Abstract:
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 laboratoryadapted 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.