Why Uracil?

Jeff Cohlberg cohlberg at csulb.edu
Wed Sep 25 19:50:30 EST 1996


taguebw at wfu.edu wrote:
: Roger J. Young wrote:
: In DNA, if a C deaminates to U, a repair system knows this is a wrong 
: as U does not occur in DNA but is replaced by T. (A C to U change can 
-: be see as a mistake without even resorting to the information on the 
: other strand of the DNA).
: So perhaps in the evolution of a more stable genetic storage system T 
: replaced U so that deaminations of C were more easily detected.

Absolutely correct.  The fact that U came first and T evolved later is
consistent with the fact that all four NDP's are converted to dNDP's by
ribonucleoside diphosphate reductase.  Then AFTER this conversion dUMP is
methylated to dTMP by thymidylate synthetase.  Clearly thymine nucleotides
came later in evolution than uridine nucleotides.

 : The hydroxyl group of
ribose does seem to have some steric effect
on : nucleic acid structure. I don't know if it is true, but Watson and 
: Crick suggested in their 1953 Nature paper "A structure for 
: deoxyribose nucleic acid" that the hydroxyl group of ribose may 
: sterically hinder RNAs ability to form nice long double helices like 
: DNA.

In fact, H-bonds involving the 2'OH of ribose play a major role in
stabilizing the tertiary structure of tRNA and (from what little is
known) other RNA tertiary structures as well.  I would say that DNA lost
the 2'OH in order make it harder for it to form complex globular
structures which would compete with double helix formation.  RNA's extra
OH gives it the capacity to form all these interesting structures, but
DNA's role in life is to be more content with (most of the time) forming a
boring old double helix.
Again, from a biosynthetic evolutionary point of view, ribonucleotides are
synthesized first.  Then all four NDP's are reduced to dNDP's by
nucleoside diphosphate reductase.  Clearly the reductase was a later
evolutionary development after the pyrimidine and purine nucleotide
biosynthetic pathways were already established.

Moral of the story -- all that boring metabolic biochemistry that we make
you cell biologists learn is really important and interesting after all!
-- 
Jeffrey A. Cohlberg, Professor
Department of Chemistry and Biochemistry
California State University, Long Beach
1250 Bellflower Boulevard, Long Beach, CA 90840
Phone: (310) 985-4944	FAX: (310) 985-8557   E-mail: cohlberg at csulb.edu



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