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The Classical Genetic Switch in Lambda
Phage- Lysis and Lysogeny decisions
Dr. M. Vijayalakshmi
School of Chemical and Biotechnology
SASTRA University
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Table of Contents
1 LYSIS VERSUS LYSOGENY ........................................................................... 3
1.1 LYSIS ........................................................................................................... 3
1.2 FUNCTION OF THE SWITCH IN LAMBDA PHAGE ................................................... 5
1.3 LYSOGENEIC STATE ........................................................................................ 6
2 REFERENCES .................................................................................................. 8
2.1 TEXT BOOK ................................................................................................... 8
2.2 LITERATURE REFERENCES ............................................................................. 8
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1 Lysis versus Lysogeny
1.1 Lysis
The lysis-lysogeny decision of the temperate lambda phage has emerged as a
novel paradigm for understanding developmental genetic networks. E.coli and
the lambda phage establish synergistic relationships. The lambda phage may
exist in a dormant lysogenic state, passively replicating with the host
chromosome or may fall into the lytic cycle generating progeny phages, killing
their hosts. The lambda phage therefore makes a decision to follow either the
lytic or the lysogenic pathway.
When the lambda phage follows the lytic pathway, it replicates its DNA
autonomously, expresses a set of genes, and assembles the virions, resulting in
lysis of the host. If the lysogenic state continues over a long time, a stable
lysogen is established in the circuit and the prophage is integrated to the host
genome. This turns OFF the expression of the lytic genes.
Inducing signals like UV light that damage the DNA, force the lambda phage to a
SOS response and the lysogenic state switches irreversibly to the lytic phase as
shown in Fig 1. The lambda phage thus behaves as a biphasic switch.
Fig 1. Growth and induction of the Lambda lysogen
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The genetic map of the lambda phage is shown in Fig 2.
Fig 2. Genetic map of the lambda phage
The gene arrangement and sites involved in switching are shown in Fig 3 and 4.
Fig 3. The biphasic switch
Fig 4. Arrangement of genes and sites of OR
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1.2 Function of the switch in Lambda phage
In order to understand how switching happens between the lysis and lysogeny
states in the lambda phage, we focus on two regulatory genes CI and cro and a
regulatory region OR called the right operator as shown in Fig 3. During the
lysogeny phase CI is switched ON and cro is OFF. The operator OR is constituted
of three binding sites ORI, ORII and ORIII which overlap two promoters PRM and PR
which oppose each other as shown in Fig 4. The promoter PR drives the
transcription of lytic genes and PRM, the transcription of the CI gene. During the
lysogenic state, the lambda repressor at OR is bound at ORI and ORII, sites
adjacent to each other. At these sites, the repressor represses the right ward
transcription from the promoter PR. the expression of cro and other lytic genes is
therefore turned OFF. At the same time, it also transcribes its own gene from the
promoter PRM as shown in Fig 5. When induced, the repressor leaves the
operator and transcription from PR is initiated spontaneously. Please note that PR
is a stronger promoter than PRM. As transcription begins, the CRO protein is
made which binds first to ORIII abolishing the synthesis of the repressor.
Fig 5. Role of Lambda repressor and cro
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1.3 Lysogeneic state
We know that the lambda repressor is required to regulate the transcription of its
own gene. We then question how this gene is switched ON to establish lysogeny
during the viral infection. The repressor is transcribed initially from the promoter
PRE (Promoter for repressor establishment) as shown in Fig 6. This transcription
is activated by CII, a product of another phage gene. Thus, a new repressor CI is
made and it activates its own transcription from PRM. This switches OFF the other
phage genes including CII. Thus we see the establishment of lysogeny in lambda
phage, even in the absence of the inducer signal.
Fig 6. Establishment of lysogeny
The life styles of the phage lambda present a classic case of complex genetic
control circuits. It is interesting to understand a small set of regulatory proteins
yielding a complex set of temporally controlled macro molecular interactions in a
simple organism like the lambda phage. Systems biology approaches will help
understand the function of specific modules of these regulatory domains and will
help understand the kinetic behavior and quantitative picture of the genetic circuit
of the lambda phage.
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Video – The Lytic and lysogeny states of lambda phage
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2 References
2.1 Text book
1. A Genetic switch: Phage lambda revisited 2004, 3/e, CSHL Press, New
York.
2.2 Literature References
1. Amos B. Oppenheim, Oren Kobiler, Joel Stavans, Donald L. Court, and
Sankar Adhya, Switches in bacteriophage lamda development, Annu.
Rev. Genet. (2005), 39, 409-429.
2. Atsumi S, Little J W, regulatory circuit design and evolution using lambda
pahge, Genes Dev., (2004), 18, 2086-2094.
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