The bidirectional flow of information between the genome, transcriptome, proteome and metabolome, and how the complex interaction of components from the four functional levels and the environment produces the phenotype.
The complex interaction of the four functional levels in biological systems

How biochemicals interact with the environment to influence the phenotype

So far this week we have discuss how different components (metabolites and enzymes) interact in metabolism and how these interactions help us to investigate the function and phenotype of biological systems. We should also consider interactions with the genome and proteome. There are four biochemical or functional levels:

  • genome: the qualitative complement of DNA that encodes for all of the genes represented by both the coding and non-coding sequences of DNA.

  • transcriptome: the qualitative set of messenger RNA molecules transcribed from the genetic code of the genome

  • proteome: the complete set of proteins translated from messenger RNA

  • metabolome: the complete complement of metabolites that are present in a biological system

The four functional levels provide us with complementary information:

  • the genome provides us with information on what may happen; it is static and is influential during the process of transcription to construct RNA molecules

  • the transcriptome and proteome are dynamic and tell us what is happening

  • the metabolome is also dynamic and tells us what has happened

The genotype is the genetic instructions inherited and encoded in the genome. These instructions produce a wide range of characteristics and functions including the colour of your eyes and how your heart operates. The genome is ‘relatively’ stable but genes are subject to regulatory processes. For example, the methylation of genes by epigenetic processes can switch genes ‘on’ or ‘off’.

The environments in which we live, as well as our lifestyles, influence how we function. For example, an individual who cycles 100 kilometres each week will operate with a much healthier function than someone who has an unhealthy and unbalanced diet and does not exercise. Unlike the genome, the environment and our lifestyles are dynamic and periodically change. For example, we may exercise only at weekends and not during the working week. Our environments and lifestyles are different during the week at work compared to the weekend when we relax and enjoy our hobbies.

The phenotype is defined as the physical and biochemical characteristics of an organism as determined by the interaction of its genetic constituents and environment, and for humans their lifestyle. The phenotype is also dynamic. For example, the concentration of metabolites detected in urine are different before and after we undertake strenuous exercise. One change is an increase in the concentration of lactic acid which is produced by anaerobic respiration in muscles. Lactic acid is the metabolite which makes our muscles ache when its concentration increases in muscles during exercise. The metabolome is the furthest downstream product of the genome and its interaction with the environment and is therefore considered to provide a direct and sensitive measure of the dynamic phenotype at the molecular level – the metabolome defines what has just happened.

There are various levels of interaction in biological systems with feedback and feed-forward loops regulating the molecular interactions that influence the cellular phenotype. These include interactions both within and between the functional levels. One example of interactions between two functional levels is metabolism, where metabolites are metabolised in the presence of an enzyme (and often a cofactor). An example of an interaction within one functional level is protein-protein interactions that occur in the proteome. Here two or more proteins physically interact and form a single multi-protein complex which provides greater efficiency in the synthesis of metabolites, either through the consumption of less energy or a higher rate of synthesis. Through this approach multiple metabolic enzymes can collaborate and work together to synthesis a metabolite or metabolites.

Probably the most frequently used example of interactions which regulate a biological system is the regulation of the lactose operon in the bacteria Escherichia coli. Glucose is the preferred fuel source in E. coli and so in the presence of glucose the enzymes for the catabolism of the alternative carbon source lactose are not activated and the transport proteins used to transport lactose into the cell are inactive. However, when glucose levels are low the lactose operon and lactose transporters are no longer switched off and are instead switched on and lactose is used as an energy source.

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This article is from the free online course:

Metabolomics: Understanding Metabolism in the 21st Century

University of Birmingham