Chapter 18Chapter 18

The Genetics of Viruses The Genetics of Viruses and Bacteriaand Bacteria

VirusesViruses► A Virus is an infectious particle A Virus is an infectious particle

consisting of a genome consisting of a genome enclosed in a protein coat that enclosed in a protein coat that can only reproduce within a can only reproduce within a host cell. Contains no host cell. Contains no metabolic enzymes, no metabolic enzymes, no ribosomes, etc.ribosomes, etc.

StructureStructure► Viral genome can consist of double or Viral genome can consist of double or

single stranded _single stranded _DNADNA_ or __ or _RNA_RNA_ organized as single molecule (either linear organized as single molecule (either linear or circular).or circular).

VirusesViruses

► The protein coat enclosing the virus is The protein coat enclosing the virus is called a CAPSID.called a CAPSID.

► Some viruses have ENVELOPES Some viruses have ENVELOPES (derived the membranes of host cells) (derived the membranes of host cells) that surround their capsids.that surround their capsids.

► The most complex capsids are found The most complex capsids are found in viruses that infect bacteria known in viruses that infect bacteria known as BACTERIOPHAGES or just PHAGES.as BACTERIOPHAGES or just PHAGES.

VirusesViruses

-Each type of virus can infect a -Each type of virus can infect a limited number of hosts and limited number of hosts and some are species specific. some are species specific.

Viruses are only able to Viruses are only able to reproduce reproduce in a host cell, in a host cell, using the host cell’s using the host cell’s enzymes, enzymes, nucleotides, molecules, nucleotides, molecules, etc etc to copy its own genome and to copy its own genome and make its own proteins.make its own proteins.

VirusesViruses

Viruses that infect bacteria are some of Viruses that infect bacteria are some of the most well understood viruses. Any the most well understood viruses. Any virus, that infects a bacterium is called virus, that infects a bacterium is called a bacteriophage or just phage for short.a bacteriophage or just phage for short.

We will take a look at their reproductive We will take a look at their reproductive cycles (these cycles & variations on cycles (these cycles & variations on them are also common in viruses that them are also common in viruses that infect animals & plants)infect animals & plants)

Common Reproductive Common Reproductive Cycles (of Phages)Cycles (of Phages)

The Lytic Cycle: The Lytic Cycle: results in the death results in the death of the host cell.of the host cell.

Phage that reproduces only Phage that reproduces only using this using this cycle is called a cycle is called a virulentvirulent phage. phage.

Common Reproductive Common Reproductive Cycles (of Phages)Cycles (of Phages)

► Basic steps of lytic cycle:Basic steps of lytic cycle: Phage attaches to host bacteria cell.Phage attaches to host bacteria cell. Phage injects its GENOME into host cell.Phage injects its GENOME into host cell. Phage DNA is copied and phage proteins Phage DNA is copied and phage proteins

are made by the host cell’s “machinery” are made by the host cell’s “machinery” (enzymes, etc)(enzymes, etc)

Common Reproductive Common Reproductive Cycles (of Phages)Cycles (of Phages)

Phage proteins and nucleic acids self Phage proteins and nucleic acids self assemble into genome with capsid assemble into genome with capsid around it.around it.

Phage produces an enzyme that breaks Phage produces an enzyme that breaks the bacterial cell wall, killing it and the bacterial cell wall, killing it and releasing all the newly formed phages. releasing all the newly formed phages.

Bacteria can defend against viral Bacteria can defend against viral (phage) infections by using RESTRICTION (phage) infections by using RESTRICTION enzymes that recognize and cut up enzymes that recognize and cut up foreign DNA.foreign DNA.

Common ReproductiveCommon Reproductive Cycles Cycles (of Phages)(of Phages)

► The Lysogenic Cycle: The Lysogenic Cycle: replicates replicates the phage genome without the phage genome without destroying the host.destroying the host.

Phages that use this and Phages that use this and lytic lytic cycle are called cycle are called temperate temperate phages. phages.

Common Reproductive Common Reproductive Cycles (of Phages)Cycles (of Phages)

► Basics of lysogenic cycle:Basics of lysogenic cycle: Again, phage injects its DNA/RNA into Again, phage injects its DNA/RNA into

host cell.host cell. This time, phage DNA is incorporated This time, phage DNA is incorporated

into the host cell’s genome. When this into the host cell’s genome. When this happens, the viral DNA is called a happens, the viral DNA is called a PROPHAGE. PROPHAGE.

Every time the host cell REPLICATES its Every time the host cell REPLICATES its DNA, it also copies the phage DNA. DNA, it also copies the phage DNA. This enables the virus to spread without This enables the virus to spread without killing its host cells.killing its host cells.

Common Reproductive Common Reproductive Cycles (of Phages)Cycles (of Phages)

Eventually, an environmental or chemical Eventually, an environmental or chemical signal triggers the phage DNA to exit the signal triggers the phage DNA to exit the host’s genome and initiate a LYTIC cycle.host’s genome and initiate a LYTIC cycle.

Additional information: the presence of Additional information: the presence of phage DNA in other wise harmless phage DNA in other wise harmless bacteria can be BAD. Expression of bacteria can be BAD. Expression of prophage DNA can alter the host prophage DNA can alter the host bacteria’s phenotype and trigger it to bacteria’s phenotype and trigger it to make toxins which are harmful to humans make toxins which are harmful to humans (this is how diphtheria, botulism and (this is how diphtheria, botulism and scarlet fever are caused).scarlet fever are caused).

Viruses that Infect Viruses that Infect AnimalsAnimals

Structure: almost all animal viruses Structure: almost all animal viruses are equipped with outer are equipped with outer envelopes that are derived from envelopes that are derived from the host’s plasma membrane.the host’s plasma membrane.

After the virus’ genome & capsid proteins are After the virus’ genome & capsid proteins are made, the virus “buds” from the host cell made, the virus “buds” from the host cell plasma membrane – which doesn’t plasma membrane – which doesn’t necessarily kill the host cell.necessarily kill the host cell.

Viruses that Infect AnimalsViruses that Infect Animals

Many animal viruses have RNA as genetic material. Many animal viruses have RNA as genetic material. There are differences in how the RNA is translated There are differences in how the RNA is translated into viral proteinsinto viral proteins

► Some RNA serves directly as mRNA and can Some RNA serves directly as mRNA and can immediately be translated into viral proteins immediately be translated into viral proteins upon entering the host.upon entering the host.

► Some RNA serves as a template for Some RNA serves as a template for transcription and a complementary mRNA transcription and a complementary mRNA strand is made (then translation proceeds).strand is made (then translation proceeds).

► RETROVIRUSES: transcribe DNA from an RNA RETROVIRUSES: transcribe DNA from an RNA template using an enzyme called REVERSE template using an enzyme called REVERSE TRANSCRIPTASE.TRANSCRIPTASE.

The newly made DNA then integrates as a The newly made DNA then integrates as a provirusprovirus into a chromosome within the into a chromosome within the nucleus of the host cellnucleus of the host cell. .

Viruses that Infect AnimalsViruses that Infect Animals

Then, the host transcribes and translates Then, the host transcribes and translates the viral DNA into viral proteins. the viral DNA into viral proteins.

HIV is a retrovirus.HIV is a retrovirus. ALL RNA viruses have a high mutation ALL RNA viruses have a high mutation

rate because there is no proofreading rate because there is no proofreading mechanism. This is why you can ALWAYS mechanism. This is why you can ALWAYS get a cold or flu --- there are always new get a cold or flu --- there are always new strains. This also means that viruses like strains. This also means that viruses like HIV are constantly mutating.HIV are constantly mutating.

Evolution of Viruses Evolution of Viruses

►1.) Can they evolve? Are they alive? 1.) Can they evolve? Are they alive? Well, they do change based on their Well, they do change based on their genetic code – which they share with all genetic code – which they share with all other living organisms.other living organisms.

►2.) Most likely evolved AFTER cells 2.) Most likely evolved AFTER cells since they are so dependent on them.since they are so dependent on them.

►a.) Hypothesis: viruses originated from a.) Hypothesis: viruses originated from pieces of cellular nucleic acids that pieces of cellular nucleic acids that could move from one cell to another.could move from one cell to another.

Viral Diseases Viral Diseases

Viruses cause disease by lysing cells, causing Viruses cause disease by lysing cells, causing infected cells to produce toxins or having infected cells to produce toxins or having components that are toxic (proteins in viral components that are toxic (proteins in viral envelopes).envelopes).

The symptoms we get from the most The symptoms we get from the most common viral infections are usually common viral infections are usually from our own body’s defenses.from our own body’s defenses.

The permanent damage inflicted by a The permanent damage inflicted by a virus usually depends on what type of virus usually depends on what type of cells it infects and how well they can cells it infects and how well they can repair themselves.repair themselves.

Viral DiseasesViral Diseases

► Treating viruses is HARD. Antibiotics Treating viruses is HARD. Antibiotics kill bacteria because they destroy kill bacteria because they destroy bacterial proteins/enzymes. Viruses bacterial proteins/enzymes. Viruses do not have many enzymes of their do not have many enzymes of their own and it is hard to develop antiviral own and it is hard to develop antiviral drugs. drugs.

► a.) Most antiviral drugs are designed to a.) Most antiviral drugs are designed to interfere with the synthesis of the virus’ interfere with the synthesis of the virus’ genetic material.genetic material.

Viroids + Prions = WEIRD!Viroids + Prions = WEIRD! Viroids: Viroids: naked, circular RNA that naked, circular RNA that

infects plants (so this is an infects plants (so this is an infectious infectious moleculemolecule).).

RNA replicates in host cells RNA replicates in host cells using their using their enzymes and disrupts enzymes and disrupts plant cell plant cell metabolism, stunting plant metabolism, stunting plant growthgrowth. .

►

Prions: Prions: infectious proteinsinfectious proteins Leading Hypothesis: prions are misfolded forms Leading Hypothesis: prions are misfolded forms

of proteins that are normally present in brain of proteins that are normally present in brain cells and once inside brain cells can actually cells and once inside brain cells can actually convert the normal proteins into the misfolded convert the normal proteins into the misfolded form. form.

This damages/destroys brain cells.This damages/destroys brain cells. Example: Mad Cow DiseaseExample: Mad Cow Disease

The Genetics of BacteriaThe Genetics of Bacteria

► most bacteria have one, circular most bacteria have one, circular chromosome composed of chromosome composed of double stranded DNA.double stranded DNA.

The Genetics of BacteriaThe Genetics of Bacteria

In addition to chromosome, many In addition to chromosome, many bacteria also have smaller, self – bacteria also have smaller, self – replicating circles of DNA in the replicating circles of DNA in the cytoplasm called PLASMIDS.cytoplasm called PLASMIDS.

Bacteria reproduce by replicating their Bacteria reproduce by replicating their chromosome and dividing by BINARY chromosome and dividing by BINARY FISSION. FISSION.

Since this is an asexual process, most Since this is an asexual process, most bacteria in a colony are genetically bacteria in a colony are genetically identical. However, mutations and identical. However, mutations and recombination are possible:recombination are possible:

TRANSFORMATION: The uptake of TRANSFORMATION: The uptake of naked, foreign DNA from the naked, foreign DNA from the environment which is then incorporated environment which is then incorporated into the bacterial chromosome.into the bacterial chromosome.

► TRANSDUCTION: phages carry TRANSDUCTION: phages carry bacterial genes from one host cell to bacterial genes from one host cell to another (so a virus does the dirty another (so a virus does the dirty work of transferring DNA). This can work of transferring DNA). This can happen by chance packaging of happen by chance packaging of host’s DNA into a viral capsid or host’s DNA into a viral capsid or when a prophage leaves a host’s when a prophage leaves a host’s genome it may take a piece of the genome it may take a piece of the host’s DNA with it. host’s DNA with it.

► Bacteia sex! Also known as Bacteia sex! Also known as CONJUGATION: the direct transfer of CONJUGATION: the direct transfer of genetic material between temporarily genetic material between temporarily joined bacteria. joined bacteria.

► One cell donates DNA and extends a SEX PILUS One cell donates DNA and extends a SEX PILUS (OH MY!) which joins to a recipient cell and DNA is (OH MY!) which joins to a recipient cell and DNA is transferred from donor to recipient.transferred from donor to recipient.

► The ability to grow a sex pilus and transfer DNA is The ability to grow a sex pilus and transfer DNA is determined by the presence of a piece of DNA determined by the presence of a piece of DNA known as the F factor. known as the F factor.

► This factor can be part of the bacterial This factor can be part of the bacterial chromosome or can be part of plasmid (the F chromosome or can be part of plasmid (the F plasmid) in the bacteria. plasmid) in the bacteria.

A single strand of the F plasmid is transferred and is used as a template in both the donor and recipient cells to make the complementary DNA strand.

PlasmidsPlasmids

► generally beneficial to bacteria, not generally beneficial to bacteria, not required for survival of bacteria under required for survival of bacteria under normal conditions, can be transferred normal conditions, can be transferred from one bacteria to another (through from one bacteria to another (through conjugation, transformation), are self conjugation, transformation), are self replicating (so when a bacterium replicating (so when a bacterium divides, its plasmid has usually divides, its plasmid has usually replicated and is passed to the two replicated and is passed to the two resulting daughter cells).resulting daughter cells).

R plasmids: contain genes that R plasmids: contain genes that make bacteria resistant to make bacteria resistant to antibiotics.antibiotics.

Many of these also have genes encoding Many of these also have genes encoding for sex pili so they are transferred for sex pili so they are transferred between bacteria.between bacteria.

► Some contain genes that make them Some contain genes that make them resistant to many antibiotics. resistant to many antibiotics.

This is most likely the result of genes This is most likely the result of genes that can actually move from one location that can actually move from one location to another in a genome (in a single cell) to another in a genome (in a single cell) – called TRANSPOSONS.– called TRANSPOSONS.

These genes can move within a bacterial These genes can move within a bacterial chromosome, between the chromosome chromosome, between the chromosome and plasmid or from one plasmid to and plasmid or from one plasmid to another.another.

Simplest type of transposons are called Simplest type of transposons are called

INSERTION sequences. They code for INSERTION sequences. They code for only one enzyme, TRANSPOSASE which only one enzyme, TRANSPOSASE which is the enzyme that catalyzes their is the enzyme that catalyzes their movement. When these are inserted movement. When these are inserted into other regions of coding DNA, they into other regions of coding DNA, they can cause mutationscan cause mutations

Other transposons have more than one Other transposons have more than one gene (maybe genes for antibiotic gene (maybe genes for antibiotic resistance). So when these are inserted resistance). So when these are inserted into plasmids or bacterial into plasmids or bacterial chromosomes, you can end up with chromosomes, you can end up with bacteria that is resistant to multiple bacteria that is resistant to multiple antibiotics.antibiotics.

Eukaryotes also have mobile genetic Eukaryotes also have mobile genetic elements like transposons!elements like transposons!

Bacterial Control of Gene Bacterial Control of Gene ExpressionExpression

► The Operon ModelThe Operon Model Genes that code for proteins/enzymes Genes that code for proteins/enzymes

that are functionally related are all that are functionally related are all grouped together in the genome grouped together in the genome (forming one big transcription unit) and (forming one big transcription unit) and have a single PROMOTER region.have a single PROMOTER region.

Ex.) All the genes that produce enzymes Ex.) All the genes that produce enzymes needed to digest lactose are grouped needed to digest lactose are grouped together in the genome of bacteria.together in the genome of bacteria.

► Within the promoter region is a Within the promoter region is a segment of DNA called the segment of DNA called the OPERATOR - this functions like an OPERATOR - this functions like an on/off switch for the transcription on/off switch for the transcription unit – controls the access of RNA unit – controls the access of RNA polymerase to the transcription unit.polymerase to the transcription unit.

We call the promoter, operator We call the promoter, operator and group of related genes an and group of related genes an OPERON.OPERON.

► By itself, the operator (of some operons) By itself, the operator (of some operons) is always switched “on” and RNA is always switched “on” and RNA polymerase binds to the DNA and polymerase binds to the DNA and transcribes all the related genes at once. transcribes all the related genes at once.

► Operator can be switched off by a Operator can be switched off by a protein called a REPRESSOR which binds protein called a REPRESSOR which binds to the operator and blocks the binding of to the operator and blocks the binding of RNA polymerase. The repressor is a RNA polymerase. The repressor is a product of a REGULATORY gene. product of a REGULATORY gene.

► Repressors are constantly produced in low Repressors are constantly produced in low concentrations and in inactive forms. The binding concentrations and in inactive forms. The binding of another molecule activates repressor which can of another molecule activates repressor which can then bind to operator. (This is a type negative then bind to operator. (This is a type negative feedback pathway). feedback pathway).

► This can also work the other way. Some This can also work the other way. Some repressors are made in their active form and are repressors are made in their active form and are always binding to the operator and keeping a always binding to the operator and keeping a transcription unit off. They must be inactivated transcription unit off. They must be inactivated by the binding of another molecule. (An example by the binding of another molecule. (An example of this is the lac operon which is involved in of this is the lac operon which is involved in lactose metabolism in E. coli – read about it!)lactose metabolism in E. coli – read about it!)