Coronavirus Evolution and the COVID-19 Pandemic1

Where did the new coronavirus come from?In 2019, a new type of infectious disease began to cause human illness and death. Scientists soon discovered that this disease was caused by a new type of coronavirus. The new disease was named COVID-19 for COronaVIrus Disease discovered in 2019. By February 2021, COVID-19 had caused half a million deaths in the US and 2.5 million deaths worldwide.

1. Suggest one way that the new type of coronavirus could have originated.

To learn more, watch the video, “Where do new viruses come from?” (https://www.youtube.com/watch?v=NJLXdsO1GBI).

2a. This figure shows a cross-section of a coronavirus. Circle a spike protein (S).

2b. Which molecule in the coronavirus provides the instructions for making the spike proteins?

2c. The spike proteins are one half of the Velcro mentioned in the video, and the other half of the Velcro consists of molecules on the surface of human cells. What happens after the coronavirus spike proteins bind to molecules on the surface of human cells?

3a. The video describes spillover infections. What is a spillover infection?

3b. Describe the sequence of steps that result in a spillover infection.

3c. Give examples of diseases that have been caused by spillover infections in the past.

1 By Dr. Ingrid Waldron, Dept Biology, University of Pennsylvania. © 2021. A Word file and Teacher Preparation Notes with instructional suggestions and biology background are available at https://serendipstudio.org/exchange/bioactivities/coronavirusOrigin.

Inside a human cell, the coronavirus RNA is copied and the genes in the RNA give the instructions to make the coronavirus proteins. Then, the RNA and proteins combine to make new coronaviruses.

If a mistake occurs when the RNA is copied, the RNA copy will have a different sequence of nucleotides. This is called a mutation. This figure shows a short piece of the original RNA (on the top) and a copy with a mutation.

4. Mark the mutation with an asterisk (*).

A mutation in the spike protein gene results in a different amino acid in the spike protein. The change in amino acid can improve spike protein binding to molecules on the surface of human cells.

5. How do mutations contribute to a coronavirus spillover infection? Give a specific example.

The first row of the figure below shows eight of the coronaviruses from a bat that a person inhaled into his/her nose. Most of these coronaviruses have the B version of the spike protein gene. However, two of the coronaviruses have mutated versions of the spike protein gene (H and N).

The three versions of the spike protein gene give the instructions to make three versions of thespike protein. The table on the right describes whether each version of the spike protein can bind to molecules on the surface of bat cells and human cells.

Spike Protein Bat Cells Human CellsB Yes NoH No YesN No No

6a. In the top row of the figure, use X to cross out each coronavirus that will not be able to enter a human cell.

6b. For each coronavirus in the top row that will be able to enter a human cell to be reproduced, draw arrows to the coronaviruses that will be produced by the person’s cells.

6c. In the bottom row, label each coronavirus produced by the person’s cells with the version of the spike protein gene that it would have.

This is an example of natural selection. Due to natural selection, a mutation that increases the ability of a coronavirus to enter cells and be reproduced will become more common in the population of coronaviruses.

2

Since mutations are random changes in the RNA, most mutations of the spike protein gene result in a spike protein that does not bind well to molecules on the surface of either bat cells or human cells. Coronaviruses with this type of mutation would be eliminated by natural selection.

7. Many types of animals are infected by coronaviruses, and many many mutations have occurred in the trillions of coronaviruses in these animals. Explain why most mutations of coronavirus genes do not result in spillover infections in humans.

Scientists are still investigating the origins of the new coronavirus. Genetic similarities between the new human coronavirus and some of the coronaviruses found in bats indicate that the current pandemic was caused by a spillover infection from bats to people, either directly or viapangolins or another intermediate host.

8. People in the US usually do not come in contact with bats or pangolins. How could a virus that originated in these animals infect so many people in the US?

You have seen how the new coronavirus in humans probably evolved from a coronavirus in bats by mutation and natural selection. Some people have proposed an alternative hypothesis, that scientists used genetic engineering to produce the new coronavirus in a laboratory.

9. Complete the last two columns of this table to evaluate whether the molecular evidence supports the genetic engineering hypothesis.

If scientists were using genetic engineering to make a coronavirus that would cause a pandemic, they probably would have:

Circle the letter for the most relevant evidence from the list below.

Does this evidence support the genetic engineering hypothesis?

started with a coronavirus known to infect humans a or b Yes ___ No ___

used computer simulations to predict which mutations in the spike protein gene would improve binding of the spike protein to molecules on the surface of human cells

a or b Yes ___ No ___

a. The genes in the RNA of the coronavirus that causes COVID-19 are less like the genes in the RNA of other coronaviruses that infect humans and more like the genes in the RNA of some coronaviruses that infect bats and pangolins.

b. The available computer simulations were inaccurate, so they did not predict any advantage for the mutations observed in the spike protein gene of the coronavirus that caused the COVID-19 pandemic.

3

How has the new coronavirus changed during the COVID-19 pandemic?

10. The G mutation in the gene for the spike protein was present in less than 10% of the samples of coronaviruses taken from infected people in January 2020. By June 2020, almost all the coronavirus samples had the G mutation. Suggest a hypothesis to explain why the G mutation became so common.

To better understand what happened, consider the figure below which shows the spread of coronavirus infections if we make the following assumptions. Each person infected with the original version of the coronavirus (O) transmits the infection to

one other person. Each person infected with coronaviruses that have the hypothetical T mutation transmits the

infection to two other people. Thus, the T mutation doubles the rate of transmission.The table on the right shows the increase in the percent of infected people who have coronaviruses with the T mutation.

The actual G mutation in the spike protein gene increases the rate of transmission of coronavirus infections by about 20%. The changed amino acid in the G version of the spike protein allows the coronavirus to enter human cells more easily.

11. Based on this information, explain why the G mutation became so common.

4

You may have heard of the new variants or strains of coronavirus that have become common in several different countries. Each of these variants has several mutations in different parts of the gene for the spike protein, as well as mutations in other coronavirus genes.

12. The coronavirus variant that was first identified in South Africa was extremely rare in September 2020, but four months later this variant was responsible for almost all the coronavirus infections in South Africa. Propose a hypothesis to explain why this variant became so common in South Africa. Your hypothesis should be specific about the effects of the mutations in the spike protein gene and the role of natural selection.

13. Watch the video, “How – and why – coronaviruses mutate” (https://www.statnews.com/2021/01/14/how-coronavirus-mutates/). Use the information in the video to revise and add to your explanation of the spread of the variant in South Africa.

In addition to the coronavirus variant in South Africa, a second variant has become common in Brazil, and a third variant has become common in the UK. These three coronavirus variants originated independently and are not descended from each other. However, all three of these variants have the same mutation that increases transmission of the coronavirus from person to person. In addition, both the South African and Brazilian variants have the same two mutations that decrease the effectiveness of immune defenses developed in response to a previous coronavirus infection or vaccination.

14. Propose a hypothesis to explain why the same mutations are found in the coronavirus variants that have become common in three different parts of the world.

All three of these coronavirus variants have been found in the US. Scientists predict that the variant that was first detected in the UK will become the most common type of coronavirus in the US by May 2021. In the UK, the spread of this more contagious variant contributed to an increase in the number of cases, hospitalizations, and deaths. However, this increase was reversed by strict limitations on indoor, in-person social interactions, together with requirements for physical distancing and use of masks, plus a vigorous vaccination campaign.

15. When many people are infected with the new coronavirus, this provides lots of opportunities for coronavirus mutations and natural selection. What policies could minimize the likelihood that new, more contagious and dangerous coronavirus variants will emerge in the coming months?

5