In the intricate world of genetics, where the alphabet consists of just four letters representing nucleotides, scientists have long pondered the possibility of expanding this code. The quest to add more letters to the genetic alphabet has taken a significant step forward, as researchers at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have made a groundbreaking discovery.

Figure 1. Synthetic Nucleotide. (Credit: UC San Diego Health Sciences)

The Breakthrough

Published on December 12, 2023, in Nature Communications, the research reveals that RNA polymerase, a crucial enzyme in protein synthesis, can recognize and transcribe artificial base pairs in the same way it does with natural pairs. This finding opens up new possibilities for creating custom proteins, potentially revolutionizing medicine.

The Significance

Senior author Dong Wang, PhD, emphasizes the potential impact of this discovery, stating, "Expanding the genetic code could greatly diversify the range of molecules we can synthesize in the lab and revolutionize how we approach designer proteins as therapeutics." With life on Earth currently relying on just four nucleotides (adenine, thymine, guanine, and cytosine), the prospect of adding more letters to the genetic code is both tantalizing and promising.

The Study's Approach

The researchers utilized a modified genetic alphabet known as the Artificially Expanded Genetic Information System (AEGIS), which incorporates two new base pairs. AEGIS, initially developed as a NASA-supported initiative, aimed to understand the potential development of extraterrestrial life. By isolating RNA polymerase enzymes and testing their interactions with synthetic base pairs, the team observed that the enzymes couldn't distinguish between synthetic and natural base pairs.

Structure Determines Function

In the world of biology, structure is a critical determinant of function. Wang explains, "By conforming to a similar structure as standard base pairs, our synthetic base pairs can slip in under the radar and be incorporated in the usual transcription process." This opens the door to a wide array of possibilities in synthetic biology.

Supporting an Old Hypothesis

The findings also lend support to the tautomer hypothesis, dating back to Watson and Crick's original discovery. This hypothesis suggests that the standard four nucleotides can form mismatched pairs due to tautomerization, providing a source for genetic mutations.

Future Endeavors

Looking ahead, the researchers plan to explore whether their observations hold true for other combinations of synthetic base pairs and cellular enzymes. Wang expresses excitement about assembling a collaborative team to delve into the molecular basis of transcription with an expanded genetic alphabet.

As scientists continue to unlock the secrets of synthetic DNA, the potential to expand the genetic alphabet opens new doors for scientific discovery and medical advancements. The ability to create custom proteins may lead to innovative medicines, marking a significant milestone in the field of genetics.

Source: University of California - San Diego

Cite this article:

Hana M (2023), Unleashing the Power of Synthetic DNA: Expanding the Genetic Alphabet, AnaTechmaz, pp. 246