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Virus Evolution and Genetics (MCB3023S) notes
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Comprehensive lecture notes for the Virus evolution and genetics module covered in MCB3023S. These notes cover all content taught in lectures as well as additional materials (powerpoints, textbooks) required to succeed. These notes were created by a student who achieved a distinction in this course.

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  • February 8, 2024
  • 24
  • 2022/2023
  • Class notes
  • Ed rybicki
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MCB3023S

Virus evolution and Genetics

A re-introduction to viruses, virus evolution and origin of components
- viruses are acellular organisms with nucleic acid genomes, which make particles to protect the genome and transfer it
between cells, while they do not exhibit all of th supposed attributes of cellular organisms, viruses are independent entities
that are not limited to one host
- virus-like agents include plasmids, satellite viruses, satellite nucleic acids, viriods and retroelement
- the virocell is the virus taking over the cell in order to replicate

Paper by Krupovic and Koonin
- titled “the entire history of life is the story of virus-host co-evolution. Therefore, the origins and evolution of viruses are an
essential component of this process”
- virus genomes typically consist of distinct structural and replication modules that recombine frequently and can have
different evolutionary trajectories
- although the replication modules of at least some classes of viruses might descent from primordial selfish genetic
elements, bona fide viruses evolved on multiple, independent occasions throughout the course of evolution by the
recruitment of diverse host proteins that became major virion components

Virus genomes
- virus genomes range in size from around 1800 nucleotides (ssDNA circoviruses) up to
2.5 million nucleotides (dsDNA pandoraviruses)
- viruses are the only organisms on this planet to still have RNA as their sole genetic
material
- they are also the only autonomously replicating organism to have single-stranded DNA
- given that viruses have separate origins that are distinct from one another and such a
huge diversity, they have the largest variety of genome types of all organisms
- viruses can have double and single stranded DNA, which can be linear or circular
- viruses can have an RNA genome, which is unique amongst organisms, which can also
be double or single stranded

Virus replication
- given the wide variant of genome types, viruses have a wide variety of replication mechanisms; there are 7 distinct modes
of replication
- class III only occurs in viruses, no other cellular organism does this, and viruses have to encode the enzymes
- class III, IV and V have to encode their own RNA dependent RNA polymerase (RDRP)
- class VI and VIII are quite closely replated and are related to a whole host of cellular retro elements

Virus origins
Prebiotic soup
- Prebiotic soup > RNA in protocells > DNA in protocells > Bacteria & Archaea
> Eukarya
- this RNA would have been capable of replicating and could have given rise to
viruses and those RNA protocells gave rise to DNA in protocells, which
replicated itself and gave rise to another class of viruses
- those DNA protocells gave rise to archaea and bacteria which replicate by
themselves and both produced new sets of viruses
- archaea gave rise to eukarya, which was then promptly colonized by bacteria in
terms of mitochondria and chloroplast) and these organisms, especially eukarya,
gave rise to a large number of new viruses




Elements involved

,- a scenario for the origin of viruses from selfish replicators upon acquisition of capsid protein genes from cellular life forms
at different stages of evolution
- for example, at a pre-cellular stage, there is a community of replicators (no true viruses), these then emerged primitive
cells acquired cellular protocapsid genes (the origin of the first viruses)
- then you have the evolution of modern cells (bacteria, archaea and eukarya), continuous emergence of new viruses and
diversification of the virosphere
- replication machinery proceeds to pick up other components, one of which is the capsid protein, to make new kinds of
viruses
- although the replication modules of at least some classes of viruses might descend from primordial selfish genetic
elements, bona fide viruses evolved on multiple, independent occasions throughout the course of evolution by the
recruitment of diverse host proteins that became major virion components
- NB: this means that different viral “replication modules” could pick up a wide variety of “structural modules” from cells
and from each other

Capsid protein origins
Example 1
- so, for example, have cellular homologs of the retroviral proteins
constituting the Gag polyprotein (A)
- the Gag polyprotein encodes all of the structural proteins of retroviruses
- they are divided into MA for matrix, CA for capsid and NC for
nucleoprotein
- B: shows the structural comparison of the matric protein (Upper) of mouse
mammary tumor virus with the N-terminal DNA-binding-domain (Lower) of
the tyrosine recombinase of V. cholerae
- C:P structural comparison of a dimer of the CA C-terminal domain of HIV-1
with the dimer of the human SCAN domain protein
- D: structural comparison of the NC protein of HIV with the human pluripotency factor Lin28
- all structures are colored using the rainbow scheme from blue (N terminal) to red (C terminal) and the corresponding
identifies are shown

Example 2
- A is a selection of viral SJR (single jelly roll) CP (coat protein)
structures, the rightmost structure corresponds to the virion of STNV
- B is a selection of cellular SJR protein structures, the rightmost
structure corresponds to the 60-subunit virion like assembly of the
human sTALL-1 protein

Example 3
- structural comparison of the Ebola virus MA protein with CypC
- topology diagrams (left) and structural models (right) are colored using the
rainbow scheme from blue (N terminus) to red (C terminus)
- the hairpin inserted in CypC is colored black
- shows the Ebola virus matric protein, and this is very, very similar to the
Cyclophilin C structure, which is a eukaryotic protein and it is almost certain that
the Ebola virus matric protein derived from a protein like Cyclophilin C

Replication of viruses 1: Classes I-III
Seven basic replication strategies Distribution of viruses by replication type




The central Dogma
- “the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be
possible, but transfer from protein to protein, or from protein to nucleic acid is impossible”
- there are two things wrong with the Central Dogma
- also stated (incorrectly) because DNA > RNA > protein

, Cell information flow
- the information repository is genomic double stranded DNA for any cell information flow
- this can give rise to mRNA via transcription using RNA polymerase
- also makes things such as tRNA, miRNA etc.
- mRNA is translated into protein via cellular ribosomes which are dependent on tRNA to function as well as rRNA to make
protein
- the first of the crack in the central dogma appeared in that it appears that reverse transcription is actually a natural part of
almost all cells activities
- and replication of the genomic double stranded DNA by DNA dependent DNA polymerase

Virus information flow




- Viruses that infect Prokaryotes are mostly dsDNA
viruses.
- Viruses that infect Eukaryotes are mostly RNA viruses
but ssDNA and dsDNA viruses are
also common
- Schematics of several viral classification systems explored in this study. -
(A) The Baltimore classification divides all viruses into seven groups based
on how the viral mRNA is produced
- DNA strands are denoted in red (+ssDNA in darker shade of red than -
ssDNA).
- Similarly RNA strands are denoted in green (+ssRNA in darker shade of
green than -ssRNA).
In the case of Baltimore groups 1,2,6, and 7, the genome either is or is
converted to dsDNA, which is then converted to mRNA through the action
of DNA-dependent RNA polymerase.
- In the case of Baltimore groups 3, 4 and 5, the genome is or is converted
to +ssRNA, which is mRNA, through the action of RNA-dependent RNA
polymerase.
- (B) Nucleotide type classification divides viruses based on their genomic
material into DNA and RNA viruses.
- Baltimore viral groups 1, 2, and 7 are all considered DNA viruses, and the
remaining viral groups are considered RNA viruses.
- (C) Host Domain classification groups viruses based on the host domain
that they infect.
- Three groups are formed: eukaryotic, bacterial and archaeal viruses


Class I: dsDNA genomes
- this holds true for genome sizes of 5kb to 2500 kb
- primary transcription (usually) by host enzymes
- translation of early (regulatory) proteins
- viral genomic DNA replication follows, usually by host enzymes for simpler viruses
- late transcription, usually mediated by viral proteins, to produce late mRNA
- synthesis of late (structural) proteins
- assembly of structural protein and DNA into virions

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