Box 2 (doc 38K)

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Box 2: Hypotheses to explain the occurrence of dimorphic allele lineages in Plasmodium
falciparum (in chronological order)
Local adaptation (Tanabe et al., 1987):
“Suppose the two alleles produce proteins with equivalent function in the parasite but
different mechanisms of action. For example, both could participate in red cell
recognition or invasion but bind different groups on the red cell surface. This would
account for localized diversity in their structure (the recognition domains) and allow
for constant regions (the structural domains controlling processing and membrane
association). Such proteins could have evolved separately in biologically isolated
populations of the parasite, perhaps when P. falciparum was becoming infectious to
man. During subsequent evolution, when the populations fused and interbred, functional
constraints would perpetuate the dimorphism of the two alleles, but allow some
intragenic recombination.”
Gene duplication and recent population admixture (Miller et al, 1993):
“One might imagine a gene duplication event that allowed one gene to drift in the
absence of selective pressure and then the loss of one or the other gene in each of
the dominant ancestral lines. We find it simpler to think that the dimorphism itself
arose from two geographically isolated sources of P. falciparum and that as man became
peripatetic and malaria spread, the geographic barriers that allowed dimorphic forms
to evolve dissolved.”
Proliferation and deletion of repeat motifs (Rich and Ayala, 2000):
“The distinctive dimorphism of the two P. falciparum alleles results from
proliferation of repeats in two different regions of the molecule [MSP-2]. Presumably
because the overall MSP-2 molecule is constrained in size, the proliferation of
repeats leads consequently to loss of nucleotides along the gene regions; i.e., the
3D7 repeat precursors were lost in FC27 alleles, and the FC27 repeat precursors were
lost in 3D7 alleles.”
Gene duplication (Hartl et al., 2002):
“Variation as extreme, and apparently as ancient, as found in the Msp-1 alleles could
arise by gene duplication and divergence. Especially if the MAD20-like and K1-like
antigens are mutually antagonistic, chromosomes with paralogous copies of MAD20-like
and K1-type alleles would be strongly favoured under conditions of low transmission.
Under conditions of high transmission with many multiple infections, the selection
would be less intense and, through either deletion or unequal crossing-over, the
different lineages could lose one or the other paralog. This would create a situation
in which the Msp-1 alleles in the contemporary population are highly divergent and
extremely ancient, even though they derived from a single haploid genome when they
were still paralogs.”
Introgression (Polley et al., 2005):
“An introgression event could reconcile conflicting evidence from the genome for the
age of P. falciparum alleles (...). Fertilisation between two different species of
malaria parasite during the sexual stage of the malaria life cycle could rapidly
introduce novel polymorphisms into many loci. Although many of these would
subsequently be lost due to the effects of purifying selection and random genetic
drift, a recent introgression event might still leave some polymorphisms intact
through purely neutral processes.”
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