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116   Melting DNA Yields Clues 
      To the Puzzle of Heredity
      The Washington Post, Saturday, September 21, 1968

     Until recently, crossbreeding was the only way biologists could
analyze the relationship of two forms with any real precision.

     From breeding studies, for example, we know that the amazing
range of varieties of dogs all belong to the same species -- only a
few genes differentiate the hairless Chihuaha from the St. Bernard --
while a vast gulf separates the cottontail form the European rabbit.
And as far as we know, the main species of higher primates cannot be
cross-bred, though it can hardly be said that exhaustive efforts have
been made with such combinations as the gorilla and the orangutan and
still more exotic combinations might eventually be proven to be cross-
fertile.

     The double-stranded structure of DNA, the substance within the
cells that controls heredity, opens the way to a completely different
approach to this problem.

     The DNA messages may be compared to the sentences of a book of
instructions.

     In the naturally occurring DNA molecules, the two strands are
held together by their mutually complementary structure: the same
message is encoded in each strand, but in two complementary 
languages, so to speak, which we might as well call "plus" and "minus."
If solutions of DNA are heated to some 158 degrees Fahrenheit,
the double strand structure melts and the strands separate.  If the
hot solutions are annealed -- that is, allowed to cool very slowly --
corresponding plus and minus strands may be able to find one another
and reform proper double strand molecules.

     Obviously, the chance that two corresponding strands can find
each other during the annealing will be much larger if most of the
molecules are similar to one another than if they fall into many 
different categories.  In terms of the book analogy, having many copies 
of the same sentence would make it easier to find matching pairs.

     Earlier studies on the annealing of DNA were done on simple
viruses and bacteria, about which we have a great deal of other 
information to help corroborate these ideas.  By labeling DNA from one 
species with isotopes, it was possible  to study the annealing of DNA 
from mixed melts with the DNA of another, a method of molecular 
hybridization that gave an alternative way of studying biological 
relationships.

     The first studies with higher organisms showed that the DNA of a
single species can be reannealed with ease that was surprising in view
of the expectation that it contained one to ten million different
kinds of DNA molecules.  On the other hand, even closely related 
species appeared to be very different by the criterion of molecular
hybridization.

     Recent reports by biochemists R. J. Britten and D. E. Kohne of the
Carnegie Institution of Washington and P. M. B. Walker of the University
of Edinburgh have helped to unravel this puzzle and raised striking
new ones.  A substantial part of the DNA in the cell nuclei of
vertebrates -- about 30 per cent in the mouse, somewhat less in man --
is of a highly repetitious character.  That is, the same sequence 
appears over and over again, a given family of DNA having anywhere ten
to a million duplicate molecules.  It is only this "repeated-sequence"
DNA that can reanneal rapidly under experimental conditions.  The rest
of the DNA conforms to previous expectations that it represents just 
one copy of each of the genes that can be recognized by traditional
breeding methods.

     The functions of this special DNA are at the moment quite 
mysterious,as are any reasons for it to differ  so markedly among rodent
species. (It still remains to be closely studied in primate species
and among the races of man.)  One speculation that cannot now be 
contradicted is that the special DNA is a residue of virus infections
that have played a hitherto unappreciated role in biological evolution.
When human cells are infected with SV-40 virus, at least 20 copies
pies of that DNA can be found in their progeny, in cell cultures.

     We have long known that salamanders have over ten times as much
DNA per nucleus as man.  We may now be relieved to hear that most of
this is a banal repetitious form and that man is still in the running
for being the species with the highest information content in his DNA.


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