Two Letters Added To The Genetic Alphabet

Scientists have determined the structures of two artificial DNA bases, Ds and Px, which have expanded the genetic code.

AsianScientist (Nov. 1, 2017) – In a study published in the journal Angewandte Chemie International Edition, scientists in Singapore and Germany have added two artificial letters to the genetic alphabet and revealed the molecular structure of the new base pair during DNA replication.

Just like how letters are strung together to form words, our DNA is also strung together by letters to encode proteins. The genetic alphabet contains only four natural letters—A, C, G and T—which are naturally bound together in base pairs of A-T and G-C. These specific base pair formations are essential in DNA replication, which occurs in all living organisms.

Genetic alphabet expansion technology is the introduction of artificial base pairs into DNA. In this study, researchers from the Institute of Bioengineering and Nanotechnology (IBN) of the Agency for Science, Technology and Research in Singapore have created a DNA technology with two new genetic letters that could be used in the detection of infectious diseases, such as dengue and Zika.

The two genetic letters, Ds and Px, were created by IBN Team Leader and Principal Research Scientist Dr. Ichiro Hirao and IBN Senior Research Scientist Dr. Michiko Kimoto in 2009. Ds and Px specifically combine with each other to form an artificial DNA base pair.

To obtain the molecular structure of the pair of new genetic letters, the researchers used X-ray crystallography, in which X-rays are passed through a crystal of the Ds-Px base pair during DNA replication. They found that the structure of the artificial base pair was strikingly similar to that of a natural base pair.

“The inspiration for the design of our new DNA base pair came from jigsaw puzzles, where complementary shapes fit together to form the specific pair,” said Hirao. “However, we did not know the actual molecular structure of our Ds-Px pair during DNA replication until this study with our collaborators at the University of Konstanz.”

Using this genetic alphabet expansion technology, IBN is developing DNA aptamers, which are modified DNA molecules that can bind to molecular targets in the body. The team plans to launch a test kit using these DNA aptamers to detect infectious diseases, such as dengue and Zika, in the next two years.

“The expansion of the genetic alphabet is a significant scientific achievement. It sheds insights into DNA’s natural replication mechanism, which will help us to design unique DNA molecules and technologies. For example, our technology can be used to create novel diagnostics and therapeutic agents with superior efficacy,” said IBN Executive Director Professor Jackie Y. Ying.

The article can be found at: Betz et al. (2017) Structural Basis for Expansion of the Genetic Alphabet with an Artificial Nucleobase Pair.


Source: A*STAR; Photo: Shutterstock.
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