The central dogma of molecular biology

Biology sounds like a really vast and complicated subject for many people. And in many ways, it is. However, a large part of the knowledge in biology, or at least in molecular biology, builds up from a very simple principle that we call “the central dogma of molecular biology”.

This central dogma was already outlined in 1957 by Francis Crick [1]. It is the theory that explains how life works, from tiny bacteria, through plants and animals, all the way to humans. There are differences among organisms, but the main idea is the same for everyone. We will talk about humans, just because it is easier to relate to that.

Our bodies are made up of cells. Your bones, your muscles, your brain, etc. are all formed of cells. Cells from different parts of the body can be quite different from each other (but that can be discussed in another post!). Nevertheless, they all have some basic components and one of them is the nucleus, which contains the DNA.

All the information that an organism needs to function is contained in these DNA molecules (or deoxyribonucleic acid molecules), so you can think of it as the instruction manual for the cells. It’s encoded with an alphabet of four letters that is enough to sustain all life forms! However, before being able to interpret the information, the cell needs to change it into a different, more accessible format: RNA (ribonucleic acid). The transformation from DNA to RNA is called transcription. You can think about it as “rewriting” a specific part of the manual that is needed at the moment and sending it out as an order or a task. Then, the RNA leaves the nucleus and is read by small molecules called ribosomes, which make proteins according to the instructions. The process of protein formation is called translation and can be understood as literally translating information from one language (DNA & RNA language) to another (protein language). Protein language consists of 20 “letters” known as amino acids. Assembled and folded amino acids make up proteins that carry out the actual work. For example, our muscles contract thanks to the action of two proteins (actin and myosin).

The central dogma of molecular biology was a revolution that changed the way we understand life [1]. For the first time, scientists understood relations among the most abundant molecules (DNA, RNA, and proteins). However, this theory was rather speculative at the time, and transcription and translation are more complex than our simplified version.

Crick, creating his theory, mentioned one exception – retroviruses (for example, HIV: human immunodeficiency virus). At that time he couldn’t have supported it with any evidence but it occurred to be true[1].

Retroviruses use RNA as their basic genetic material and they can copy the information from RNA into DNA, in a process called reverse transcription [2]. This process transforms viral genetic material (RNA) into the same type as ours (DNA).Thanks to that strategy virus and hijack the cell’s machinery and multiply itself.

Replication is a process of making two identical copies of DNA from one DNA molecule. As we grow, the number of cells in our body rises. For cells to do their job properly the instruction manual (DNA) must be transmitted to each new cell. Replication [3], [4] assures multiplying the number of DNA copies so that each cell can get one. The central dogma states that DNA is the main replicating molecule, although RNA can also be replicated (like in retroviruses, but the process could also play a role in humans [5]). According to Crick’s theory proteins are not replicable. Cells cannot make a protein-based on another protein – they always need RNA. Taken together, we can currently sum up the central dogma of molecular biology as follows (dashed lines indicate less common processes):

Biology is full of surprises and unexpected phenomena continue to appear. In some cases, their interpretation may seem to contradict the central dogma. For instance, the discovery of prions [6]: these incorrectly folded proteins can change the shape of already existing, “normal” proteins. They are responsible for many diseases [7], such as mad cow disease. Some scientists see it as a way to replicate information at the protein level [6]

Another example comes from epigenetics – field of science studying mechanisms controlling gene expression, without altering DNA sequence (you can picture it as giving or taking away access to some parts of our instruction manual). One of these mechanisms is proteins that can control the fragment of DNA that is actually expressed (i.e. used by the cell). It can be employed to argue that information can go backward in the original central dogma [8]. Nevertheless, the scientific consensus has not been reached yet, and the central dogma continues to be the key to our understanding of life at the molecular level. 

The central dogma is not only important for biology but also to understand the name of our blog! Just as some molecules in the cell transfer information from DNA, so that it can be understood by the ribosomes, we want to explain science in a simple way, so that it can be understood by everyone. Therefore, we see ourselves as the transcriptome (the set of all the RNA molecules inside the cell). The only difference is that instead of information from the DNA, we put science into an accessible format!

References:

 1.        Cobb, M. 60 years ago, Francis Crick changed the logic of biology. PLOS Biology 15 (2017).

2.         Fang, J.M.C.a.H. The Discovery of Reverse Transcriptase. Annual Review of Virology 3, 29-51 (2016).

3.         Cooper, G.M. in The cell: a molecular approach, Edn. 2nd (Sunderland(MA): Sinauer Associates, 2000).

4.         Pray, L.A. Major Molecular Events of DNA Replication. Nature Education 1 (2008).

5.         Ahlquist, P. RNA-Dependent RNA Polymerases, Viruses and RNA silencing. Science 296, 1270-1273 (2002).

6.         Reid, M.D.Z.a.C. A brief history of prions. Pathogens and Disease 73 (2015).

7.         Geschwind, M.D. Prion Diseases. Continuum (Minneapolis, Minn.) 21, 1612-1638 (2015).

8.         Koonin, E.V. Does the central dogma still stand? Biology Direct 7 (2012).

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