Wednesday, March 29, 2023

POPULATION SIZE

 (Prepared by: Noopur, 20220901022)

How does population size affect viruses?

The spread of deadly virus can be enhanced with the increasing number of human beings.

Population genetic diversity plays a prominent role in viral evolution. This diversity is subsequently modulated by natural selection and random genetics drift, whose action in turn depends on population size.

What happens if virus mutation take place due to population size?

Virus mutations create genetic diversity, which is subject to the opposing actions of selection and random genetic drift, and this is affected by the size of the virus population. The genetic diversity can lead to negative or positive virus-virus interaction. Size of viral population determines the genetic drift, which in turn depends on spatial structure, population size bottlenecks during host-to-host transmission. Therefore, selection and drift are conditioned by population size.

The high mutation rate of viruses, coupled with short generation times and large population sizes, allow viruses to rapidly adapt to the host environment.

What is population size bottlenecks?

Population bottlenecks leading to a drastic reduction of the population size, which are common in the evolutionary dynamics of natural populations; there occurrence is known to have implication for virus evolution. It occurs when a population size is reduced for at least one generation.


What if population size is large? Or small?

When the population size is large, selection becomes predominant and random genetic drift become less common. When the population size is small, random effects may obscure the effects of selection. The population sizes of RNA viruses are often very large, factors such as variation in replication potential among variants, differences in generation time among infected cells and population bottlenecks, might lead to an effective population size.

Despite virus enormous population sizes, viruses experience significant genetic drift. This is because the strength of drift depends on the effective population size, not on the census size.

Viral population genetic diversity plays a major role in ability of viruses to cause disease. In general pathogens evolve faster than their hosts owing to their shorter generation times and higher population size

One unique characteristic of viruses is their MOI, which is the ratio between the number of viruses and the infecting cells. MOI can be subject to the constantly changing size of the virus population.

The viral evolution creates huge population size within the infected host. However, this huge population size is punctuated by frequent bottlenecks.[1], [2]

 

References

[1]        [1] A. Stern and R. Andino, “Viral Evolution: It is All About Mutations,” in Viral Pathogenesis: From Basics to Systems Biology: Third Edition, Elsevier Inc., 2016, pp. 233–240. doi: 10.1016/B978-0-12-800964-2.00017-3.

[2]        [2] A. Moya, E. C. Holmes, and F. González-Candelas, “The population genetics and evolutionary epidemiology of RNA viruses,” Nature Reviews Microbiology, vol. 2, no. 4. pp. 279–288, Apr. 2004. doi: 10.1038/nrmicro863.

 

MULTIPLICITY OF INFECTION

(Prepared by: Srushti Bhoite, 20220901003)


                                             Source: https://i.ytimg.com/vi/rfw_rcP5XOA/maxresdefault.jpg

It is defined as the ratio of infectious virions to cells in a culture. When the MOI is high the cell is infected with multiple viruses but when MOI is low the cell is infected with only one virus. In recombining viruses if MOI is higher it would lead to higher recombination and eventually it will lead to more efficient selection, removal of deleterious alleles and emergence of strains with more virulent phenotype.


It may have contrary effects like inferior genotypes are rescued and maintained in population. Complementation at high MOI leads to multiplication of defective particles. High MOI also leads to multiple genomic copies of same gene in one infected cell. In phage if copy number is one it will be lytic and kill the host cell and if it exceeds one it becomes lysogenic and host cell remains alive.


The number of phage infecting each bacterium could be calculated from Poisson equation: P(n) = (m*n × e-m)/n! where P(n) is the probability that the cell will be infected with exactly “n” phage and “m” is the average number of phage per cell (that is MOI). 


High MOI leads to complex effects on genome selection Distribution of viral particles at different sites of an infection are unknown and will affect MOI and efficiency of selection. The population with highest fitness in the original host does not adapt well in new hosts whereas low frequency genotypes from original host may adapt well in new host. Different types of viruses will be affected differently by MOI.  [1], [2]

     

           Source: https://kb.10xgenomics.com/hc/article_attachments/360043450932/MOI.png


References

[1]      [1]  P. Shabram and E. Aguilar-Cordova, “Multiplicity of infection/multiplicity of confusion,” Molecular Therapy, vol. 2, no. 5. pp. 420–421, 2000. doi: 10.1006/mthe.2000.0212.
[2]  A. Stern and R. Andino, “Viral Evolution: It is All About Mutations,” in Viral Pathogenesis: From Basics to Systems Biology: Third Edition, Elsevier Inc., 2016, pp. 233–240. doi:10.1016/B978-0-12-800964-2.00017-3.










Sunday, March 26, 2023

ROLE OF MUTATION IN EVOLUTION

                                                                                          (Prepared by:Priya Prakash, 20220901007)

Viral evolution is driven by the accumulation of genetic changes, which can lead to the emergence of new strains or subtypes of the virus. Mutations play a significant role in viral evolution. Mutations can affect various aspects of viral biology, such as virulence, transmission, and host range, and can also lead to drug-resistant strains. Understanding their impact is essential for developing effective strategies to control viral infections.

But what’s Mutations in Viruses?

               Mutations are the basis for evolution and natural selection. An alteration in the genetic material (the genome) of a cell of a living organism or of a virus that is more or less permanent and that can be transmitted to the cell’s or the virus’s descendants is known as Mutation. Viruses have high mutation when compared to any life form. This helps it to rapidly evolve and adapt quickly to the host system. 

Are Mutations Good For Viruses?

                      Mutations in viruses, when they make copies of themselves can be both beneficial and harmful. Some such changes can lead to efficient reproduction or lead to dead ends or harmful outcomes which limit an organism’s ability to survive. We all know that there was once confusion on whether viruses should be considered as living or non-living organisms. But their mutation ability was considered as the most compelling arguments for viruses to be classified as living organisms.

But Why Mutations?

                    Mutations help viruses to be more effective than the previous generation in moving from host to host, speed up reproduction and thereby extend its life. It also helps them to be more effective in adhering to host surfaces. The example for this is quite well known, the spike protein of COVID-19. Mutations also have the ability to increase the probability of viruses evading the immune responses and vaccines.  

                      The illustration below depicts how mutation happens in a virus.


Let’s discuss about variations in genes due to mutations.

                   Genetic variety is produced by viral mutations but comes under the pressure of selection and random genetic drift which is directly influenced by the number of virus populations. Large populations will exhibit selection more frequently and less frequently than small populations. Thus, harmful alleles will be successfully eliminated from the population while adaptive alleles will have a chance to rule the community. Random effects, however, could mask the effects of selection in small populations. The population's frequency of mildly harmful alleles may unexpectedly increase under these circumstances, while adaptive alleles could accidentally disappear.

                  The abundance of mutants, which is also referred to as a "quasispecies," has the capacity to encode viruses with increased treatment resistance or the capacity to elude neutralising antibodies produced by the host. This challenges efforts to develop efficient vaccinations since evolution has the potential to significantly expand the number of virus serotypes that are present in human populations. In addition, viruses' special capacity for change enables them to pass over barriers separating species, leading to zoonotic diseases [1].

                    The mutation together with selection will determine which mutations will survive in the viral population.

Have you heard about Lethal Mutagenesis?

                         Lethal mutagenesis is a phenomenon in which an increase in the mutation rate of a virus or other pathogen leads to its extinction. It has been proposed as a potential therapeutic approach for treating viral infections, including those caused by HIV, influenza, and hepatitis C. However, there are many challenges associated with implementing this approach, such as balancing selective pressure on the virus with the potential for it to evolve resistance, and concerns about the safety and efficacy of the mutagenic agents themselves [2].


References










"How So Strong??"

            (Prepared by:  Priya Prakash, 20220901007 )            Created using BioRender.

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