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Background  Within  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.    Methods  To 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.    Results  Mapping 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  msp 1 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 msp 1 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.    Conclusions  Allelic 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  msp 1 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 material  The online version of this article (10.1186/s12936-018-2475-2) contains supplementary material, which is available to authorized users.

malaria journal

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