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In contrast, we could observe multiple changes in the transcriptome in late generation trt-1 mutants and the DM survivor strain, with 834 genes differentially expressed in the late generation trt-1 mutant strain and 2370 genes differentially expressed in the survivor strain (Supplementary Table 1).
The late generation trt-1 mutant and the survivor strain clustered closely together, whereas the early generation trt-1 mutant strains, the ceob2 mutant strain and the wt control animals clustered only randomly.
CD36 binding was one third of the original level in 3D7AH1S2 after 100 generations of growth and was not seen in the late generation parasites (Table 1 and data not shown).
Still, var2csa expression was dominant in the late generation parasites, which may in part be due to differences in proliferation rates in-between the var2csa- and non-var2csa expressing clones (Figure 7).
In fact, it has been reported that wild-type mice derived from the late generation of mTR+/− heterozygous parents which had short telomeres display hematopoietic phenotypes resembling aplastic anemia and dyskeratosis congenita [50].
Further, we do not know whether the var2csa locus in the late generation parasites (3D7S8.4.2-17 sub-clones) would remain activated until an episode of exogenous challenge or whether they spontaneously would switch at a slow rate to another var variant.
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