Phenotypic variation, molecular

Moran, A.P., Knirel, Y.A., Senchenkova, S.N., Widmalm, G., Hynes, S.O., Jansson, P.-E. Phenotypic variation in molecular mimicry between Helicobacter pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. Acid-induced phase variation in Lewis 1 and Lewisy expression by H. pylori lipopolysaccharides. J Biol Chem 277 (2002a) 5785-5795. 

In parallel, extensive studies on P. falciparum field isolates in Gabon [140-142], Senegal [143], Cambodia [118, 119, 144], and the Thailand Burmese border [145] corroborated the efficacy of FQ on the parasite whatever its resistance level to chloroquine or to other commonly used antimalarials mefloquine, quinine, halofantrine, and artemisinin derivatives [146, 147]. The cross reactivity observed in some studies with CQ was limited and it was demonstrated that it was caused by differences in initial parasitemia among isolates at the start of the assays [141]. Independance of susceptibility of P. falciparum with phenotypic variation of pfcrt gene, responsible for CQ resistance, could be suspected from these results, but this was demonstrated at the molecular level on Cambodia isolates [148] and extended further on other genes currently involved in resistance to aminoquinoline antimalarials [89, 90]. 

Miyashita, N. and C.H. Langley 1988 Molecular and phenotypic variation of the white locus region in Drosophila melanogaster. Genetics 120 199-212. 

Other contributions to this book have taken a molecular view of parasitic nematodes, yet molecules make only a rather brief appearance here. This chapter has tried to show that parasitic nematodes are fascinatingly and tantalizingly diverse at a phenotypic level. It has focused particularly on diversity in phenotypes that are apparent in response to environmental conditions within or outside a host. The interaction of parasites with within-host factors is a major current research effort. However, helminth immunology is particularly notable for its inattention to diversity, especially when compared with the immunology of parasitic protozoa (Read and Viney, 1996). Observations of the interaction of host immunity with subsequent development in S. ratti show the potential power of such interactions. It is also clear that a principal mechanism of the action of host immune responses is against nematode fecundity (Stear et al., 1997). This is likely to be a molecularly complex interaction. Understanding this interaction, as well as variation in the interaction is interesting, but could also form the basis of control by transmission-reduction rather than eradication per se. 

Investigating phenotypic diversity is not easy. A basic requirement is to have different lines of parasite available and in natural host species. However, being aware of the possibility of variation between individual worms would be a start. The few studies that have molecularly considered individual worms (Bianco et al., 1990 Fraser and Kennedy, 1990 Currie et al., 1998) have found variation between individual worms. Such variation may be the basis of some experimental noise . Perhaps efforts should be focused on this noise The phenotypic diversity that exists in natural, and even laboratory, populations of nematodes is maintained there by natural selection. This tells us, anthropomorphically, that such diversity matters to parasitic nematodes. It is hoped that this chapter has shown that it should also matter to us. 

Another reason for the variation in 5-FU-related toxicity may be the detection of mutations in the DPYD gene. Most patients with 5-FU-related toxicity have multiple mutations in the DPYD gene. Flowever, only a few patients with a low DPD phenotype have a molecular basis for reduced activity. Although novel DPYD variants have been identified in studies, the DPYD mutations now described do not entirely explain polymorphic DPD activity and toxic response to 5-FU. 

---