BETA-D-GLUCOSYL-HYDROXYMETHYLURACIL IS A CONSERVED DNA MODIFICATION IN KINETOPLASTID PROTOZOANS AND IS ABUNDANT IN THEIR TELOMERES

The unusual DNA base beta-D-glucosyl-hydroxymethyluracil, called ''J,' ' replaces approximate to 0.5-1% of Thy in DNA of African trypanosomes but has not been found in other organisms thus far, In Trypanosoma br ucei, J is located predominantly in repetitive DNA, and its presence c orrelates with the silencing of telomeric genes, Using antibodies spec ific for J, we have developed sensitive assays to screen for J in a ra nge of organisms and have found that J is not limited to trypanosomes that undergo antigenic variation but is conserved among Kinetoplastida , In all kinetoplastids tested, including the human pathogens Leishman ia donovani and Trypanosoma cruzi, J was found to be abundantly presen t in the (GGGTTA)(n) telomere repeats. Outside Kinetoplastida, J was f ound only in Diplonema, a small phagotrophic marine flagellate, in whi ch we also identified 5-MeCyt. Fractionation of Diplonema DNA showed t hat the two modifications are present in a common genome compartment, which suggests that they may have a similar function. Dinoflagellates appear to contain small amounts of modified bases that may be analogs of J. The evolutionary conservation of J in kinetoplastid protozoans s uggests that it has a general function, repression of transcription or recombination, or a combination of both, T. brucei may have recruited J for the control of genes involved in antigenic variation.