Science News, May 28, 1994, page 349, reports: Tricks to make DNA beget DNA For scientists

_Science News_, May 28, 1994, page 349, reports:

                  Tricks to make DNA beget DNA

For scientists interested in how life came about, the 
chicken-and-egg controversy boils down to a question of 
molecular replication. Modern DNA molecules -- the stuff of 
genes -- encode information about other molecules, including 
enzymes that enable DNA to replicate, mutate, and evolve as 
conditions change. But how did DNA -- or perhaps RNA -- 
replicate before there were enzymes?

Several research groups already have mimicked many of the 
necessary steps for molecular evolution (SN 8/7/93, p91) in 
their atempt to re-create conditions leading to the origin of 
life. But in their experiments they make new copies of these 
molecules artificially, with enzymes helping.

Now, two groups have tricked small pieces of DNA into making 
copies by themselves, without enzymatic assistance. Both teams 
report their results in the May 19 _Nature_.

As a result of this work, "We are a step closer to 
understanding possible pathways to life," comments James Ferris 
of Rensselaer Polytechnic Institute in Troy, N.Y.

DNA and RNA are made up of long chains of nucleotides. In 
cells, each link in the chain readily pairs off with its 
complement: purines with pyrimidines and vice versa.

These connections give rise to DNA's typical structure -- a 
double- stranded helix -- which enzymes help split apart during 
cell division. The newly created single strands then act as 
templates. Each nucleotide seeks out a new partner, and these 
partners align to form a complementary strand, thereby creating 
two new double helices.

In test tubes, single purine nucleotides redily assemble on a 
pyrimidine template, but the reverse doesn't occur, so 
replication comes to a halt with mixed templates. Also, even 
when scientists could get molecules to replicate, those 
molecules could not make copies of their complements.

However, using DNA fragments with three nucleotides overcomes 
this obstacle, leading to the formation of complements on an 
ongoing basis, says Guenther von Kiedrowski from Albert-Ludwigs 
University in Freiberg, Germany.

For their experiments, von Kiedrowski and a collegue put 
nucleotide threesomes into a solution that also contained a six 
nucleotide strand. The matching threesomes then lined up to 
make a complementary six-nucleotide strand. This strand, too, 
began serving as a template for new strands.

Von Kiedrowski thinks that life's earliest molecules arose when 
small DNA fragments came together and served as templates for 
longer ones. Such fragments could have formed on clay 
substrates, adds Ferris.

Bigger nucleotide fragments also work, report Tianhu Li and 
Kyriaou C. Nicolaou, chemists at the Scripps Research Institute 
in La Jolla, Calif. They started with a palindromic sequence of 
24 nucleotides: The order of purines and pyrimidines reads the 
same from either end of the strand.

In a slightly acidic solution, a double-stranded DNA fragment 
attracted two shorter 12-nucleotide fragments, which assembled 
into a third 24-nucleotide strand upon the addition of a 
chemical reagent, the scientists report. Making the test-tube 
solution less acidic or adding more of the 12-nucleotide 
fragments causes that third strand to separate from the 
original double strand and to act as a template for a second 
stratnd complementary to itself.

"We're not saying that we've created life," says Nicolaou, "but 
this is perhaps the first example that molecules can replicate 
themselves without the help of enzymes."

Living systems expand exponentially: Two DNA strands beget 
four, which beget eight, then 16, then 32, and so on. Chemical 
systems increase incrementally, from one to to to three and so 
on. These new processes yield molecules at an in-between rate, 
say the scientists.