Trends in Parasitology
The hitchhiker's guide to malaria parasite genes
Section snippets
Malaria parasites – strains and genetics
As recently as 40 years ago, virtually nothing was known of the genetics of the malaria parasite, the nature of its genome or how novel genotypes were generated. In 1966, Garnham published his classical book about malaria parasites [1], which included accounts of the natural history and morphology of >100 species of Plasmodium. At that time, it was realized that different ‘strains’ (see Glossary) of certain species existed, but the genetic basis of their differences was unknown. In Plasmodium
Early genetic work
From early in the 20th century, it was recognized that human or animal hosts could be infected with a mixture of different species of parasite – for example, mixed infections in humans of P. falciparum and Plasmodium vivax. However, until the 1960s, little attention had been given to the notion that infections by a single parasite species in a human, animal or vector host might consist of mixtures of genetically distinct strains. In malaria, this changed with the ability to distinguish
Genome, chromosomes and recombination
The genomes of all species of Plasmodium so far examined contain 14 chromosomes. In P. falciparum, homologous chromosomes vary in size between clones, and their sizes range from 0.643 Mb (chromosome 1) to 3.290 Mb (chromosome 14) in clone 3D7 [7]. Sequencing of the genome has revealed that, as a general rule, ‘house-keeping’ genes occur in the central portions of each chromosome, whereas regions near each end are highly variable, containing genes encoding polymorphic antigens and surface-related
Identifying genes by experimental linkage analysis
The procedure used in classical linkage analysis to identify which genes determine a phenotype is to make a cross between two parent strains differing not only by the character under investigation (e.g. resistance to a drug) but also by a large number of polymorphic genetic markers whose chromosomal locations are known. The progeny are then examined for the inheritance of each marker. The markers of each parent are expected to assort randomly into the progeny but those markers of the resistant
Identifying genes by field surveys – signatures of selection
The appearance and spread of resistance to chloroquine and to pyrimethamine in P. falciparum in most malaria-endemic countries of the world have been well documented over the past 50 years. With the large number of polymorphic markers now available, a question which can now be addressed is whether resistance to each drug has arisen independently at different places in each region, and whether specific mutants have spread from one region to another.
Crossing and recombination during mosquito
Future perspectives
Genetic methodology, whether by the use of experimental manipulation in the laboratory or population genetic analysis in the field, has come of age with regard to the malaria parasite. From being regarded by many as a subject of theoretical interest only, the importance and practical applications of genetics in the field of drug resistance are now unquestioned. Classical genetic analysis was fundamental to the identification of the pfdhfr and pfcrt genes, and these findings led directly to
Acknowledgements
I extend my sincere thanks to Richard Carter, Sandie Cheesman and Richard Culleton for their advice and comments about the manuscript.
Glossary
- Amplified fragment length polymorphism:
- a method for detecting large numbers of polymorphisms in the DNA of different strains of an organism, in which restriction enzyme digestion of DNA is carried out, and a subset of DNA fragments selected for PCR amplification and visualization [32]. [32]
- Clone:
- a group of organisms derived from a single cell by asexual reproduction. Classically, a clone consists of genetically identical organisms. However, with the increasing knowledge of processes such as
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