Regulation of Gene Expression in Bacteriophages

Bacteriophages or the viruses attacking the bacteria show a specialized mechanism of gene regulation. They follow lytic or lysogenic cycles and reproduce using the bacterial enzymatic machinery. The products of phage genes help in utilizing the essential components provided by the bacterial cells. The phage genes encode for the products essential for the reproduction and growth of the progeny phages. The lambda bacteriophage consists of linear and complementary sticky ends. It circularizes any time. A circular genetic map helps in studying the genes easily. The temperate phages such as lambda phages have a choice between the lytic and the lysogenic pathways.

Image: Regulation of gene expression in bacteriophages

As soon as the phage infects the bacterial cell, its genome gets circularized. The transcription begins at the two promoters P_L and P_R situated at the left and the right respectively. The first gene taken for the transcription process is known as the cro gene. It is present near the P_R promoter. This gene synthesizes a product known as cro protein. It helps the phage in switching over to the lytic cycle. The first gene from the right side taken for the transcription is known as the N gene. This gene encodes a protein known as N protein. It is a transcription anti-terminator. The result of N protein includes the transcription of genes such as cII, O, P, and Q genes respectively. A gene known as cI gene encodes the lambda repressor. This gene gets turned on through cII gene product. The int gene also gets switched on due to the activity of cII protein. This gene encodes for the integrase enzyme. It helps in integrating the lambda chromosome into the host chromosome. The process of integration occurs during the lysogenic pathway. However, the cII protein gets activated only when the phage switches over to the lysogenic pathway. The genes O and P encode two DNA replication proteins. The gene Q encodes proteins required for activating the genes involved in lysis and production of phage proteins. The Q protein also acts as an anti-terminator. It permits the transcription of late genes. 

List of the genes	Product	Their function
PL and PR	-	Early promoters
PR’	-	Late gene promoter
OL and OR	-	Early operators
Cro	Cro protein	Regulator of cI gene
cI	cI	Lambda repressor
cII	cII	Regulator of cI, and int gene expression.
N	N protein	Regulator of early genes
cIII	cIII protein	The stabilizer of cII protein
Bet	Bet protein	Phage recombination protein
Exo	Exo protein	Phage recombination protein
Xis	Excisionase	Excision from the chromosome
Int	Integrase	For integration into the chromosome
Att	-	Attenuation site
J,I,K,L,M,H,T,G,V,U	Tail proteins and assembly proteins	For the bacteriophage tail and assembly
Z, F11, E, D, C, Nu3, B, W, A terminase, and Nu1.	Head proteins and assembly	For head and assembly of the progeny phages
Cos	-	For the lysogenic pathway
Rz, R, and S.	Lysis proteins	Involved in lysis
Q	-	Regulator of late genes
O	Phage DNA replication proteins	DNA replication
P	Phage DNA replication proteins	DNA replication

Table: Bacteriophage genes and their function.

Lysogenic pathway:

The lysogenic pathway involves the role of cII and cIII gene products. The cII protein activates a gene located between the P_L and P_R promoters. The gene is known as the cI gene. The product of the cI gene is known as the lambda repressor. It binds to the operators O_L and O_R situated at the left and the right respectively. The O_L and O_R sequences overlap the promoters P_L and P_R sequences. The binding of the lambda repressor to the operators prevents the transcription of the early operons controlled by the promoters. Hence, it blocks the transcription of genes such as the N and the cro genes. The protein products of the above genes remain in an unstable condition. Hence, their concentrations drop dramatically. The process also involves binding of a repressor to the O_R. It stimulates the synthesis of repressor mRNA. The synthesis involves a different promoter known as P_RM (promoter for repressor maintenance). It helps in maintaining the repressor concentrations in the cell. The establishment of lysogeny requires enough amounts of lambda repressors. These repressors bind to the operators. This step gets followed by the integration of lambda DNA. The step involves the activity of an enzyme known as integrase (the product of promoter P1). Enough synthesis of lambda repressor suffices the lysogenic pathway. It turns off the early promoters involved in regulating the lytic pathway. Hence, the activity of the lambda repressor greatly contributes to the lysogenic pathway and keeping the lytic genes off.

The Lytic Pathway:

The lytic pathway gets induced by the chemical or physical agents such as UV light. It damages the DNA by creating mutations. The protein known as Rec A involves changes in its functioning. This protein plays a crucial role in DNA recombination. During DNA damage such as UV irradiation-induced damage, the Rec A protein stimulates the lambda repressors. The polypeptides of the lambda repressors cleave themselves into two parts upon the action of Rec A. The Rec A protein inactivates them. Since the inactivated repressor does not bind to the operator, the RNA polymerase binds to the P_R. It leads to the transcription of the cro gene. Its product known as cro protein decreases the synthesis of RNA from the P_L and P_R. It also reduces the synthesis of three main components such as cII protein, the lambda repressor protein, and lambda repressor mRNA. It also leads to a significant decrease in the early operon genes from the P_R. The key feature of the regulation involved in lytic cycle involves enough accumulation of Q protein. This protein plays a crucial role in setting the genetic switch for the lytic pathway. It promotes the transcription of the late genes involved in the lytic pathway. 

References:

[1] Introduction to Genetics: A Molecular Approach, Terry Brown

[2] Genomes, T.A Brown

[3] IGenetics, Peter Russell, second edition

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