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more on sequence variations

Dave Knorr DAK at apldbio.com
Wed Dec 16 11:30:40 EST 1992

Back  to  Alex Jeffries questions    about  determining "the  correct"
sequence  of  a  given virus.   I   think   the  problem is especially
compounded  for  RNA viruses.    The  observation of a   sequence   is
different from an understanding of the biological significance of that
sequence.     The  previous  respondants to  the   post discussed  the
scientifically  prudent  steps to  take in reporting  a virus sequence
(i.e. are we  convinced that your  sequence is  reasonably accurate?).
The larger  question  remains what is the  biological activity of your
sequence?  Also, are  any of the variants contributing  to the overall
effect of the population?  Addressing  these  questions is not trivial
as even single site mutations can play a dramatic  role in the ability
of a given virus to survive.

An interesting point on error  rates in RNA  viruses: The  sequence of
tobacco mosaic virus, reported by a group  in England around 1982, was
assembled from small cDNAs.   In the  USA a couple  of years later, an
infectious clone was generated and found to be  virtually identical in
sequence.  The virus stock for  each  lab was probably originally from
the same source, but propagated  separately for  about 30  years.  Two
independently propagated populations of an  RNA virus (with supposedly
high  mutation  rates) maintained  the same   predominant sequence.  I
think there must also be  tremendous selection pressure on maintaining
an optimal sequence.

Dave Knorr
DAK at apldbio.com

P.S.  Hope the new news reader works

Dave (DAK) Knorr

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