THE RIBOSOMAL DNA LOCI IN PLASMODIUM-FALCIPARUM ACCUMULATE MUTATIONS INDEPENDENTLY

Homogeneity of rDNA sequence within a cell is maintained by mechanisms working at the DNA level. The imperative to maintain homogeneity is t hought to result from pressure to maintain the sequence of the rRNA tr anscript. We have investigated the extent of sequence variation within and between members of a species that is unable to utilize some stand ard mechanisms of rDNA sequence correction. We have compared the seque nce of the internal transcribed spacer (ITS1) located between the 18 S rRNA and 5.8 S rRNA genes of five different loci of a single Plasmodi um falciparum genotype. The ITS1 sequences are identical at 80 to 91% of the positions among the three asexually expressed genes (A-types) a nd 75% between the two genes expressed during sporogony (S-types), wit h only 42 to 57% identity between the types. This is rather startling in that the differences described here for a single genome are greater than those normally seen when comparing rDNA units from distantly rel ated organisms. We observe an apparent conservation of secondary struc ture within ITS1 sequences from the different transcription units, whi ch would reflect a level of selection at the rRNA but the organism see ms to be quite tolerant of primary sequence variation. Investigation o f the mature coding region within the 18 S rRNA genes did not reveal s equence variation within A- and S-types from a single genotype. Howeve r, comparison of the 18 S rRNA coding region from 17 geographically di stinct strains reveals up to 10% sequence variation within a 400 nucle otide region. Hence homogeneity of rRNA units within a species does no t seem to be an imperative driven totally by selection at the RNA leve l. The extraordinary maintenance of homogeneity within rDNA units norm ally seen within a species appears to have significance beyond those t hat can be ascribed to the events involved in processing, assembly and function of the ribosome. (C) 1995 Academic Press Limited