365: Chemistry for Life
DAY 147

Deciphering the Genetic Code

Scientists decipher the genetic code in 1961 experiment using Synthetic RNA, showing how messenger RNA transcribes genetic information from DNA.

Credit: NIH

Interpreting the language of the genetic code was the work of Marshall Nirenberg and his colleagues at the National Institutes of Health. Their careful work, conducted in the 1960s, paved the way for interpreting the sequences of the entire human genome.

After Nirenberg and Matthaei “cracked” the first “word” of the genetic code, scientists raced to translate the unique code words for each amino acid in hopes of someday reading the entire genetic code of living organisms. Nirenberg assembled a team of about twenty researchers and technicians.

Using the poly-U experiment as a model, Nirenberg and his colleagues identified nucleotide combinations for the incorporation of other amino acids. The researchers found that the coding units for amino acids contain three nucleotides (a triplet). Combining four nucleotides in three-letter codes yielded 64 possible combinations (4 x 4 x 4), sufficient to describe 20 amino acids.

They discovered the codes for other amino acids: for example, AAA for lysine and CCC for proline. Replacing one unit of a triplet code with another nucleotide yielded a different amino acid, for one example, synthetic RNA containing one unit of guanine and two of uracil (code word: GUU) caused incorporation of valine.

In 1964 Nirenberg and Philip Leder, a postdoctoral fellow at NIH, discovered a way to determine the sequence of the letters in each triplet word for amino acids. By 1966 Nirenberg had deciphered the 64 RNA three-letter code words (codons) for all 20 amino acids. The language of DNA was now understood and the code could be expressed in a chart.

Visit National Historic Chemical Landmarks to continue reading about the deciphering of the genetic code.

Excerpted with permission, National Historic Chemical Landmarks Program
www.acs.org/landmarks