The Genetic Code: The most fundamental concept in all biology.
Shortly after the discovery of the structure of DNA by Watson and Crick, scientists
were faced with a significant problem: How does the information encoded in DNA
get translated into a protein.
In 1954, our old friend Francis Crick hypothesized that there had to be an “adapter
molecule” … the go-between from DNA to Protein. His adapter molecule was later
discovered. We call it transfer RNA (tRNA).
In 1955 (the year of my birth), a Russian physicist named George Gamow (“gam
off”) put forth a challenge to decipher the genetic code. There are 4 bases in DNA
and 20 amino acids. So Gamoff got 24 top scientists in biology, chemistry, physics,
and math to join the “RNA Tie Club.” Really. Twenty were assigned one of the
amino acids, 4 were assigned one of the nucleotides. (Watson and Crick were
members.) They actually had ties with a double helix on them…designed by Gamow
himself. Imagine what one of those ties would be worth today.
The Tie Club members figured (rightly) that it would take 3 consecutive nucleotides
to code for one amino acid. Since one could only code for 4 amino acids (41=4), and
two nucleotides could only code for 16 amino acids (42=16), then it would take at
least 3 nucleotides to code for 20, with some 3-letter codes to spare (43=64). So
with that part solved, the question became…what are the 3-letter codes (codons) for
each of the 20 amino acids?
Ironically, a non-member developed the technique for cracking the code. His name
was Marshall Nirenberg. The year was 1961. His technique involved making
synthetic RNA molecules. Note: A rarely-mentioned woman scientist, Maxine
Singer, figured out how to make the synthetic RNAs. The first one was a RNA
molecule of UUUUUUUUUUUUUUUUUUU…. When Nirenberg put this poly-U RNA in
the mix with all 20 amino acids, he got a polypeptide consisting of the amino acid
phenylalanine (phe) and nothing else. Recall that in RNA, Uracil replaces Thymine.
Using Nirenberg’s technique, other scientists finished working out the “codon
assignments” for all 64 possible codons. You see this masterpiece of scientific
achievement humbly represented on page 237 in your text. It looks so simple at a
glance, but it is a masterpiece. To see why, one must look deeper.
The code is optimized in several ways. First of all, it has built-in mutation
mitigation. Secondly, it is optimized in a way that actually facilitates evolution.
Modern scientists are still working on how such a code could have evolved. As a
part of their efforts, the attributes of the code (error mitigation; facilitating
evolution, etc) were used to create algorithms and computer models to develop
alternate codes that were equally efficient. Many different codes were produced in
this way, but none were more exquisitely optimized than the one given to us by
nature.
Perhaps the most mind-boggling discovery was the universal nature of the code. All
life uses the same code. On the surface that doesn’t make sense, but it did/does
raise some fascinating questions. It now appears that the Universal Genetic Code is
critical for evolution. There’s more to evolution than Darwin’s “Descent with
Modification.” Organisms exchange genes via Horizontal Gene Transfer (HGT), and
if a lineage were to deviate in its codon assignments, then it would be rendered
illiterate…a huge disadvantage, apparently a lethal disadvantage since no organism
(or virus) uses a different code. Some scientists would point out that there are
actually some very minor modifications, but none that would be any more
significant that say American English vs British English.
The implication of the universality of the code is that it had to have evolved along
with the very first cells (3.8 billion years ago). Since the code is essentially a
language, and since languages develop and evolve communally, we can infer that the
genetic code formed within a community of entities that no longer exists (as far as
we know). Once the code “gelled”, cellular life took off, ultimately branching into 3
great lineages; Bacteria, Archaea, and Eukarya. Different as these lineages may
seem, they all live by the same code. They all use ATP. They all need glucose. They
all have the same DNA that codes for the same 20 amino acids. And on and on. Such
is the unity of life. To me, every bit as interesting as the diversity of life.