Gene copy number variation in natural populations of Plasmodium falciparum in Eastern Africa.
BACKGROUND
Gene copy number variants (CNVs), which consist of deletions and amplifications of single or sets of contiguous genes, contribute to the great diversity in the Plasmodium falciparum genome. In vitro studies in the laboratory have revealed their important role in parasite fitness phenotypes such as red cell invasion, transmissibility and cytoadherence. Studies of natural parasite populations indicate that CNVs are also common in the field and thus may facilitate adaptation of the parasite to its local environment.


RESULTS
In a survey of 183 fresh field isolates from three populations in Eastern Africa with different malaria transmission intensities, we identified 94 CNV loci using microarrays. All CNVs had low population frequencies (minor allele frequency < 5%) but each parasite isolate carried an average of 8 CNVs. Nine CNVs showed high levels of population differentiation (FST > 0.3) and nine exhibited significant clines in population frequency across a gradient in transmission intensity. The clearest example of this was a large deletion on chromosome 9 previously reported only in laboratory-adapted isolates. This deletion was present in 33% of isolates from a population with low and highly seasonal malaria transmission, and in < 9% of isolates from populations with higher transmission. Subsets of CNVs were strongly correlated in their population frequencies, implying co-selection.


CONCLUSIONS
These results support the hypothesis that CNVs are the target of selection in natural populations of P. falciparum. Their environment-specific patterns observed here imply an important role for them in conferring adaptability to the parasite thus enabling it to persist in its highly diverse ecological environment.
['Simam|Joan|J|', 'Rono|Martin|M|', 'Ngoi|Joyce|J|', 'Nyonda|Mary|M|', 'Mok|Sachel|S|', 'Marsh|Kevin|K|', 'Bozdech|Zbynek|Z|', 'Mackinnon|Margaret|M|']
D000222:Adaptation, Physiological D000351:Africa, Eastern D002648:Child D002675:Child, Preschool D002872:Chromosome Deletion D056915:DNA Copy Number Variations D005260:Female D006801:Humans D007223:Infant D008297:Male D010963:Plasmodium falciparum
Copy number variation Plasmodium falciparum Adaptation