MadSci Network: Molecular Biology

Re: Why the genetic code is read only in 5' --> 3' direction?

Date: Fri Mar 6 08:09:01 1998
Posted By: Paul Odgren, Instructor, Cell Biology, University of Massachusetts Medical School (Dept. of Cell Biology)
Area of science: Molecular Biology
ID: 888414636.Mb

Dear Man,
This is a question whose answer can only be opinion - informed opinion, 
hopefully, but I think it is opinion nonetheless. Let me give you mine, 
based on my own thinking. If I were you, I would run this question past 
some other people to get their ideas as well.

Not only is the genetic code read in the 5’-3’ direction, it’s also 
replicated in that direction. One strand (the leading strand) is copied 
linearly, and the other (the lagging strand) is copied in a series of short 
pieces (called Okazaki fragments after their discoverer) which are then 
ligated into a single long molecule. I suspect that the main reason DNA is 
both transcribed and replicated in the 5’-to-3’ direction is that if these 
processes could proceed in either chemical direction, you would obviously 
have a terrible problem. Genes encoded by DNA sequences would be ambiguous 
instead of specific and replication would be much more problematic if you 
could start at either end and/or go in either direction. While some 
organisms (especially in the viral world) may make use of both strands of a 
given stretch of DNA to encode proteins and even use "nested" sequences to 
read more than one message in different frames from a given sequence, they 
always follow only the 5’-to-3’ direction when reading or replicating the 
genome of that strand. 

Since reading and replicating in both directions wouldn’t work, evolution 
had to favor a system that was uni-directional. I’m not certain there are 
any inherent chemical advantages in going 5’ to 3’ rather than 3’ to 5’ 
that one could determine a priori, that is before the evolution of 
directional polymerases. I would guess that it just worked out that way 
based on some extremely early evolutionary events. The success of the 
directed use of DNA (or perhaps it was RNA in the primordial evolutionary 
events) then became locked into the evolutionary program by virtue of its 
success. In an analogous case, we have only the l-amino acids, not their 
d-isomers, used universally in protein synthesis by all of life. Again, no 
one is certain why one was "chosen" by evolution, but I believe it probably 
reflects another very early evolutionary solution to a serious problem of 

I hope this helps, and keep thinking!

Paul Odgren
Cell Biology
Univ. of Massachusetts Medical School
Worcester MA USA

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