021b2981020f445b8c6419a5e1bcb423
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Virus Genetic mutation experiment

Postby 021b2981020f445b8c6419a5e1bcb423 » Sat Feb 27, 2021 9:41 pm

Hi!
I’m an high school student from South Korea.
I want to plan an experiment to distinguish whether a specific genetic mutation of a virus is due to selective pressure or if it is just a simple founder effect.
However, I just can’t get it started (have no idea how to plan an experiment.)
I’d be really thankful if you could just simply suggest a guideline or a few ideas that I could try out!

SciB
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Re: Virus Genetic mutation experiment

Postby SciB » Wed Mar 03, 2021 1:17 pm

Hello and welcome to Scibuddies. We're glad to have our Asian friends join us on this forum. Hopefully some volunteers will be able to give you some help on your question.

I'm not a genetics or bioinformatics expert, but I think the way to distinguish a selected mutation from one that is inherited from the founding organisms would be by allele frequency. For example, SARS-CoV2 viruses commandeer a host cell's enzymes to replicate themselves so don't need many genes of their own. But they do have RNA sequences for several enzymes that are essential for making more virus particles and these have to stay more or less the same:
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293463/)
Mutations in these enzymes could have negative effects on the virus, so they tend to stay pretty stable from the original founder sequence. Other viral proteins, like the spike protein that is on the virion surface and binds to a protein on the host cell can undergo mutation to avoid the host's immune system but still be able to attach to and penetrate a person's nasal epithelial cells and cause infection.

A spike protein mutation that caused the virus to be more infectious would be selected for in infected people and show up when that part of the virus RNA was sequenced. This particular mutation would be found only in a cluster of infections, whereas the core founder sequences of the essential enzymes would be present in all varieties including other types of coronavirus like MERS.

I think Cov-2sequencing is being done to determine which variant was involved in a particular infection, so the sequence information may be accessible in GenBank(https://www.ncbi.nlm.nih.gov/genbank/).

I hope some other Scibuddies volunteers, who know more about viral genetics can offer their take on how to distinguish a novel mutation from an essential one. I know there is a lot of bioinformatics and phylogenetic software that you can use online with Genbank sequences as inputs, but I am not very familiar with how to use it.

Let me know more what kind of hypothesis you wanted to test and maybe we can work from there.

All the best,
Sybee

brandimiller610
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Re: Virus Genetic mutation experiment

Postby brandimiller610 » Sun Mar 07, 2021 1:29 pm

I hope you are having a great day! I would like to add to the excellent answer given by the expert SciB. I am unsure if you utilized the tips from a similar project here on ScienceBuddies, but I found the following project that may help (https://www.sciencebuddies.org/science- ... nical#help)

Viruses evolve, or mutate, due to natural drift/mutations and selective pressures of the host (i.e. our immune systems); it is important to study the mutation of viruses to map their evolutionary changes, understand how they are transmitted from host-to-host, and aid in the development of vaccines and other therapeutics. From a bioinformatics standpoint, whole genome sequencing (WGS) is probably the highest throughput methodology available for analyzing genetic variation between viral strains. The CDC/WHO conduct "surveillance" for the flu viral strains every year -- more specifically, they determine the genome sequences of the strains and then do genetic characterization to determine similarities between the viruses, track their evolution, and develop vaccines (https://www.cdc.gov/flu/about/professio ... zation.htm).

With this background information in mind, I think one feasible approach for your research question incorporates viral genetics and functional biology and ties the two together. Once you choose your virus of interest, you should study the proteins that make up the virus (you can use NCBI virus for sequencing: https://www.ncbi.nlm.nih.gov/labs/virus/vssi/#/) and align two protein sequences (mutants) of your choice virus. Lower amounts of genetic variation indicate that founder effects may be present between two mutations, while higher variation may indicate that selective pressure has taken place. Another way to possibly determine if selective pressure is prominent is to analyze the functional relationships between the mutations. Note the key differences in the amino acid sequences between the strains and determine which proteins/amino acids are affected and how these mutations alter the overall functioning of the virus. For example, if you were to choose SARS-CoV-2, does one mutation of the SARS-CoV-2 virus alter the sequence of the spike protein -- if so, how does this mutation change the function of the spike protein in viral entry (i.e. is the virus less infectious, unable to enter the host cell as easily, etc). Mutations that cause functional changes often arise due to selective pressure so that the virus can survive, continue to be transmitted from host-to-host, and bypass/hijack the human immune system. Human behaviors, such as traveling, also affect the genetic makeup and mutation of a virus, so it is important to take this into account when studying viral genetics.

Again, these are just my ideas and I hope some of the information helps you devise a science fair project. I really recommend reading the links I have added, as I believe they are pertinent to your question. Let me know if you have any questions. It may be easier to develop a project once you have a narrower focus, select a virus, and formulate a hypothesis.

--Brandi


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