Malaria infects over 200 million individuals and kills 2 million young chil
dren every year. Understanding the biology of malarial parasites will be fa
cilitated by DNA microarray technology, which can track global changes in g
ene expression under different physiological conditions. However, genomes o
f Plasmodium sp. (and many other important pathogenic organisms) remain to
be fully sequenced so, currently, it is not possible to construct gene-spec
ific microarrays representing complete malarial genomes. In this study, 364
8 random inserts from a Plasmodium falciparum mung bean nuclease genomic li
brary were used to construct a shotgun DNA microarray. Through differential
hybridization and sequencing of relevant clones, large differences in gene
expression were identified between the blood stage trophozoite form of the
malarial parasite and the sexual stage gametocyte form. The present study
lengthens our list of stage-specific transcripts in malaria by at least an
order of magnitude above all previous studies combined. The results offer a
n unprecedented number of leads for developing transmission blocking agents
and for developing vaccines directed at blood stage antigens. A significan
t fraction of the stage-selective transcripts had no sequence homologues in
the current genome data bases, thereby underscoring the importance of the
shotgun approach. The malarial shotgun microarray will be useful for unrave
lling additional important aspects of malaria biology and the general appro
ach may be applied to any organism, regardless of how much of its genome is
sequenced.