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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-2-14
pubmed:abstractText
Plasmodium knowlesi parasites isolated from a rhesus monkey vaccinated with a 143,000/140,000 Mr merozoite surface protein no longer expressed this protein. To study the molecular basis for the mutations, a lambda gt11 cDNA expression library constructed from the original parasite clone was screened with rabbit antiserum specific for the 143,000/140,000 Mr protein. Two cDNA clones that mapped to the 5' and 3' ends of the gene hybridized to two chromosomes of 3.6 x 10(6) kilobases and 1.8 x 10(6) kilobases. The gene on the 3.6 x 10(6) base chromosome was identified as the gene expressing the 143,000/140,000 Mr protein. Since the two cDNA clones also hybridized at high stringency with the 1.8 x 10(6) base chromosome, it appears that the 143,000/140,000 Mr gene was involved in an ancestral duplication and interchromosomal transposition. We have analyzed mutant parasites, using the cDNA clones and a 7000 base fragment of genomic DNA that contains the 143,000/140,000 Mr gene. In one type of mutation, the 143,000/140,000 Mr protein was replaced by a 76,000/72,000 Mr protein. The identical restriction sites and the identical size of the mRNA indicated that a point mutation resulted in premature interruption of translation. Sequence analysis revealed an AT substitution for a C in the middle of the coding region of the gene that created a frameshift and a stop codon. In a second type of mutation, no protein was expressed; a 4000 base deletion encompassed the transcriptional unit of the gene. The rapid mutation under vaccine pressure of an otherwise stable parasite protein emphasizes the need to identify vaccine candidates in which mutations would be lethal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
203
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
707-14
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Molecular basis for mutation in a surface protein expressed by malaria parasites.
pubmed:affiliation
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
pubmed:publicationType
Journal Article