A New Dogma Of Molecular Biology: A Paradigm Shift

Thomas Kuhn, in his groundbreaking e book The Structure of Scientific Revolutions, described a paradigm shift in science as a brand new understanding of nature that:

1. Is a sufficiently unprecedented principle to draw an everlasting group of adherents.
2. A principle that’s open-ended with many issues for the redefined group of practitioners to resolve.

This is exactly the character of our new understanding of biology, which has occurred over the previous twenty years and is now sufficiently superior to supply a brand new paradigm.

The earlier paradigm was given in what is known as the central dogma.

DNA—> RNA—> Protein—> Phenotype

The dogma was enshrined in Jim Watson’s 1965 epic textbook The Molecular Biology of the Gene.

The principle holds that Gregor Mendel’s idea of a gene (a discrete heritable trait or phenotype) is the consequence of a change within the textual content of DNA that alters the operate of a protein and, subsequently, the phenotype. Sickle cell anemia is a primary instance. A single-letter change within the DNA that encodes the hemoglobin protein adjustments the construction of the protein in order that it aggregates to create sickle-shaped purple blood cells, resulting in the blood clots that outline the illness. While true, we now view this paradigm as a particular case of a broader actuality. Why?

Anomalies

There is a necessity for a brand new paradigm to account for a sequence of anomalous observations.

Over the previous twenty years, we have now made spectacular progress in studying the entire genome sequences of lots of of hundreds of people and tens of hundreds of different species. We have uncovered numerous variations amongst people of their inherited DNA sequence and related these adjustments with hundreds of inherited traits, together with inherited illnesses.

An enormous shock: The overwhelming majority of adjustments in DNA sequence of consequence will not be within the 2% of the human genome that specify proteins however fairly within the 90% or extra of the genome that doesn’t. In different phrases, most of what Gregor Mendel described as a trait is normally NOT a change within the sequence of a protein.

If most genes will not be proteins, what are they?

Another revelation has additionally emerged from genomic research. Recent research reveal that animal and plant cells copy the good majority of DNA into RNA. Humans copy at the very least 70% of our genome into RNA, vastly greater than the two% specifying protein. Previously, non-protein coding DNA was associated to a trash heap known as “junk DNA”. Additionally, many variants that have an effect on heritable traits happen in different non-protein-coding regulatory areas, together with RNA transcription begin, cease, and splicing sequences.

A 3rd anomaly has been obvious for a while. Very easy organisms possess variations of the good majority of the twenty thousand proteins much like these of complicated animals, together with us. How will we account for the complexity of most multicellular organisms and ourselves?

In the early days of molecular biology, the universality of the genetic code prompted the Nobel Prize-winning biologist Jaques Monod to proclaim, “What is true for phage lambda is true for the elephant.” Elucidating the human genome and people of different species revealed an infinite complexity within the group of DNA and RNA not evident in viruses or micro organism.

A New Paradigm

We are actually within the midst of a really thrilling revolution defining what function this new view of DNA and the plethora of RNAs play in defining our biology. A consensus is now rising as a brand new organic principle. Whereas our twenty thousand proteins carry out the required capabilities for all times, it’s the RNA, made principally from the “junk DNA,” that controls when and the place proteins are made.

I describe this new paradigm because the DNA/RNA Dogma, an outline that assigns equal significance to each DNA and RNA, a concentrate on the management of protein expression as a key to understanding Mendelian inheritance. The DNA/RNA Dogma gives a extra complete and correct image of Mendel’s genes and our complexity.

The new dogma now reads.

DNA <—> RNA—> Control—> Protein—> Phenotype

The insertion of the phrase “management” denotes our quickly increasing data of the function RNA performs in controlling when, the place, what number of, and in what kind proteins are made.

The new double arrow between DNA and RNA describes each the RNA-directed modification of DNA that impacts RNA manufacturing and the reverse circulation of genetic data from RNA not accounted for by the unique central dogma. Like all diagrams, this one is oversimplified. For instance, some non-coding RNAs have an effect on phenotype.

Analogy could assist. I now have intensive expertise with Lego in constructing total cities for my grandchildren. Lego units include a set of coloured plastic elements and a set of directions to assemble them. In this analogy, the plastic elements are the proteins, restricted in quantity, every with an outlined kind. The directions are the regulatory RNAs. With the identical elements, you’ll be able to construct both a easy or complicated construction. Change the directions, and you modify the construction. A single error within the directions (or a lot much less often in a constructing block) ends in a fault within the closing construction. There are many extra phrases within the directions than there are within the several types of constructing blocks. Most organisms produce very comparable units of proteins however differ markedly in the best way these proteins are used. Kits for complicated buildings, like Ninjago units, additionally embody a minority of personalized blocks analogous to specialised proteins.

The new Dogma meets Thomas Kuhn’s definition of a paradigm shift.

1. The DNA/RNA Dogma is sufficiently unprecedented to draw an everlasting set of adherents. Indeed, many new research elaborating on the invention and particulars of recent regulatory RNAs and genome buildings are revealed every week.
2. T. he DNA/RNA Dogma is open-ended, with many issues to be resolved. The weekly accumulation of recent discoveries highlights this principle’s open-ended nature.

I liken the shift to the DNA/RNA Dogma as akin to the paradigm shift between Newtonian physics and quantum principle. Newtonian physics defined a lot of what was then recognized in regards to the bodily world. Newtonian physics isn’t incorrect, however it is just a particular case that applies to massive objects. The authentic central dogma defined a lot of what was recognized about easy organisms, viruses, and micro organism however didn’t clarify the biology of complicated organisms.

New theories should not solely clarify huge new units of observations and predict future observations, however they need to even be accepted by most practitioners and the general public. Thanks to COVID-19 RNA vaccines, the latest appreciation of the significance of RNA is now typically understood by the general public. RNA biology is now additionally on the forefront of gene remedy, gene modifying, and most cancers therapies.