Gene Expression- Lecture-1

Gene expression is the combined process of the transcription of a gene into mRNA, the processing of that mRNA, and its translation into protein (for protein-encoding genes).

Significance of gene Expression

Regulated expression of genes is required for Adaptation, differentiation, and development,

1) Adaptation

Organisms adapt to environmental changes by altering gene expression.

a) Bacteria are highly versatile and responsive organisms: the rate of synthesis of some proteins in bacteria may vary more than a 1000-fold in response to the supply of nutrients or to environmental challenges. 

b) Cells of multicellular organisms also respond to varying conditions. Such cells exposed to hormones and growth factors change substantially in shape, growth rate, and other characteristics.

2) Tissue-specific differentiation and development

The genetic information present in each somatic cell of a metazoan organism is practically identical. For example, cells from muscle and nerve tissue show strikingly different morphologies and other properties, yet they contain exactly the same DNA. These diverse properties are the result of differences in gene expression.

The exceptions in the genetic information are found in those few cells that have amplified or rearranged genes in order to perform specialized cellular functions.

A comparison of the gene-expression patterns of cells from the pancreas, which secretes digestive enzymes, and the liver, the site of lipid transport and energy transduction, reveals marked differences in the genes that are highly expressed a difference consistent with the physiological roles of these tissues.

Expression of the genetic information must be regulated during ontogeny and differentiation of the organism and its cellular components.

Mammalian cells possess about 1000 times more genetic information than does the bacterium Escherichia coli. Much of this additional genetic information is probably involved in the regulation of gene expression during the differentiation of tissues and biologic processes in the multicellular organism and in ensuring that the organism can respond to complex environmental challenges.

How is gene expression controlled?

Gene activity is controlled first and foremost at the level of transcription. Much of this control is achieved through the interplay between proteins that bind to specific DNA sequences and their DNA binding sites. This can have a positive or negative effect on transcription. Transcription control can result in tissue-specific gene expression.

In addition to transcription level controls, gene expression can also be modulated by gene amplification, gene rearrangement, post-transcriptional modifications, and RNA stabilization. 
Types of gene regulation

There are only two types of gene regulation: positive regulation and negative regulation.

A) Positive regulation
When the expression of genetic information is quantitatively increased by the presence of a specific regulatory element, regulation is said to be positive. The element or molecule mediating positive regulation is a positive regulator or activator.

B) Negative regulation
When the expression of genetic information is diminished by the presence of a specific regulatory element, regulation is said to be negative. The element or molecule mediating negative regulation is said to be a negative regulator or repressor.

A double negative has the effect of acting as a positive. Thus, an effector that inhibits the function of a negative regulator will bring about a positive regulation. Many regulated systems that appear to be induced are in fact derepressed at the molecular level.

Types of responses

The extent or amount of gene expression in response to an inducing signal is observed in three types of temporal responses-

1) Type A response

Type A response is characterized by an increased extent of gene expression that is dependent upon the continued presence of the inducing signal. When the inducing signal is removed, the amount of gene expression diminishes to its basal level, but the amount repeatedly increases in response to the reappearance of the specific signal.

 Examples

This type of response is commonly observed in prokaryotes in response to sudden changes in the intracellular concentration of a nutrient. It is also observed in many higher organisms after exposure to inducers such as hormones, nutrients, or growth factors (figure-1).

2) Type B response

Type B response exhibits an increased amount of gene expression that is transient even in the continued presence of the regulatory signal. After the regulatory signal has terminated and the cell has been allowed to recover, a second transient response to a subsequent regulatory signal may be observed.

Examples

This phenomenon characterizes the action of many pharmacologic agents, but it is also a feature of many naturally occurring processes.

This type of response commonly occurs during the development of an organism, when only the transient appearance of a specific gene product is required although the signal persists.

Figure-1- Showing type-A response. The response is observed only in the presence of a signal.

 Figure-2- showing type B response. The signal persists but the response is transient.

3) Type C response

The type C response pattern exhibits, in response to the regulatory signal, an increased extent of gene expression that persists indefinitely even after termination of the signal. The signal acts as a trigger in this pattern. Once an expression of the gene is initiated in the cell, it cannot be terminated even in the daughter cells; it is, therefore, an irreversible and inherited alteration.

 Example

This type of response typically occurs during the development of differentiated function in a tissue or organ.

 Figure-3- showing type C response. The response is signal independent. Response persists even in the absence of a signal.