Abstract

Over time, viruses evolve. Their evolution is influenced by both neutral drift, the natural mutation rate of the virus, and selective pressure from the hosts' immune systems. Scientists study a virus's genomic evolution—the changes at the nucleotide and amino acid level—to better understand how the virus is spreading and the clinical implications. You can use public databases and tools to do the same type of tracking and analysis of COVID-19 that scientists around the world do.

SARS-CoV-2, the virus that causes the disease COVID-19, has been sequenced often from patients around the world. By comparing sequences from different patients, at the amino acid level, you can see whether there are any changes. If you find a change, there are many follow-up questions to ask, such as:

• When and where did the mutation arise?
• Has the mutation become more or less prevalent over time? If the frequency of the mutation has increased, it could be due to selective pressure, be advantageous to the virus, and have clinical implications. Or it could simply be due to a founder effect. Think about how you might distinguish between selective pressure and founder effect, including what laboratory experiments would help (even if doing the actual experiments is beyond the resources you have access to).
• What are the possible clinical implications of the mutation? What kind of functional differences might the mutation impart? Is there any published data about the mutation?

Here are some tips to help you start your scientific exploration:

• Read up about the SARS-CoV-2 proteins. Which ones are known to play a role in COVID-19 clinical outcomes? Two good starting places are Chemical & Engineering News's article What do we know about the novel coronavirus's 29 proteins? and ViralZone's SARS coronavirus 2 interactome page.
• Access SARS-CoV-2 protein sequences from COVID-19 patients using the repository found online at NCBI Virus's SARS-CoV-2 page.
• Use samples with early collection dates, particularly those from China, as your baseline sequences from which to compare the other sequences.
• Work with the protein sequences, as opposed to the nucleotide sequences, as some nucleotide mutations do not result in amino acid changes.
• You can choose sequences using the filters at the NCBI Virus website and then use the "Align" option to match up the sequences right there, rather than using another tool. To learn how to use the alignment tool, consult NCBI Virus's Help page.
• Compare SARS-CoV-2 genomes from different countries. While a mutation that arises and expands in multiple populations is more likely to be due to natural selection, travel by hosts is a confounding factor.

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