Gene expression

Diagram showing at which stages in the DNA-mRNA-protein pathway expression can be controlled

Gene expression is how the information in a gene (the sequence of DNA base pairs) is made into a product (such as a protein or RNA). The basic idea is that DNA is transcribed into RNA, which is then translated into proteins. Proteins make many of the structures and all the enzymes in a cell or organism.

Several steps in gene expression may be tuned. This includes both the transcription and translation stages, and the final folded state of a protein. Gene regulation switches genes on and off, and so controls cell differentiation, and morphogenesis. Gene regulation may also serve as a basis for evolutionary change: control of the timing, location, and amount of gene expression can have a profound effect on the development of the organism.

The expression of a gene may vary a lot in different tissues. That is how the tissues become different from each other. This is called pleiotropism. This term is important in genetics.

Epigenetics

In biology, epigenetics is the study of inherited changes in phenotype (appearance). Gene expression can be adjusted in ways other than the underlying DNA sequence. These changes may remain through cell divisions for the remainder of the individual's life, and may also last for more than one generation.

However, there is no change in the underlying DNA sequence of the organism.^[1] Instead, non-genetic factors cause the organism's genes to behave (express themselves) differently.^[2]

The best example of epigenetic changes in eukaryote biology is the process of cellular differentiation. Embryos start with their cells totipotent: they could become any tissue. . As embryos develop, their cells become specialised. They develop a particular function, and are part of an organ of the body. This is called morphogenesis. Epigenetic changes are long-term.

During morphogenesis, totipotent stem cells become the various cell lines of the embryo, which in turn become fully differentiated cells. In other words, a single fertilized egg cell – the zygote – divides and develops. The daughter cells change into the many cell types of the mature embryo. These include neurones, muscle cells, epithelium, blood vessels and so on.

This happens by activating some genes while inhibiting others.^[3]

Gene regulation

The structure of a eukaryotic protein-coding gene.

Up-regulation and down-regulation

Up-regulation increases the expression of one or more genes and so the protein(s) coded by those genes. Down-regulation is a process resulting in decreased gene and protein expression.

Induction vs repression

Gene regulation can be summarized as:

Inducible systems: an inducible system is off unless there is the presence of some molecule (called an inducer) that allows for gene expression.
Repressible systems: a repressible system is on except in the presence of some molecule (called a corepressor) that suppresses gene activity. The molecule is said to repress expression.

Regulatory RNAs

There are a number of RNAs which regulate genes, that is, they regulate the rate at which genes are transcribed or translated.^[4] The following are two important examples

miRNA

Micro RNAs (miRNA) act by joining an enzyme and blocking mRNA (messenger RNA), or speeding its breakdown. This is called RNA interference.

siRNA

Small interfering RNAs (sometimes called silencing RNAs) interfere with the expression of a specific gene. They are quite small (20/25 nucleotides) double-stranded molecules. Their discovery has caused a surge in biomedical research and drug development.^[5]^[6]

Gene Expression Media

An overview of the central dogma of molecular biochemistry with all unusual flows of information included (in green)
The process of transcription is carried out by RNA polymerase (RNAP), which uses DNA (black) as a template and produces RNA (blue).
Illustration of exons and introns in pre-mRNA and the formation of mature mRNA by splicing. The UTRs (in green) are non-coding parts of exons at the ends of the mRNA.
During the translation, tRNA charged with amino acid enters the ribosome and aligns with the correct mRNA triplet. Ribosome then adds amino acid to growing protein chain.
Protein before (left) and after (right) folding
The patchy colours of a tortoiseshell cat are the result of different levels of expression of pigmentation genes in different areas of the skin.
When lactose is present in a prokaryote, it acts as an inducer and inactivates the repressor so that the genes for lactose metabolism can be transcribed.
The lambda repressor transcription factor (green) binds as a dimer to major groove of DNA target (red and blue) and disables initiation of transcription. From PDB 1LMB.
In eukaryotes, DNA is organized in form of nucleosomes. Note how the DNA (blue and green) is tightly wrapped around the protein core made of histone octamer (ribbon coils), restricting access to the DNA. From PDB 1KX5.