@article{fdi:010048369,
  title = {{P}opulation diversity and antibody selective pressure to {P}lasmodium falciparum {MSP}1 block2 locus in an {A}frican malaria-endemic setting},
  author = {{N}oranate, {N}. and {P}rugnolle, {F}ranck and {J}ouin, {H}. and {T}all, {A}. and {M}arrama, {L}. and {S}okhna, {C}heikh and {E}kala, {M}. {T}. and {G}uillotte, {M}. and {B}ischoff, {E}. and {B}ouchier, {C}. and {P}atarapotikul, {J}. and {O}hashi, {J}. and {T}rape, {J}ean-{F}ran{\c{c}}ois and {R}ogier, {C}. and {M}ercereau-{P}uijalon, {O}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {G}enetic evidence for diversifying selection identified the {M}erozoite {S}urface {P}rotein1 block2 ({P}f{MSP}1 block2) as a putative target of protective immunity against {P}lasmodium falciparum. {T}he locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. {T}he family-specific antibody responses observed in endemic settings support immune selection operating at the family level. {H}owever, the factors contributing to the large intra-family allelic diversity remain unclear. {T}o address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single {S}enegalese rural community where malaria transmission is intense and perennial. {R}esults: {F}amily distribution showed no significant temporal fluctuation over the 10 y period surveyed. {S}equencing of 358 {PCR} fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. {T}he parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. {P}opulation diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. {S}eroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. {R}eactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. {S}eroreactivity to {K}1-, {M}ad20- and {R}033 families correlated with the relative family genotype distribution within the village. {A}ntibody specificity remained unchanged with cumulated exposure to an increasingly large number of alleles. {C}onclusion: {T}he {P}fmsp1 block2 locus presents a very large population sequence diversity. {T}he lack of stable acquisition of novel antibody specificities despite exposure to novel allelic forms is reminiscent of clonal imprinting. {T}he locus appears under antibody-mediated diversifying selection in a variable environment that maintains a balance between the various family types without selecting for sequence variant allelic forms. {T}here is no evidence of positive selection for intrafamily sequence diversity, consistent with the observed characteristics of the antibody response.},
  keywords = {},
  booktitle = {},
  journal = {{B}mc {M}icrobiology},
  volume = {9},
  numero = {},
  pages = {219},
  ISSN = {1471-2180},
  year = {2009},
  DOI = {10.1186/1471-2180-9-219},
  URL = {https://www.documentation.ird.fr/hor/fdi:010048369},
}