Vanderbilt biochemist Martin Egli, Ph.D. is trying to make sense of evolution of DNA by studying its chemistry. He asks some very interesting questions:
One particular curiosity: how did DNA and RNA come to incorporate five-carbon sugars into their “backbone” when six-carbon sugars, like glucose, may have been more common? Egli has been searching for the answer to that question for the past 13 years.
Recently, Egli and colleagues solved a structure that divulges DNA’s “sweet” secret. In a recent issue of the Journal of the American Chemical Society, Egli and colleagues report the X-ray crystal structure of homo-DNA, an artificial analog of DNA in which the usual five-carbon sugar has been replaced with a six-carbon sugar.
By exchanging the sugars that make up the DNA backbone, researchers can make and test plausible “alternatives” to DNA — alternatives that nature may have tried out before arriving at the final structure. These alternative structures can then reveal why DNA’s genetic system is more favorable than the other possible forms…
While the homo-DNA structure shows a number of similarities with DNA, it is much more stable than DNA. However, it has a more haphazard appearance than normal DNA, looking more like a “slowly writhing ribbon” than the tightly twisted ladder of DNA.
“The reason that DNA was ‘picked’ is not because it’s thermodynamically extremely stable,” Egli said. “There are others — including homo-DNA — that are actually superior in that regard.”
Egli’s structure also shows that homo-DNA has more flexibility in how the bases (rungs of the ladder) bind. The bases in normal DNA adhere to a somewhat strict binding scheme — guanine (G) binds with cytosine (C) and adenine (A) binds with thymine (T). In this “Watson-Crick” base pairing, the G:C bonds are much stronger than A:T or any other bonds.
“In homo-DNA, the Watson-Crick base pairing rules are changed,” Egli said. “For example, G:C is similar to G:G or A:A, so you have a much more versatile pairing system in homo-DNA. Therefore, the nature of the sugar in the backbone affects the pairing rules.”
But despite homo-DNA’s apparent versatility in base pairing and its thermodynamic stability, other features of the molecule’s architecture probably preclude it from being a viable genetic system
For example, it cannot pair with other nucleic acids — unlike DNA and RNA which can and must pair with each other. Also the steep angle, or inclination, between the sugar backbone and the bases of homo-DNA requires that the pairing strands align strictly in an antiparallel fashion — unlike DNA which can adopt a parallel orientation. Finally, the irregular spaces between the “rungs” prevent homo-DNA from taking on the uniform structure DNA uses to store genetic information.
The findings suggest that fully hydroxylated six-carbon sugars probably would not have produced a stable base-pairing system capable of carrying genetic information as efficiently as DNA.
While the homo-DNA structure shows a number of similarities with DNA, it is much more stable than DNA. However, it has a more haphazard appearance than normal DNA, looking more like a “slowly writhing ribbon” than the tightly twisted ladder of DNA.Read on at Vanderbilt’s Reporter…