How the process of so called “gene expression” proceeds?

 

We call gene expression the set of reactions that exploits information from a gene to control the abundance of proteins inside the cell. Its basic steps consist of gene activation, the transcription of DNA to “messenger” RNA (mRNA) and the translation of the information carried by mRNA into proteins. In particular, transcription is mediated by a type of proteins, known as Transcription Factors (TFs), which move randomly through the cell and bind to a portion of DNA, the promoter region. If it is in an activated state, the production of a corresponding string of mRNA is initiated and leads to the synthesis of new proteins. Chemicals interacting for some cellular function are said to belong to a “biochemical network”, as one can visualize molecules as nodes and chemical reactions as links between them. In this level, you will explore how this chain of biochemical processes might become subject to random fluctuations. They arise as the result of random motions and random encounters between molecules: cells in fact are very crowded environments!

 

 

 

What creates the parrot's colouration patterns?

 

The parrot's feather coloration pattern doesn't look like a perfect copy of its parents' one, with whom it shares the genetic heritage. Genetic differences occur due to a re-arrangement of DNA during the reproduction (“crossover”) and unpredictable mutations. In general, patterns of pigmentation in multicoloured animals is not controlled only by their set of genes (“genotype”) but also the history and the environment contribute to their variability. Even if we could select the same genes, follow the same history, expose cells to the same environment, still organisms would display some difference in their observable features (“phenotype”). Scientists have recently thought that randomness in the process of gene expression can be a major source of phenotype variability.

It means that, if molecules of a specific type exist in few copies inside a cell, random effects stemming from their random walks can become important. What does it imply at the end of the day? Every individual in a population of living organisms is unique and differs from anyone else, even its twin or clone, in appearance and behaviour.

 

 

 

 

Transcription Factors' Random Walk

 

During gene expression, TFs perform a random walk through the cell before reaching their specific promoter region. The space available to this motion is limited by the overall arrangement of internal cellular structures, i.e. organelles. The presence of such “constraints” controls the randomness of TFs' walk by directing it towards the region that must be activated.

The successive process of mRNA creation is itself a “probabilistic” one, in the sense that we cannot predict exactly how it will happen but we can only define a “probability”, i.e. a degree of likelihood, for it. Typically it depends on the quantity of TFs binding through some mathematical formula derived from experimental data. The intuition beyond can be summarised as: “the more TFs bind to the promoter region, the more likely and the more abundant becomes mRNA production”. As a few TFs, RNA and DNA molecules are present inside a cell, random jumps may significantly modify their number and thus affect the visible pattern they control, e.g. colours.

 

 

Networks and Noise

 

Molecular species involved in gene expression form a network, whose links are chemical reactions. Models used in this context are thus often referred to as "Random Walks on Networks".

The parrot's feather coloration pattern is not controlled only by its set of genes (“genotype”) but also the history and the environment contribute to its variability. Even if we could select the same genes, follow the same history, expose cells to the same environment, still organisms would display some difference in their observable features (“phenotype”). Biologists refer to variation in measured levels of gene expression products (e.g. proteins) as “noise”, regardless of the source. They call “extrinsic” the noise due to microscopic cell-to-cell differences of environment and history, “intrinsic” the one due to random fluctuations. We have seen how various steps in gene expression can be “noisy”, i.e. affected by random fluctuations: should they be considered errors in the machinery of life? Random fluctuations can be advantageous from the evolutionary point of view. Variation provides the flexibility needed by organisms to adapt to sudden changes in the environment, thus to survive. In this perspective, diversity is at the core of life.