The Genetics of
Viruses and Prokaryotes
The Genetics of Viruses and Prokaryotes
• Probing the Nature of Genes
• Viruses: Reproduction and Recombination
• Prokaryotes: Reproduction and Recombination
• Regulation of Gene Expression in Prokaryotes
• Control of Transcription in Viruses
• Prokaryotic Genomes
Probing the Nature of Genes
• Prokaryotes and viruses have advantages for the study of genetics:
§ They have small genomes.
§ They quickly produce large numbers of individuals.
§ They are usually ________ making genetic analyses easier.
Probing the Nature of Genes
• The ease of use of bacteria and viruses in genetic research has propelled the science of genetics and molecular biology during the last 50 years.
• Prokaryotes continue to play a central role as tools for biotechnology and for research on eukaryotes.
• Prokaryotes play important ecological roles, including the cycling of elements.
• Many prokaryotes and viruses are pathogens.
Viruses: Reproduction and Recombination
• Most viruses are composed of a ________ ________ and a few proteins.
• Viruses are________ (noncellular) and do not metabolize energy.
• Viruses do not produce ATP or conduct fermentation, cell respiration, or photosynthesis.
• Viruses can reproduce only in systems that do perform these functions: living cells.
Viruses: Reproduction and Recombination
• The tobacco mosaic virus was the first virus to be discovered in the 1890s, but it was not crystallized until the 1930s.
• In the 1950s, direct observation by electron microscopes showed how much viruses differ from bacteria.
• The simplest ________ agents are viroids, which are made up only of genetic material.

-the following note is not on the slides-if you are reading this carefully, before class, come up to me and if you are the first one to say the phrase that pays “Are prions infectious agents simpler than viroids?"  you will be rewarded.-

Viruses: Reproduction and Recombination
• Viruses are obligate intracellular ________ that develop and reproduce only within living cells of specific hosts.
• Viruses reproduce using the host's synthetic machinery and usually destroy the host cell in the process.
• The host cell releases progeny viruses, which then infect new hosts.
• Outside the cell, the individual viral particles are called virions.
Viruses: Reproduction and Recombination
• Virion genetic material is either DNA or RNA and is generally surrounded by a capsid, or protein coat.
• Characteristic shapes are determined by the protein coat.
• Viruses are unaffected by antibiotics because they lack the cell wall structure and ribosomal biochemistry of bacteria.

Viruses: Reproduction and Recombination
• Viruses are described according to four different criteria:
§ Whether the genome is DNA or RNA
§ Whether the nucleic acid is single-stranded or double-stranded
§ Whether the shape of the virion is a simple or complex crystal
§ Whether or not the virion is surrounded by a membrane
Viruses: Reproduction and Recombination
• Viruses that infect bacteria are called bacteriophage.
• ________ recognize their host by means of specific binding between proteins in the capsid and receptor proteins on the host's cell.
• The virions are equipped with tail assemblies that inject the phage's nucleic acid into the host cell.
Viruses: Reproduction and Recombination
• The virus may reproduce immediately and kill the host, or postpone reproduction by integrating its nucleic acid into the host's genome.
• There are two types of reproductive cycles: the lytic cycle and the lysogenic cycle.
Viruses: Reproduction and Recombination
• In the lytic cycle, the infected bacterium lyses, releasing the progeny phage.
• Phage that only have lytic cycles are called virulent viruses.
• The phage nucleic acid takes over the host's synthetic machinery in two stages: early and late stage.
Viruses: Reproduction and Recombination
• The viral genome contains a promoter sequence that attracts host RNA polymerase.
• In the early stage, viral genes adjacent to the promoter are transcribed. Early gene products often include proteins that shut down host transcription and stimulate viral genome replication.
• In the late stage, viral late genes code for the protein coat and an enzyme that causes host cell lysis, resulting in viral release.
Viruses: Reproduction and Recombination
• In the lysogenic cycle, the host cell does not lyse, but harbors the viral nucleic acid for many generations.
• Bacteria harboring phage that are not lytic are called lysogenic bacteria.
• The viruses are called ________ viruses.
Viruses: Reproduction and Recombination
• Lysogenic bacteria have a molecule of noninfective phage DNA called a prophage inserted into their chromosome.
• Under some conditions, the prophage replicates during the bacterium's normal reproductive cycle without otherwise harming the bacterium.
• Certain conditions will activate the prophage, initiating a lytic cycle that results in the release of a large number of free phage.


Viruses: Reproduction and Recombination
• Lytic bacteriophage destroy their bacterial hosts, and thus might be useful in treating diseases caused by bacteria.
• Early work by D'Herelle showed that phage could be used to control some bacterial diseases.
• Rise of antibiotics reduced interest in phage therapy, but it may become useful again, as bacteria become resistant to antibiotics.
Viruses: Reproduction and Recombination
• Animal viruses are diverse.
• Arboviruses infect both insects and vertebrates. The virus passes from arthropod to vertebrate via an insect bite. The arthropod is a vector (carrier).
• Animal viruses include those that are just particles of protein surrounding a nucleic acid core as well as those that have a membrane derived from that of the host.
• Some animal viruses have DNA, and some have RNA, but all have small genomes.
Viruses: Reproduction and Recombination
• Animal viruses enter cells in three different ways:
§ Endocytosis of a naked virion
§ Endocytosis of a membrane-encased virus
§ Fusion of a membrane-encased virus with the cell's membrane
• The life cycles of influenza virus and HIV illustrate two styles of infection and reproduction.

Viruses: Reproduction and Recombination
• Plant viruses can be transmitted in two ways:
§ Horizontal transmission is the spread of viruses from one plant to another.
§ Vertical transmission is the transfer of viruses from parent plant to offspring.
Viruses: Reproduction and Recombination
• To infect a plant cell, the virus must penetrate a ________ ________ and ________________ • Insects are possible vectors. A virion-laden insect feeding on a plant can penetrate the cell wall and insert the virus.
• Another means of infection is contact between damaged tissue of an infected and a noninfected plant.
Viruses: Reproduction and Recombination
• Vertical transmission can occur through vegetative or sexual reproduction.
• Once inside a plant cell, viruses can spread by moving through plasmodesmata, the cytoplasmic connections between cells.
• The viruses bind with special proteins that assist their travel through the otherwise too narrow plasmodesmata pores.
Prokaryotes: Reproduction and Recombination
• Unlike viruses, bacteria and archaea are living cells that carry out basic cellular functions.
• The division of single cells into two identical offspring produces clones, or genetically identical individuals.
• If a number of cells are spread on a semisolid medium containing agar, individual cells give rise to clearly visible colonies.

Prokaryotes: Reproduction and Recombination
• In 1946, Lederberg and Tatum demonstrated the exchange of DNA between two living bacteria.
• This exchange is called________
• The physical contact required for conjugation is initiated by a ________ which is a fine projection produced by the donor cell.
• The DNA transfers through a thin cytoplasmic bridge called a conjugation tube.
• Once the DNA fragment is inside the recipient cell, it recombines with homologous genes.


Prokaryotes: Reproduction and Recombination
• Transformation of bacteria occurs when bacteria take up extracellular DNA and incorporate it.
• More than 75 years ago, Frederick Griffith obtained the first evidence for transfer of genes between bacteria.
Prokaryotes: Reproduction and Recombination
• In ________ viruses carry genes from one cell to another
• During the lytic cycle, some bacteriophage package a host bacterium's DNA in capsids, or viral protein coats.
• Cells infected by such viruses get a segment of another bacterium's DNA, not the viral DNA.
• In transduction, this bacterial DNA recombines with the chromosomal DNA of the host and alters its genetic composition.

Prokaryotes: Reproduction and Recombination
• Plasmids are small, circular chromosomes found in many bacteria.
• Each plasmid replicates separately from the primary chromosome.
• Plasmids move between bacterial cells during conjugation.
• Different types of plasmids are classified according to the kinds of genes they carry.
• Some plasmids (metabolic factors) carry genes for unusual metabolic functions, such as degrading oils from oil spills.
Prokaryotes: Reproduction and Recombination
• Fertility factors (F factors) are plasmids that carry genes for conjugation.
• Around 25 genes, including the ones responsible for the pilus, are on the F factor plasmid.
• Bacteria with this plasmid are called F+.
• On occasion, this F plasmid inserts into the main chromosome.
• When this occurs, chromosomal genes can be transferred during conjugation.

Prokaryotes: Reproduction and Recombination
• Some plasmids are resistance factors (R factors) and carry genes that code for proteins that protect the bacteria.
• Antibiotic resistance genes interfere with antibiotic activity or transport.
• Research found that resistance to an entire spectrum of antibiotics could be transferred by conjugation.
• This finding raised the warning that inappropriate use of antibiotics may lead to their becoming ineffective.
Prokaryotes: Reproduction and Recombination
• Segments of chromosomes or plastids that can move into other genes within a cell are called transposable elements.
• The movement of these t________ elements into other genes disrupts normal function.
• Long transposable elements (about 5000 base pairs), which include one or more genes, are called transposons.
• Transposons have contributed to the evolution of plasmids, and there is some evidence that R factors developed antibiotic resistance through transposons.

Regulation of Gene Expression in Prokaryotes
• Prokaryotes can conserve energy and resources by making proteins only when they are needed.
• Cells can regulate protein synthesis by several methods:
§ Block transcription of the gene that codes for a protein
§ Hydrolyze the mRNA after it is made
§ Prevent translation of mRNA at the ribosome
§ Hydrolyze the protein after it is made
§ Inhibit the function of the protein
Regulation of Gene Expression in Prokaryotes
• E. coli prefers glucose as an energy source, but can use lactose if glucose is low.
• Three enzymes are required for lactose metabolism.
• Presence of lactose stimulates production of these enzymes. Lactose is an________
• The enzymes that are produced are said to be inducible.
• Enzymes that are made all the time are said to be constitutive.
Regulation of Gene Expression in Prokaryotes
• There are two basic ways of regulating the rate of a metabolic pathway:
§ Allosteric regulation
§ Regulation of protein synthesis

Regulation of Gene Expression in Prokaryotes
• Structural genes specify the primary structures (amino acid sequence) of a protein molecule.
• The three structural genes involved in lactose metabolism are adjacent to each other on the E. coli chromosome.
• All are ________ together when a single promoter binds RNA polymerase.
• When these enzymes are not needed, the mRNA synthesis must be shut down, using the operon mechanism.
Regulation of Gene Expression in Prokaryotes
• Prokaryotes shut down transcription by placing an obstacle between the promoter and its structural genes, called the operator.
• If a specific protein, the repressor, binds to the operator, it creates an obstacle, and RNA polymerase is blocked from transcribing the structural genes.
• When the repressor is not attached to the operator, mRNA synthesis proceeds.
• The whole unit of genes and their DNA controls is called an operon.

Regulation of Gene Expression in Prokaryotes
• The ________ for the three lactose-metabolizing enzymes is called the lac operon.
• The repressor protein has two binding sites: one for the operator and the other for inducers.
• Binding of the repressor by the inducer molecules (lactose) changes the shape of the repressor by allosteric modification.
• The change in shape prevents the repressor from binding to the operator.
• Thus, RNA polymerase can bind to the promoter and start gene transcription of the lac operon.
Regulation of Gene Expression in Prokaryotes
• If the concentration of the inducer (lactose) drops, the functioning repressor binds the operator, and the enzymes for lactose metabolism are not synthesized.
• If the concentration of lactose rises, the repressor itself is bound and does not bind the operator. The enzymes for lactose metabolism are synthesized.


Regulation of Gene Expression in Prokaryotes
• The repressor protein is coded for by the regulatory gene.
• The regulatory gene that codes for the lac repressor is the i (inducibility) gene.
• The i gene is located near the lac structural genes. However, not all regulatory genes are near the operons they control.
• Regulatory genes like i have their own promoter, called pi.
• The i gene is expressed constitutively (expression is constant).

Regulation of Gene Expression in Prokaryotes
• Summary of the lac operon control:
§ When no inducer (lactose) is present, lac is off.
§ The regulator protein (repressor) turns the operon off.
§ The i gene produces the repressor.
§ The operator and promoter are DNA sequences that are binding sites for regulatory proteins.
§ Adding inducer (lactose) turns the operon on.
Regulation of Gene Expression in Prokaryotes
• If synthesis of an enzyme can be turned off, it is said to be________
• The trp operon in E. coli is repressible.
• In the absence of tryptophan, RNA polymerase transcribes the trp operon, leading to production of enzymes that synthesize tryptophan.
• When tryptophan is present, it binds to a repressor, which becomes active.
• The repressor binds to the operator of the trp operon, blocking production of enzymes for tryptophan synthesis.




Regulation of Gene Expression in Prokaryotes
• The molecule that binds and activates a repressor is called a corepressor.
• The corepressor may be the end product of the operon (as in the case of tryptophan), or an analog.
• In inducible systems, an inducer from the cell's environment prevents a repressor from blocking transcription.
• In repressible systems, a corepressor produced by the cell activates a repressor, enabling it to block transcription.
Regulation of Gene Expression in Prokaryotes
• Another way to regulate transcription is to make the promoter sequence of the operon work more efficiently.
• When glucose is high, even when lactose is available, the lac operon fails to transcribe frequently.
• When glucose is low, and lactose is available, lac structural genes are transcribed.
• Low glucose levels cause elevated levels of cyclic AMP (cAMP).
Regulation of Gene Expression in Prokaryotes
• When glucose is low and cAMP is high, cAMP binds to a protein called CRP.
• The CRP–cAMP complex binds the DNA just upstream of the promoter.
• Binding of this site makes it easier for RNA polymerase to bind the promoter and thus increases rates of transcription.



Regulation of Gene Expression in Prokaryotes
• When glucose is abundant, cAMP levels drop.
• The CRP–cAMP complex does not form.
• Without the CRP–cAMP complex, RNA polymerase cannot bind to the promoter efficiently.
• The lac structural genes are not transcribed.
• This is called catabolite repression.
Control of Transcription in Viruses
• Viruses also have gene regulation mechanisms.
• Bacteriophage l is a temperate phage, meaning that it can undergo either a lytic or a lysogenic cycle.
• When host bacteria are growing in rich medium, the prophage remains lysogenic; when the host is less healthy, the prophage becomes lytic.
• A "genetic switch" determines the prophage behavior.
Control of Transcription in Viruses
• Two regulatory proteins, cI and Cro, compete for two operator/promoter sites on phage DNA.
• One operator controls the lytic gene activities; the other, lysogenic cycles.
• The two regulatory proteins have opposite effects on the two operators.
• cI represses the lytic operator/promoter and activates the lysogenic operator/promoter.
• Cro activates the lytic operator/promoter and represses the lysogenic operator/promoter.
• The relative concentrations of cI and Cro determine the outcome.

Prokaryotic Genomes
• Viral genomes were the first to be sequenced.
• Three types of information can be obtained from a genomic sequence:
§ Open reading frames can be recognized by promoter regions and start and stop codons.
§ Amino acid sequences can be deduced from the DNA sequence.
§ Gene control sequences of promoters and terminators can be identified.
Prokaryotic Genomes
• Functional genomics is the assignment of roles to the products of genes described by genomic sequencing.
• Haemophilus influenzae has a circular chromosome of 1,830,137 base pairs and 1,743 protein-coding regions.
• When it was sequenced, 42 percent of the genes coded for proteins with unknown functions.
• Roles for most of the unknown proteins have now been identified by a process known as annotation.

Prokaryotic Genomes
• Comparative genomics involves the comparison of genome sequences of different organisms.
• In addition to the sequences for H. influenzae, those for Mycoplasma genitalium (580,070 base pairs) and E. coli (4,639,211 base pairs) have been completed.
Prokaryotic Genomes
• Scientists are discovering genes for proteins in prokaryotes that cause infectious diseases.
• These are potential targets for new drugs.
• New vaccines may be possible as cell surface antigen coding genes are discovered.
Prokaryotic Genomes
• There are some universal genes needed by all organisms, such as those coding for an ATP binding site.
• M. genitalium has just 470 genes, the smallest known genome.
• Using mutagens to knock out genes, scientists have determined that M. genitalium can survive in the laboratory with just ________ genes.
• This number is termed the "minimal essential genome."

Animation 13.1 The lac Operon
Animation 13.2 The trp Operon
Video 13-01