“Our hypothesis is that before there were protein enzymes to make DNA and RNA, there were small molecules present on the pre-biotic Earth that helped make these polymers by promoting molecular self-assembly,” said Nicholas V. Hud, professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology. “We’ve found that the molecule ethidium can assist short oligonucleotides in forming long polymers and can also select the structure of the base pairs that hold together two strands of DNA.”
One of the biggest problems in getting a polymer to form is that, as it grows, its two ends often react with each other instead of forming longer chains. The problem is known as strand cyclization, but Hud and his team discovered that using a molecule that binds between neighboring base pairs of DNA, known as an intercalator, can bring short pieces of DNA and RNA together in a manner that helps them create much longer molecules.
“If you have the intercalator present, you can get polymers. With no intercalator, it doesn’t work, it’s that simple,” said Hud.
Hud and his team also tested how much influence a midwife molecule might have had on creating DNA’s Watson-Crick base pairs (A pairs with T, and G pairs with C). They found that the midwife used could determine the base pairing structure of the polymers that formed. Ethidium was most helpful for forming polymers with Watson-Crick base pairs. Another molecule that they call aza3 made polymers in which each A base is paired with another A.
“In our experiment, we found that the midwife molecules present had a direct effect on the kind of base pairs that formed. We’re not saying that ethidium was the original midwife, but we’ve shown that the principle of a small molecule working as a midwife is sound. In our lab, we’re now searching for the identity of a molecule that could have helped make the first genetic polymers, a sort of ‘unselfish’ molecule that was not part of the first genetic polymers, but was critical to their formation,” said Hud.
The work was supported by the National Aeronautics and Space Administration and the National Science Foundation.
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Nick Hud, Professor of Chemistry & Biochemistry and Associate Director of Georgia Tech's Institute for Bioengineering & Bioscience, has research on "Molecular Midwives" featured in Daily Times India.
Scientists at the Georgia Institute of Technology have discovered that small molecules could have acted as "molecular midwives" in helping the building blocks of life's genetic material form long chains and may have assisted in selecting the base pairs of the DNA double helix. "Our hypothesis is that before there were protein enzymes to make DNA and RNA, there were small molecules present on the pre-biotic Earth that helped make these polymers by promoting molecular self-assembly," said Nicholas V. Hud, professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology.
]]>In 2007, Georgia Tech was awarded a three year grant for a Phase I Chemical Bonding Center that is focused on understanding the chemical origins of the first biopolymers. I will discuss the scientific questions being addressed by center members, progress made within our first two years, and the expansion of the center as we prepare for a competition to become an NSF Phase II Center for Chemical Innovation.
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