Gene Regulation In 1961, Francois Jacob and Jacques Monod proposed the operon model for the control of gene expression in bacteria. An operon consists of three elements: the genes that it controls, In bacteria, the genes coding for a protein are transcribed (or not) as one long mRNA molecule. a promoter region where RNA polymerase first binds, an operator region between the promoter and the first gene which acts as an “on-off switch”. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

By itself, an operon is always avaliable for transcription and RNA polymerase can bind to the promoter and transcribe the genes. Fig. 18.20a Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

However, if a repressor protein, a product of a regulatory gene, binds to the operator, it can prevent transcription of the operon’s genes. Each repressor protein recognizes and binds only to the operator of a certain operon. Regulatory genes are transcribed at low rates continuously. Fig. 18.20b Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

The lac operon, containing a series of genes that code for enzymes, which play a major role is the hydrolysis and metabolism for lactose. In the absence of lactose, this operon is off as an active repressor binds to the operator and prevents transcription. Fig. 18.21a Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

When lactose is present in the cell, allolactase, an isomer of lactose, binds to the repressor. This inactivates the repressor, and the lac operon can be transcribed (is turned on). Fig. 18.21b Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Both repressible and inducible operons demonstrate negative control because active repressors can only have negative effects on transcription. Positive gene control occurs when an activator molecule interacts directly with the genome to switch transcription on or enhance transcription.

Eukaryotic cells modify RNA after transcription Enzymes in the eukaryotic nucleus modify mRNA before the genetic messages are dispatched to the cytoplasm. Following transcription, at the 5’ end of the mRNA molecule, a modified form of guanine is added, the 5’ cap and a poly-A tail. These helps protect mRNA from hydrolytic enzymes. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Eukaryotic genes contain parts of the nucleotide sequence that is transcribed and then removed before translation. Exons are spliced together to form the final mRNA that is translated. Introns are the sequences removed before translation

RNA Processing

Fig. 17.9 RNA splicing removes introns and joins exons to create an mRNA molecule with a continuous coding sequence. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

RNA splicing appears to have several functions. First, at least some introns contain sequences that control gene activity in some way. Splicing itself may regulate the passage of mRNA from the nucleus to the cytoplasm. One clear benefit of split genes is to enable a one gene to encode for more than one polypeptide. Alternative RNA splicing gives rise to two or more different polypeptides, depending on which segments are treated as exons. Results of the Human Genome Project indicate that this phenomenon is common in humans. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Split genes may also facilitate the evolution of new proteins. Proteins often have a modular architecture with discrete structural and functional regions called domains. In many cases, different exons code for different domains of a protein. Fig. 17.11 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Point mutations can affect protein structure and function Mutations are changes in the genetic material of a cell (or virus). These include large-scale mutations in which long segments of DNA are affected (for example, translocations, duplications, and inversions). A chemical change in just one base pair of a gene causes a point mutation. If these occur in gametes or cells producing gametes, they may be transmitted to future generations.

Substitution: For example, sickle-cell disease is caused by a mutation of a single base pair in the gene that codes for one of the polypeptides of hemoglobin. A change in a T to A (substitution) in the DNA template leads to an abnormal protein. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 17.23

Missense Mutation

Nonsense Mutation

Frameshift Mutations: Insertion and Deletion Point Mutations Insertion: A single nucleotide base is inserted into a DNA sequence. Deletion: A single nucleotide is removed to a DNA sequence. How the ribosome reads the nucleotide codons changes ie. it changes the reading frame.

Deletion Insertion Fig. 17.24 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings