by Aaron G. Filler, MD, PhD
Figure 6-3 – Modification of Mutability by Environmental Factors
The rapidly evolving HIV genome demonstrates environmental effects on rate of mutation.
A – The speed of reverse transcription from RNA to DNA is affected by the concentration of various elements in the medium.
B – The polymerase enzyme produces fragments of the genome with standardized breakpoints sorted out by length in electrophoretic gel. Some elements cause improved readthrough – longer segments of DNA so that certain bands disappear in some channels.
C – RNA has a 3D structure of hairpins and loops. Breakpoints correspond to geometric twists and turns of the RNA.
D – HIV genome shows high rates of transcript breakage at loops and bends.
A - From: Filler, A.G. and A. M. L. Lever (1996). Nucleic acid amplification using scandium and lanthanum ions. US Patent 5,554,498. and - Filler, A. G. and A. M. Lever (1997). Effects of cation substitutions on reverse transcriptase and on human immunodeficiency virus production. AIDS Research and Human Retroviruses 13(4): 291-9.
C - From: Alberts, B. (2002). Molecular Biology of the Cell. New York, Garland Science. Drawing reproduced by permission Garland Science, Taylor & Francis.
D - Redrawn, modified, after: Harrison, G. P., M. S. Mayo, E. Hunter, A.M.L. Lever. (1998). Pausing of reverse transcriptase on retroviral RNA templates is influenced by secondary structures both 5' and 3' of the catalytic site. Nucleic Acids Research 26(14): 3433-42.