DNA size a crucial factor in genetic mutations, study finds

Oct 26, 2005

Researchers at Stanford University have created a larger-than-normal DNA molecule that is copied almost as efficiently as natural DNA. The findings, reported in the Oct. 25 online edition of the Proceedings of the National Academy of Sciences (PNAS), may reveal new insights into how genetic mutations-tiny mistakes that occur during DNA replication-arise. The discovery was made in the laboratory of Eric Kool, a professor of chemistry at Stanford and co-author of the PNAS study.

DNA, the genetic encoder of life, comes in two parallel strands that form a double helix. It's like a long, twisted ladder where each rung consists of two molecules that form a base pair. DNA has four bases: adenosine (A), thymine (T), guanine (G) and cytosine (C). A always pairs with T, and G with C. To copy itself, the DNA molecule unwinds and splits. Either strand is now a template to build a new DNA molecule. An enzyme-a protein that speeds the reaction, in this case the bacteria E. coli's DNA polymerase I-moves along the template and selects the corresponding base to create a new base pair.

DNA bases fit into a specialized site on the enzyme before they are bonded to the template. Kool wanted to see how the enzyme reacts if the bases are not the usual size. ''The idea was to see how DNA replication depends on size,'' Kool says.

The researchers investigated it by offering bases of different sizes to the DNA polymerase I enzyme and measuring how accurately the enzyme made new DNA copies. About once every 10,000 to 100,000 times the enzyme will put in the wrong base, choosing for instance a G instead of a T to pair with an A. The rate that the enzyme accurately copies DNA is known as its efficiency.

These rare and random mistakes can cause genetic mutations. While we tend to heap negative connotations onto the term, some mutations create new traits that actually benefit the organism or yield no effect. These small-scale changes, collectively called genetic drift, play an important role in evolution, as does natural selection.

To make their DNA bases, Kool started with a molecule similar to thymine-called an analog-and made five different sizes by adding increasingly larger atoms. The first analog was smaller than natural thymine, the second about the same size and the last three were increasingly larger. The difference between the smallest and largest analogs was only one angstrom, or a tenth of a nanometer.

Bigger is better

When the researchers offered the analog bases to DNA polymerase I, the enzyme not only recognized the synthetic molecules as it would natural DNA but also copied one of the slightly larger analogs at a rate 22 times more efficiently than the natural-sized analog. In fact, DNA polymerase I incorporated the slightly larger analog almost as efficiently as it did natural thymine, both in the test tube and in live E. coli bacteria. In contrast to this, the smallest and largest analogs in the set were rejected by the enzyme and the bacteria.

According to Kool, these results indicate that size is a strong factor determining enzyme efficiency-and a mechanism for allowing mutations into the DNA molecule.

''It's a way the organism can evolve,'' Kool says. ''If the protein that copies DNA prefers a molecule that's slightly bigger than natural DNA, then it can accept mistakes more readily.'' For example, although T is supposed to match up with A, it might be inclined to pair with G, which has a slightly larger configuration.

The sheer fact that a living system readily used a base-or nucleotide-that was artificially created is itself groundbreaking. ''Here we have, I think, the first example of an efficient, human-designed nucleotide working in a live cell,'' he says.

Kool and the gang are now exploring ''the funny finding that the bugs prefer DNA that's larger than natural DNA'' by making larger nucleotides. ''Size and shape are related issues, so we're interested now in keeping the size constant and changing the shape,'' Kool adds.

Source: Stanford University

Explore further: The nostalgia effect: Do consumers spend more when thinking about the past?

add to favorites email to friend print save as pdf

Related Stories

Bitcoin 'mining pool' promises to stay small

47 minutes ago

The largest group of bitcoin miners, which maintains and processes transactions in the digital currency, is promising to avoid majority control of the currency as a temporary measure to maintain the payment system's credibility.

Airbnb remodels online home

57 minutes ago

Online lodgings listings service Airbnb on Wednesday took the wraps off a major remodel of its online home complete with a new logo.

Can Modi clean the Ganges, India's biggest sewage line?

1 hour ago

Standing on the banks of the river Ganges a day after his election triumph, Prime Minister Narendra Modi vowed to succeed where numerous governments have failed: by cleaning up the filthy waterway beloved ...

Bing offers to 'forget' links in Europe searches

1 hour ago

Microsoft on Wednesday followed in Google's footsteps by letting people in Europe ask to have links related to them 'forgotten' on its search engine Bing, under the auspices of a court ruling.

Really smart cars are ready to take the wheel

1 hour ago

Why waste your time looking for a place to park when your car can do it for you? An idea that was pure science fiction only a few years ago is becoming reality thanks to automatic robot cars.

Recommended for you

P90X? Why consumers choose high-effort products

9 hours ago

Stuck in traffic? On hold for what seems like an eternity? Consumers often face situations that undermine their feelings of control. According to a new study in the Journal of Consumer Research, when a person's sense of con ...

Overdoing it: Multiple perspectives confuse consumers

9 hours ago

Television commercials for luxury vehicles pack a lot in their 30-second running times: the camera offers quick shots of the soft leather upholstery, the shiny colors, the state-of-the-art entertainment system, ...

User comments : 0