The
Central Dogma of Molecular Biology
The 1950s witnessed an explosion of groundbreaking
discoveries in the biological sciences, the most central of which was the
discovery of the molecular structure of DNA, deoxyribonucleic acid. Commonly
credited to James Watson and Francis Crick, the double helix discovery saw
contribution from Rosalind Franklin and Maurice Wilkins, the latter of whom
were included in the three-way split of the Nobel Prize rewarding their
discovery. Franklin tragically passed away at the age of 37, and could not be
awarded the Nobel Prize, which is not given posthumously.
The double helix itself consists of a
sugar-phosphate backbone, each unit of which is attached to a nucleobase;
adenine, cytosine, guanine or thymine. Each base attached to the ribose sugar
and phosphate group is known as a nucleotide. The amount of adenine is equal to
tyrosine, and likewise with cytosine and guanine, a property that was
discovered by Erwin Chargaff. It follows that adenine always binds to tyrosine,
and cytosine to guanine. Each nucleoside acts like a letter in the code with
which life is written. The binding pattern and shape of the helix allows the
two strands to separate, and for each strand to act as a template for the opposite
strand to be synthesised. Thus, the discovery of the DNA structure allowed an
understanding of the way in which DNA is replicated.
(From Wikipedia)
DNA serves as the blueprint of life, and is copied
virtually unchanged as cells divide. It also serves as the template with which
proteins are made, using another code of amino acids. However, it was long
known that eukaryotic proteins are formed in the cytoplasm of a eukaryotic
cell, while DNA resides in the nucleus. Therefore, an intermediate molecule,
known as messenger RNA (mRNA), exists to bridge this gap. The central dogma of
molecular biology, then, as it was dubbed by Crick, describes the process by
which DNA is replicated, transcribed into RNA, and translated to produce
proteins, the building blocks of life and the molecular machines which carry
out the functions required by the body.
An idea often repeated by the general public is that
out of 3 billion base pairs of DNA in each of our cells, only 3% are
functional, while the remaining 97% are referred to as “junk”. Formally the protein-coding regions are known
as exons, while the bits in-between are introns. A single gene comprises of one
or more exons interspersed by introns, which are spliced out
post-transcription.
Why such a system exists is rather uncertain. The
reasons include a variety of things such as the fact that exons appear to be
able to be differentially spliced, producing different proteins. Thus a smaller
amount of DNA is capable of producing the complexity of the human body. Another
is that certain DNA elements known as transposons are able to relocate
themselves into other regions of the chromosome. These so-called jumping genes
find a tract of unused DNA and settle there. Natural selection ensures
unfavourable transposon relocations, i.e. those that disrupt gene codes, do not
persist. In fact, the accumulation of non-essential DNA could perhaps reduce
the likelihood that functional DNA is damaged. What is becoming more and more
certain is that many regions of DNA previously thought to be “junk” in fact do
have a role.
These non-coding DNA are transcribed into RNA which
do not ultimate serve as a protein template. Some of their functions have been
known for decades, such as transfer RNA, ribosomal RNA and regulatory RNA.
Increasingly, non-coding RNA transcripts are being found to somehow affect the
levels of transcription of the protein-coding RNA. These act as fine-tuning
mechanisms that can dictate when and where to produce more of a protein, and
how much. Often they are affected by environmental cues, which are also
important in ordering the direction of growth for organisms.
Epigenetic effects, which are modifications to DNA
which does not alter its nucleotide sequence, are also important in affecting
the way proteins are expressed. Each cell in our body contains the same DNA,
yet different types of cells transcribe different RNA and thus produce
different proteins. Modifications such as DNA methylation are responsible for
highlighting which genes should be turned on or off in a cell, and these are also
inherited as cells replicate. The structure with which DNA are packaged in
chromosomes, by means of chromatin packaging, is also involved. DNA is wound
tightly around protein complexes called histones, which inhibit the DNA from
being transcribed, unless an unwinding process occurs.
So this is the means by which DNA serves as the
genetic code upon which all life is written. DNA is transcribed into RNA, which
is translated into amino acids, with the help of other RNA molecules and
proteins which act on transcripts. These amino acids form the proteins which
serve as the structural and functional backbone of all living creatures.
