Genetics of Viruses and Bacteria

1.         Viruses

            a.         Structure (Fig. 17.2)

                        i.         Viruses are made of a protein shell (called a capsid) enclosing the nucleic acid. Capsids are built from a large number of protein subunits and exist in a variety of shapes.

                        ii.        Some viruses, especially those which infect animals, have a membrane (called an envelope) surrounding the capsid. The envelope is derived from the host cell membrane and contains both viral and host proteins and glycoproteins.

                        iii.       Each type of viruses is able to infect only a limited range of host cells. Proteins in the capsid or envelope bind with receptors on the surface of the cell and are necessary for a virus to recognize and infect it’s host cell. Some viruses have a host range that includes several species while some are so specific that they recognize only one species or one specific type of tissue in a species.

            b.         Genome - the genome of viruses can be ssDNA, dsDNA, ssRNA, or dsRNA and viruses are called DNA viruses or RNA viruses depending on their nucleic acid.

            c.         Reproduction

                        i.         Viruses lack enzymes, ribosomes and other organelles necessary for life. They are intracellular parasites, - able to reproduce only inside a host cell. Infection begins when the viral genome manages to enter the host cell and begins to direct the host cell machinery to make new capsid proteins and copies of the viral genome. Remember that to produce new virus particles, the virus gains all the necessary enzymes, nucleotides, amino acids, energy, etc. from the host.

                        ii.        After the capsid proteins and nucleic acid are synthesized, they usually spontaneously assemble into new virus particles.

                        iii.       Hundreds or thousands of new viruses then exit the cell, often destroying the cell in the process.

                        iv.       The new virus particles are then free to infect more cells.

                        v.         Lytic cycle (Fig. 17.4)

                                    (1)       This life cycle ends with the death of the host cell.

                                    (2)       Viruses with this type of life cycle are called virulent viruses.

                                    (3)       The bacteriophage T4 provides a good example. The virus attaches to the host cell and injects it’s nucleic acid. The viral genes take over the cell, directing it to make viral proteins and nucleic acid which then self-assemble into new viruses. One viral gene codes for an enzyme which digests the cell wall. Without a cell wall, the bacterial cell lyses (hence, lytic cycle) as a result of the osmotic uptake of water. The lysed cell then releases up to 200 phages to infect nearby cells.

                                    (4)       Bacterial defenses

                                                (a)       There is selective pressure to develop new receptors which viruses do not recognize.

                                                (b)       Restriction enzymes recognize and cut up DNA that does not belong to the bacterium.

                        vi.       Lysogenic cycle (Fig. 17.5)

                                    (1)       In this cycle, the viral genome is copied without killing the cell.

                                    (2)       Viruses with this type of life cycle are called temperate viruses.

                                    (3)       The bacteriophage lambda provides a good example. This virus can follow either a lytic or lysogenic cycle. The phage attaches to the surface of the host cell (E. coli) and injects it’s DNA. During a lytic cycle the phage follows the pattern outlined above. During a lysogenic cycle, the viral genome is incorporated into the host cell genome and is called a prophage. One gene codes for a protein that suppresses most of the other prophage genes. Each time the bacterium divides, the phage DNA is replicated and passed on to the daughter cells. This way, the virus increases in numbers without destroying the host cells. (diabolical) A chemical or environmental trigger of some kind causes the prophage to exit the lysogenic phase and begin a lytic infection.

            d.         Animal viruses

                        i.         Viruses with envelopes (Fig. 17.6)

                                    (1)       Once the virus binds with the host cell, the envelop fuses with the host cell plasma membrane, transporting the capsid and nucleic acid into the cell. After cellular enzymes remove the capsid, the viral genome takes over the cell. The ER makes proteins for the new envelopes and clusters them in patches on the plasma membrane. New viruses bud (like exocytosis) from the areas of these clusters. Thus, the envelop is derived from the host cell membrane although some of the proteins contained in it are of viral origin. Note that this cycle does not necessarily kill the host cell.

                        ii.        RNA viruses (note that some phages and most plant viruses are RNA viruses) (Fig. 17.7)

                                    (1)       RNA viruses known as retroviruses contain an enzyme called reverse transcriptase which can transcribe DNA from an RNA template. The host RNA polymerase then transcribes the DNA into RNA which function as both mRNA for the synthesis of viral proteins as well as for new viruses.

            e.         Treating and preventing viral diseases

                        i.         Vaccines are the primary preventative measure for viral disease. A vaccine is made of either a harmless version of the virus or a part of a virus which will trigger an immune response. The immune system will be able to defend against infection during a subsequent exposure. Other than some drugs which interfere with the synthesis of viral nucleic acid, there is very little that can be done to cure viral infections once they occur.

            f.         Emerging viruses. There are three processes that contribute to the emergence of new viruses. In many cases, human activity contributes to the spread of viruses by transporting them to other places or by invading habitats.

                        i.         An existing virus evolves to be unrecognizable to an individual exposed to a previous version. Influenza virus is a good example.

                        ii.        An existing virus spreads from one species to another.

                        iii.       An existing virus escapes from a small, isolated population to become widespread. HIV is an example.

            g.         Viruses and cancer. Several viral genes are known to trigger cancer in cells. The genes, called oncogenes, code for proteins that regulate cell growth. When the viral genome is inserted into the host genome, the oncogenes can stimulate cell growth. Alternatively, insertion may activate oncogenes already present in the host genome.

            h.         Viroids - Plant pathogens that are tiny molecules of naked RNA, several hundred nucleotides in length, that are somehow infectious. They have sequences similar to introns so it is suspected that they are, in fact, escaped introns.

            i.         Prions - Infectious agents that are proteins. The lack of nucleic acid makes prions difficult to explain. They appear to be misshapen versions of normal cell proteins that somehow converts the normal protein into the prion version. By positive feedback, more and more of the normal protein molecules are turned into prions.

            j.         Origins of viruses

                        i.         Because viruses depend on host cells, it is likely that they evolved after the first cells. They possibly originated from fragments of cellular nucleic acid that could move from one cell to another. Later, the virus could have evolved genes for capsid proteins. Evidence for this comes from the observation that a viral genome has more in common with the host genome than with the genome of a virus infecting other hosts.

                        ii.        Plasmids and transposons are likely candidates for the origin of viruses. Plasmids are small, circular pieces of DNA that are separate from chromosomes. Present in bacteria and yeast, they can replicate independently and are regularly transferred between cells. Transposons are segments of DNA that can move from one location to another in a genome.

                        iii.       The relationship is that viruses, plasmids, and transposons are all mobile.

2.         Bacteria

            a.         Evolutionary mechanisms

                        i.         Short generation time - although the probability of mutation at any locus is very low, bacteria reproduce so quickly that mutations occur regularly. Note that this is quite different from the situation in a slowly reproducing species such as humans where mutations plays a very small role in evolution. In humans, most variation results from recombination of alleles.

                        ii.        Genetic recombination - i.e., combining the genetic material from two individuals into the genome of one individual.

                                    (1)       Transformation - the uptake by the bacterium of naked DNA from the environment. Some bacteria have membrane proteins specialized for this function.

                                    (2)       Transduction (Fig. 17.10) - a phage transfers bacterial genes from one host to another.

                                                (a)       At the end of the lytic cycle, the viral nucleic acid is packaged into capsids. Sometimes a piece of the host cell’s degraded DNA is packaged along with or instead of the viral nucleic acid.

                                                (b)       At the end of the lysogenic cycle, when the phage genome is excised from the host chromosome, sometimes it takes with it a section of the host genome.

                                    (3)       Conjugation (Fig. 17.12a)

                                                (a)       During conjugation, two bacterial cells join temporarily and a plasmid is transferred from one to the other. The donor cell uses sex pili to attach to the recipient and the two join by way of a cytoplasmic bridge.

                                                (b)       Plasmids generally carry either genes required for the production of sex pili or for antibiotic resistance.

                                    (4)       Transposons

                                                (a)       in bacteria, transposons can move from one location to another on the chromosome, from the chromosome to a plasmid, from a plasmid to the chromosome, or from one plasmid to another.

                                                (b)       In this way, genes can be transferred from one cell to another.

            b.         Control of gene expression

                        i.         In order to cope with changes in the immediate environment, bacteria must be able to respond to those changes. For instance, a bacterium deprived of a certain amino acid will synthesize that amino acid from other molecules. When that amino acid is present, however, the cell will stop producing it to preserve resources.

                        ii.        Control occurs on two levels:

                                    (1)       A cell can vary the number of specific enzyme molecules it produces. i.e., they regulate gene expression.

                                    (2)       A cell can vary the activities of existing enzymes.

                        iii.       Operons

                                    (1)       Metabolic pathways occur in a series of steps. The genes coding for the enzymes involved in these steps are often clustered in a group. These genes are called structural genes. This way, transcription produces a single mRNA containing all five genes. They are associated with a single promoter so that the genes can be controlled as a unit by turning on or off a single switch. The switch is called an operator. Together, the structural genes, promoter, and operator are called an operon.

                                    (2)       Normally, an operator is on; RNA polymerase can bind to the promoter and transcribe the structural genes. When a protein called a repressor binds to the operator it blocks the attachment of RNA polymerase. The repressor is the product of a gene called a regulatory gene.

                                    (3)       Repressible versus inducible enzymes.

                                                (a)       Repressible enzymes (Fig. 17.17) are those whose synthesis can be repressed (or inhibited) by a metabolic end-product. They are generally involved in anabolic pathways. By stopping the production of an end-product when it is already present, the cell can use resources for other things.

                                                (b)       Inducible enzymes (Fig. 17.18) are those whose synthesis can be induced by some molecule. They are generally involved in catabolic pathways. The cell produces the enzymes only when the nutrient is present.

                                                (c)       These are both examples of negative gene control because the protein interacting with the genome turns off the operon.

                                    (4)       Positive gene control (Fig. 17.19). For some operons, transcription can be increased or decreased in addition to being switched on or off. Catabolite activator protein (CAP) binds to the promoter of the lac operon and improves the binding of RNA polymerase. This is positive gene control because when CAP binds to DNA it increases transcription.