Virology - Viral origins, genetics, diversity and evolution Flashcards
My learning goals
- Viral origins
- What is a viral genome and what does it encode
- The functions of encoded viral genes
- Know the seven classes of viral genomes and how mRNA is made from the genome
- How the genome is copied to make more genomes (DNA vs RNA)
- Understand how mutations and interactions between viruses affects viral diversity
- Definitions of the types of mutations
Principles of viral genetics
- A universal function of the viral genome: encode for specific proteins
- All viral genomes must be copied to produce mRNA that can be read by the host ribosomes
-There are 7 major types of viral genomes
Baltimore system integrates these 2 principles
-All viruses with RNA genomes must either encode an RNA-dependent RNA polymerase(to synthesize RNA or reverse transcriptase (RNA-DNA)
Viral Origins
-An Enigma - a mystery
- There are no fossils to study
- Signs of common ancestry resides in the aspect of the protein structure
- 3 hypotheses/theories proposed
- Virus first Hypothesis
- Relics / remnants of pre-cellular life forms
- Primordial “RNA world”
- Existed as self-replicating units which became more organized and more complex over time
- Present RNA viruses could be relics of the RNA world
**Later rejected: Viruses are obligate parasites
- Reduction Hypothesis
- May be descendants of previously free-living organisms that adapted a parasitic replication strategy
- Organisms developed a symbiotic relationship
- Over time the relationship became parasitic with one organism depending on the other and lost essential genes
-Poxviruses illustrate this hypothesis:
>large genome size with greater complex
>depend less on the host cell for replication
- Reduction Hypothesis REJECTED because?
-Parasites that derived from cells would have retained their cellular characteristics.
- No known intermediate form between cells And viruses.
- Viruses don’t contain any remnants of cellular life forms.
- Progressive Theory aka escape theory
- Viruses originated through a progressive process
- Suggests that fragments of genomic material from large genomes gained the ability to leave one cell and enter another
- This explains the ability of viruses to integrate their genome into the host cell genome.
- Most favored theory
What information is encoded in a viral genome? what is not?
Gene products and regulatory signals required for:
- Replication
- Efficient expression of the genome
- Assembly and packaging of the genome
- Regulation and timing of the replication cycle
- Modulation of host responses
- Spread to other cells and hosts
Information not contained in viral genomes:
>Genes encoding for protein synthesis machinery( e.g. ribosomal RNA and translational proteins)
> Genes encoding proteins of energy metabolism
Viruses do not independently undergo metabolism they require a host to do that.
Terminology explaining mRNA + and - and DNA and ambisense RNA.
- mRNA: positive (+) strand because it can be translated ( RNA is ready!)
- Negative (-) strand cannot be translated and must first be copied to make the (+) strand.
- Ambisense RNA contains both (+) and (-) sequences.
- A strand of DNA is considered as a (+) strand.
The 7 classes of viral genomes
- dsDNA —- dsDNA is transcribed by either host DNA polymerase( generally smaller viruses because of limited space) eg. Polyoma and papilloma.
Other larger DNA genomes encode their own DNA polymerase- the genome is larger - herpesviruses.
- Gapped dsDNA [partially double stranded] —– Gapped dsDNA (7th) Hepadnavirus (hepatitis B). Partially double strand. This genome cannot be transcribed- fill the gap – has an attached RNA – RT – RNA- DNA.
- ssDNA —- Parvovirus linear ssDNA- small genome. genome first made double-stranded by cellular enzymes – double-stranded and transcribed into mRNA.
- dsRNA —- Ds RNA( Reovirirdae) + and – strand ds RNA cant be translated directly into MRNA therefore have packaged their own RdRp.
- ss(+)RNA
- ss(-)RNA
- ss(+)RNA with DNA intermediate
Structure and complexity of viral genomes.
- Linear
- Circular
- Segmented
- Gapped DNA ( 7th Baltimore class)
- Single-stranded (+) strand
- Single-stranded (-) strand
- Single-stranded, ambisense ( ambisense RNA contains both (+) and (–) sequences)
- Double-stranded
- DNA with short RNA segment
Viral evolution
-Evolution is driven by various pressures on viruses to mutate.
Examples:
- Drug pressure
- Immune Pressure
- Climate Change
- Random mutation events (e.g. error-prone replication of RNA viruses)
- Mutagens e.g. UV light, chemicals
Sources of diversity in viral genomes
- Mutations: A change in the genotype of an organism not resulting from recombination. In short, it is a substitution of one nucleotide for another.
- Effect of a mutation: may lead to a change in the structure of the protein coded for by a nucleotide sequence or modify gene regulation.
- There are different types of mutations
Types of mutations
- Substitution
- Insertion
- Deletion
- Inversion
a. Single nucleotide polymorphism aka point mutation. = When a single nucleotide in a genome differs between members of a species.
b. Indels (insertion and deletions) = frameshift mutations.
- Involves single nucleotides or small blocks or nucleotides.
SNP - Single nucleotide polymorphism
Transition and Transversion
- Transition
=a mutation changing a purine to another purine, or a pyrimidine to another pyrimidine
- A ↔ G C ↔T(U)
2. Transversion - A mutation changing a purine to a pyrimidine or a pyrimidine to a purine
-A ↔ C A ↔ T(U)
G ↔ C G ↔ T(U
