Recent Progress in Functional Genomic Research in Plasmodium falciparum

Abstract

With the completion and near completion of many malaria parasite genome-sequencing projects, efforts are now being directed to a better understanding of gene functions and to the discovery of vaccine and drug targets. Inter- and intraspecies comparisons of the parasite genomes will provide invaluable insights into parasite evolution, virulence, drug resistance, and immune invasion. Genome-wide searches for loci under various selection pressures may lead to discovery of genes conferring drug resistance or encoding for protective antigens. In addition, the Plasmodium falciparum genome sequence provides the basis for the development of various microarrays to monitor gene expression and to detect nucleotide substitution and deletion/amplification. Genome-wide profiling of the parasite proteome, chromatin modification, and nucleosome position also depend on availability of the parasite genome. In this brief review, we will highlight some recent advances and studies in characterizing gene function and related phenotype in P. falciparum that were made possible by the genome sequence, particularly the development of a genome-wide diversity map and various high-throughput genotyping methods for genome-wide association studies (GWAS).

PfCRT and its role in antimalarial drug resistance

“…Field studies have repeatedly shown that K76T also provides a highly sensitive, albeit only moderately specific, marker for CQ treatment failure [31] (see below). A primary role for mutant PfCRT in driving CQR worldwide is consistent with population and genome-wide association studies that demonstrate the worldwide dissemination of mutant alleles from a handful of successful origins of resistance in a CQ-driven selective sweep [32, 33]. …”

Analysis of Antibodies to Newly Described Plasmodium falciparum Merozoite Antigens Supports MSPDBL2 as a Predicted Target of Naturally Acquired Immunity

“…Characterization of naturally acquired human antibody responses to specific antigens has been undertaken to describe associations with protection from clinical malaria, highlighting a need for simultaneous analysis of multiple antigens (3–5). Analysis of transcripts and proteins (6–9) and genomic (10, 11) and population genetic (12–16) studies of P. falciparum have identified new genes that may encode promising candidates for a vaccine.…”

Annotation transfer by homology among closely related genomes helps to identify protein function in Plasmodium species

“…So the annotation of the large number of remaining hypothetical proteins could be of immensely helpful in tackling the disease. Though the annotation transfer by homology has its limitations like requirement of significant similarity (Rost et al, 2003), new gene families were indeed discovered by this method (Mu et al, 2010). The annotation of these large numbers of proteins can be accomplished only with large concerted effort (Roberts, 2004).…”