Document 0937
 DOCN  M9650937
 TI    Reciprocal relationship between stem-loop potential and substitution
       density in retroviral quasispecies under positive Darwinian selection.
 DT    9505
 AU    Forsdyke DR; Department of Biochemistry, Queen's University, Kingston,;
       Ontario, Canada.
 SO    J Mol Evol. 1995 Dec;41(6):1022-37. Unique Identifier : AIDSLINE
       MED/96139037
 AB    Nucleic acids have the potential to form intrastrand stem-loops if
       complementary bases are suitably located. Computer analyses of
       poliovirus and retroviral RNAs have revealed a reciprocal relationship
       between statistically significant stem-loop potential and sequence
       variability. The statistically significant stem-loop potential of a
       nucleic acid segment has been defined as a function of the difference
       between the folding energy of the natural segment (FONS) and the mean
       folding energy of a set of randomized (shuffled) versions of the natural
       segment (FORS-M). Since FONS is dependent on both base composition and
       base order, whereas FORS-M is solely dependent on base composition (a
       genomic characteristic), it follows that statistically significant
       stem-loop potential (FORS-D) is a function of base order (a local
       characteristic). In retroviral genomes, as in all DNA genomes studied,
       positive FORS-D values are widely distributed. Thus there have been
       pressures on base order both to encode specific functions and to encode
       stem-loops. As in the case of DNA genomes under positive Darwinian
       selection pressure, in HIV-1 specific function appears to dominate in
       rapidly evolving regions. Here high sequence variability, expressed as
       substitution density (not indel density), is associated with negative
       FORS-D values (impaired base-order-dependent stem-loop potential). This
       suggests that in these regions HIV-1 genomes are under positive
       selection pressure by host defenses. The general function of stem-loops
       is recombination. This is a vital process if, from among members of
       viral quasispecies, functional genomes are to be salvaged. Thus, for
       rapidly evolving RNA genomes, it is as important to conserve
       base-order-dependent stem-loop potential as to conserve other functions.
 DE    Base Sequence  Computer Simulation  Models, Theoretical  *Nucleic Acid
       Conformation  Polioviruses/*GENETICS  Recombination, Genetic
       Retroviridae/*GENETICS  RNA, Viral/*GENETICS  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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