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The Origin and Evolution of Viruses

Dr. Mohsin
What is a virus ?
 Viruses are obligate intracellular parasites
 Virus particle is a protein shell, in which the viral genome is
enclosed .
 Virus particles are produced from the assembly of pre-formed
components and do not grow or undergo division
 Viruses lack the genetic information which encodes apparatus
necessary for the generation of metabolic energy and for
protein synthesis
Origins of Viruses

 In contrast to other microbes and multi-cellular organisms, the origin and


evolution of viruses is mostly unknown.
 Our knowledge concerning their origin is lost in a sea of conjecture and
speculations, hardly supported at all with precise scientific evidences.

 For example, viruses have never been detected as fossil particles, probably
because they are too small and too fragile to succumb to fossilization processes.

 Even in fossilized biological materials such as plant leaves or insects in amber,


preserved nucleic acid sequences of viruses have never been detected.

 Hence, evolutionists are limited in their ability to precisely re-construct an


evolutional history of viruses.
Origins of Viruses
 How did these become independent genetic entities?
 The only absolute requirement is an origin of replication in the nucleic
acid.
 However, in spite of all the difficulties in understanding their origin and
evolution, several theories more or less successfully explain the basic
observed facts

There are three theories


1. Regressive theory (Parasitism)
2. Progressive theory (Cellular origins)
3. Co-evolution theory
Regressive Theory (Parasitism)
 The first hypothesis is the so-called theory of ‘‘regressive
evolution’’, which proposes that viruses descend from free-living
and more complex parasites.
 According to this theory, ancestral viruses developed a growing
dependence on host-cell intracellular ‘‘machinery’’ through
evolutionary time, while retaining the ability to auto-replicate.
 Such as mitochondria that have their own genetic information and
replicate on their own .
Regressive Theory (Parasitism) 2
 Viruses degenerated from previously independent life forms.
 Lost many functions.
 Retain only what they needed for parasitic lifestyle.
 The leprosy Bacillus, Rickettsiae and Chlamydia have all evolved in this
direction.
 Mitochondria and chloroplasts are often suggested to have been derived
from intracellular parasites.
 However viruses do not have their own rRNAs or protein synthesis
machinery.
 Also is the question of RNA virus evolution ?.
Progressive theory (Cellular origin)
 The second hypothesis is the so-called theory of ‘‘cell
origin’’, which assumes that viruses reflect their origin from
cellular DNA and/or messenger RNA, which acquired the
ability to auto-replicate, create extracellular virions, exist and
function independently.

 Viruses have been assembled from cellular components into


independent entities capable of moving cell-to-cell and, later,
gaining ability capacity for transmission.
Progressive theory (Cellular origin) 2
 Viruses derived from sub-cellular functional assemblies of
macromolecules that gained the capacity to move from cell to cell.
 Normal cellular nucleic acids that gained the ability to replicate
autonomously and therefore to evolve.
 DNA viruses came from plasmids or transposable elements.
 They then evolved coat proteins and transmissibility.
 Retroviruses derived from retrotransposons and RNA virus from
mRNA.
Co-evolution theory
 Finally, there is the theory of ‘‘independent’’ or ‘‘parallel’’ evolution
of viruses and other organisms, which assumes that viruses appeared
at the same time as the most primitive organisms.
 Viruses evolved independently and in parallel with complex
organisms .
 All of these could be correct! .
 No compelling reason to think that RNA viruses have evolved in the
same way as DNA viruses.
Mechanisms of viral evolution

Evolution: the constant change of a viral population in


the face of selective pressures.

1. Mutation
2. Recombination
3. Reassortment
Why Virus evolution is fast?

• Fast generation time.


• Produce large numbers of progeny.

• High rates of mutation.


Virus-infected cells produce large numbers of progeny

 Infection of a single cell by poliovirus can yield up to


104 viral particles.
 In a person, up to 109 – 1011 particles can be produced
per day.
 Enough to infect every person on the planet.
Evolution requires mutation:
High mutation rates (Genome replication is inaccurate)
• Mutations occur when nucleic acids are copied (i.e. genome
replication).

• Error rate of human DNA polymerase is approximately 10-9 (3


mutations per replication of the human genome).

• Error correction machinery lowers this to 10-11

• Virus RNA and DNA polymerases


are much more error prone.
– RNA dependent RNA pol: 10-3 – 10-6
– DNA polymerases: 10-6 – 10-7
Quasispecies
The term “quasi species” is used predominately for RNA viruses
because of absence of proofreading, many variants are found in an RNA virus
population; the “quasi-species cloud” is the mutant spectrum derived from the
dominant master copy.

• An RNA virus with a genome of 10 kb


• RNA-dependent RNA polymerase (RdRp)
error rate of 10-5
 1 mutant in 1 position for every 10 virions
produced.
• If 109 viral particles produced in a person per day, then
108 mutant progeny are being produced in that one
individual each day of infection.
The Error Threshold:
Error threshold is a mathematical parameter that measures the complexity of the
information that must be maintained to ensure survival of the population.
Fitness: the replicative adaptability of an organism to its environment.
• Too much mutation can be lead to loss of vital information
• Too little mutation can lead to host defenses overcoming the
virus.
• The greatest fitness is when mutation rates approach the
error threshold.
Genetic bottleneck
 A bottleneck effect is an phenomenon in which the population of a species
is drastically reduced to the point where the species is still able to carry on,
but the genetic diversity of the species is severely limited.
 This type of event only occurs when members of the population are killed
at random, and their death has nothing to do with genetic flaws or inability.
 A genetic bottleneck occurs when a virus population is constrained,
resulting in loss of diversity – can be because of:
◦ Vector constraints
◦ Host defense constraints
 A small founder population coming through a genetic bottleneck may give
rise to a skewed population to adapt.
Recombination
 In viruses Genetic recombination is the molecular process by which new
genetic combinations are generated from the crossover of two nucleic acid
strands.
Two type of Recombination:
Depending on the origin of the parental strands, we can distinguish between
 Intra-genomic recombination (wherein the recombining strands belong to
the same genetic unit) and
 Inter-genomic recombination (wherein the fragments have different
origins).
Recombination-1
 Intra-genomic recombination represents a strategy to generate genetic

diversity and to maintain chromosomal integrity.

 Inter-genomic recombination is the most relevant form for both DNA

and RNA viruses because it is capable of generating new variants with

different biological features.

 Several genetic, biological and epidemiological factors can affect the

probability of recombination between different strains, including

genetic homology, population size in the host, co-circulation in the

same geographical area, prevalence in the population and co-infection

rate.
Recombination Template switching: polio virus

Change of templates is referred to as copy choice


Genetic Drift
• Genetic drift: is a mechanism for variation in
viruses that involves the accumulation of mutations
within the genes that code for antibody-binding
sites.
• This results in a new strain of virus particles which
cannot be inhibited as effectively by the antibodies
that were originally targeted against previous
strains, making it easier for the virus to spread
throughout a partially immune population.
Genetic Shift
• Genetic shift: In very serious cases of viral
mutations, something known as antigenic shift
occurs.
• This is a sudden and major change in the
surface antigens of a virus.
• Antigenic shift occurs when two different
strains of influenza virus simultaneously infect
the same cell in your body and undergo a
process called genetic reassortment.
• This is a process whereby two viruses mix and
match parts of their genome.
Reassortant
• If a cell is infected with two different influenza viruses, the
RNAs of both viruses are copied in the nucleus.
• When new virus particles are assembled at the plasma
membrane, each of the 8 RNA segments may originate
from either infecting virus.
• The progeny that inherit RNAs from both parents are
called reassortants.
• This process is illustrated in the diagram, which shows a
cell that is co-infected with two influenza viruses L and M.
• The infected cell produces both parental viruses as well as
a reassortant R3 which inherits one RNA segment from
strain L and the remainder from strain M.
Thanks

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