Genetic Regulatory Networks

AMATH 882

Lecture 7, Feb 2, 2011

DNA (deoxyribonucleic acid) consists of a deoxyribose chain along which are attached four distinct bases (referred to as A,C,G, and T). The genetic content of an organism is contained in the sequence of bases in its DNA molecule(s).

http://genetics.gsk.com/graphics/dna-big.gif

http://www.biologycorner.com/resources/mRNA-colored.gif

In addition to DNA, another set of nucleic acids, ribonucleic acids (RNAs) play a key role in expressing the content of the genome. RNAs are complementary to DNAs, but are single-stranded, and consist of chains of the four bases A,G,C and U.

Some segments of DNA code for proteins. These information in these stretches is read by RNA polymerase and transcribed into messenger RNA (mRNA). These mRNAs are then translated into polypeptide chains by ribosomes. These chains then fold into functional proteins.

http://cellbio.utmb.edu/cellbio/DNA-RNA.jpg

Central Dogma

Other segments of DNA code for other RNAs (e.g. ribosomal or rRNAs which form part of the ribosome complex, and transfer or tRNAs which bring amino acids to the ribosome for attachment to the growing polypeptide.)

http://www.designeduniverse.com/articles/Nobel_Prize/trna.jpg

tRNA:

Still other segments of DNA are regulatory regions, whose presence allows the translation of segments of DNA to be influenced by the rest of the cell.

http://www.emc.maricopa.edu/faculty/farabee/BIOBK/repressor_1.gif

The presence of these regulatory elements is central to biological function. Even "simple" organisms exert tight controls over the levels of expressions of most of their proteins. This flexibility allows them to respond to their environment (e.g. to stresses or starvation).

The need for regulation is even more acute in multi-cellular organisms (metazoans). Humans, for instance, have over 200 different cell types. Each has a distinct behaviour, yet all have identical copies of DNA. What distinguishes these types (e.g. muscle from liver) is the profile of proteins which are expressed.

Genes

A gene is a coding region of DNA together with those regulatory elements (called the gene promoter) which influence the rate at which it is translated. The promoter is located "upstream" of the coding region:

simple gene:

promoter start codon coding region stop codon

Regulating molecules (proteins) called transcription factors bind to the regulatory region and either increase the rate of transcription (i.e. upregulate gene expression – a gene activator) or decrease the rate of transcription (i.e. downregulate gene expression – a gene inhibitor).

Simplest cases: typical of prokaryotes

http://www.emc.maricopa.edu/faculty/farabee/BIOBK/repressor_1.gif

Activator binds to regulatory region and recruits RNA polymerase to the promoter (cooperative binding).

Inhibitor binds to regulatory region and blocks RNA polymerase from binding to the gene promoter.

In eukaryotes, regulatory regions are often far-removed from the coding part of the gene, as the DNA is not laid straight.

http://biology.kenyon.edu/courses/biol114/TUTORIAL/gene1-quiz/enhancers.jpg

A genetic regulatory network (or genetic circuit) is a group of genes whose products regulate one another's transcription.

Since each gene can have multiple regulators, expression levels are functions of multiple inputs. (Like allosteric regulation of enzymes and integration of synaptic inputs this feature allows great freedom in network design.)

Genetic networks can be complex...(circadian oscillator)

http://www.molbio.princeton.edu/courses/mb427/2001/projects/03/circadian%20pathway.jpg

or very complex...(brewer's yeast cell cycle)

From Chen, Tyson, Novak Mol. Biol Cell 2000. pp. 369-391

Eric Davidson's Lab at Caltech (http://sugp.caltech.edu/endomes/)

or fantastically complex.

(development of purple sea urchin)

The simplest genetic circuit is an autoregulatory gene (i.e. one whose product regulates its own expression).

• www.accessexcellence.org/ AB/GG/induction.html