, 6 RO33-like) and Pfmsp2 (41 IC3D7-like, 18 FC27-like) using an amplicon deep sequencing technique in Myanmar [ 44 ]. Similar results have been also reported by Aspeling-Jones et al who identified 225 different K1-like, 123 different MAD20-like and 9 distinct RO33-like in Africa and Asia [ 45 ]. Most of these alleles were detected in the South, hyper-endemic area, 33 and 53 distinct alleles were observed for Pfmsp1 (18 K1-like, 8 MAD20-like, and 7 RO33-like) and Pfmsp2 (35 IC3D7-like and 18 FC27-like), respectively.…”

Development of Nested PCR-Heteroduplex Mobility Assay for Determination of Genetic Diversity in the Block 2 Region of the Plasmodium falciparum Merozoite Surface Protein 1 Gene

“…The block 2 allele is mainly represented by three families, namely, K1, MAD20, and RO33 in the field isolates. These families' allelic sequences show a highly diverse and specific geographical distribution [18]. In addition, the pattern and fragment size polymorphism of the block 2 allele serve as molecular indicators, host immunity, and malaria transmission dynamics [19].…”