coronavirus evolution TN
Teacher Notes for “Coronavirus Evolution and the COVID-19
Pandemic”[footnoteRef:1] [1: By Dr. Ingrid Waldron, Department of
Biology, University of Pennsylvania, 2021. These Teacher Notes and
the related Student Handout are available at
https://serendipstudio.org/exchange/bioactivities/coronavirusOrigin.
]
To begin this analysis and discussion activity, students explore
two hypotheses about the origins of the new coronavirus that is
causing the COVID-19 pandemic. First, students learn how mutations
and natural selection can produce a spillover infection. Then,
students use molecular evidence to evaluate the hypothesis that
scientists used genetic engineering to produce the new coronavirus.
Next, students analyze the contributions of mutation and natural
selection to the development of the new coronavirus variants that
are more contagious and/or can evade immune defenses. Finally,
students propose policies to reduce the risk that even more
dangerous variants could develop in the future.
You could use this activity to introduce coronaviruses and
natural selection. However, some students may find it helpful to
complete the following analysis and discussion activities before
they begin this activity.
· “Coronaviruses – What They Are and How They Can Make You Sick”
(includes an introduction to how coronaviruses replicate)
(https://serendipstudio.org/exchange/bioactivities/coronavirusintro)
· “What is natural selection?”
(https://serendipstudio.org/exchange/bioactivities/NaturalSelectionIntro).
If your students would benefit from an introduction to or a
review of how RNA provides the instructions to make proteins, I
recommend:
· the 5-minute video, “What Is DNA and How Does It Work?”
(https://www.statedclearly.com/videos/what-is-dna/) or
· the analysis and discussion activity, “How Genes Can Cause
Disease – Understanding Transcription and Translation”
(https://serendipstudio.org/exchange/bioactivities/trans).
Learning Goals
In accord with the Next Generation Science Standards
(NGSS)[footnoteRef:2]: [2: Quotations are from
http://www.nextgenscience.org/sites/default/files/HS%20LS%20topics%20combined%206.13.13.pdf
]
· This activity helps students to prepare for Performance
Expectation HS-LS4-3. “Apply concepts of statistics and probability
to support explanations that organisms with an advantageous
heritable trait tend to increase in proportion to organisms lacking
this trait.”
· This activity helps students to understand the Disciplinary
Core Ideas:
· LS4.B “Natural selection occurs only if there is both (1)
variation in the genetic information between organisms in a
population and (2) variation in the expression of that genetic
information – that is, trait variation – that leads to differences
in performance among individuals. The traits that positively affect
survival are more likely to be reproduced, and thus are more common
in the population. The traits that positively affect survival are
more likely to be reproduced, and thus are more common in the
population.”
· LS4.C “Natural selection leads to adaptation, that is, to a
population dominated by organisms that are… well suited to survive
and reproduce in a specific environment. That is, the differential
survival and reproduction of organisms in a population that have an
advantageous heritable trait leads to an increase in the proportion
of individuals in future generations that have the trait into a
decrease in the proportion of individuals that do not.”
· Students engage in the Scientific Practices:
· “Constructing Explanations. Apply scientific ideas, principles
and/or evidence to provide an explanation of phenomena and solve
design problems…”
· “Developing and Using Models. Develop and/or use a model
(including mathematical and computational) to generate data to
support explanations, predict phenomena, analyze systems, and/or
solve problems.”
· This activity helps students to understand the Crosscutting
Concept, “Stability and Change. Much of science deals with
constructing explanations of how things change and how they remain
stable.”
Instructional Suggestions and Biology Background
If your students are learning online, we recommend that they use
the Google Doc version of the Student Handout available at
https://serendipstudio.org/exchange/bioactivities/coronavirusOrigin.
To answer questions 2a, 4 and 6, students can either print the
relevant pages, draw on them and send pictures to you, or they will
need to know how to modify a drawing online. To answer online, they
can double-click on the relevant drawing in the Google Doc to open
a drawing window. Then, they can use the editing tools to answer
the questions.[footnoteRef:3] You may want to revise the GoogleDoc
or Word document to prepare a version of the Student Handout that
will be more suitable for your students; if you do this, please
check the format by viewing the PDF. [3: To draw a shapeAt the top
of the page, find and click Shape.Choose the shape you want to
use.Click and drag on the canvas to draw your shape.To insert
textAt the top of the page, click Insert.To place text inside
a box or confined area, click Text Box and drag it to
where you want it.Type your text.You can select, resize and format
the word art or text box, or apply styles like bold or italics to
the text.When you are done, click Save and Close.]
To maximize student participation and learning, I suggest that
you have your students work individually or in pairs to complete
each group of related questions and then have a class discussion
after each group of questions. In each discussion, you can probe
student thinking and help them develop a sound understanding of the
concepts and information covered before moving on to the next group
of related questions.
A key is available upon request to Ingrid Waldron
([email protected]). The following paragraphs provide additional
instructional suggestions and background information – some for
inclusion in your class discussions and some to provide you with
relevant background that may be useful for your understanding
and/or for responding to student questions.
Where did the new coronavirus come from?
The novel coronavirus that is causing the current global
pandemic is called SARS-CoV-2 because of its similarity to
SARS-CoV, the coronavirus which caused an earlier, smaller outbreak
of SARS = Severe Acute Respiratory Syndrome (mainly in Asia in
2002-2004). The disease caused by SARS-Cov-2 is called COVID-19.
(CO stands for corona, VI stands for virus and D stands for
disease; 19 stands for 2019, the year in which this disease was
first identified.) As of February 27, 2021, the estimated number of
COVID-19 deaths was 510,000 in the US and 2.5 million in the world
(https://www.google.com/search?q=Estimated+deaths+worldwide+Covid+19&rlz=1C1GCEA_enUS862US862&oq=Estimated+deaths+worldwide+Covid+19&aqs=chrome..69i57.4118j0j7&sourceid=chrome&ie=UTF-8).
Question 1 should get students thinking about the driving
question for this part of the activity. A class discussion of
student answers will help you to understand their current
knowledge, including any misconceptions they may have.
The recommended 9-minute video, “Where do new viruses come
from?” (https://www.youtube.com/watch?v=NJLXdsO1GBI) is generally
very accurate, but at one point the narrator incorrectly refers to
the virus, rather than the disease, as COVID-19. As explained in
the video, spillover infections (the transmission of a pathogen
from one animal to another) have been responsible for multiple
human diseases caused by viral infections, including HIV (human
immunodeficiency virus), Ebola virus, West Nile virus, Zika virus,
influenza A virus (H1N1), Middle East respiratory syndrome
coronavirus (MERS-CoV), and the first SARS outbreak (SARS-CoV).
Spillover infections are also called zoonotic diseases.
The coronavirus spike protein binds to a molecular receptor on
the surface of cells in the nose, lungs, and multiple other parts
of the body. This binding causes the spike protein to change shape
in a way that draws the virus toward the cell so the viral envelope
merges with the cell membrane; this allows the viral RNA to enter
the cell. Coronavirus RNA serves as mRNA and the cell’s ribosomes
translate the viral RNA to make viral proteins. The viral RNA is
copied by a viral enzyme, RNA-dependent RNA polymerase (replicase
in the figure below). The viral proteins and RNA assemble to form
new viruses that are released from the infected cell, which
typically dies. The viruses that are released can infect other body
cells; they may be inactivated by the person’s immune system; or
they can be spread by coughing, sneezing, shouting, singing, and
breathing where they may infect other people.
(https://www.ncbi.nlm.nih.gov/books/NBK554776/bin/Covid__Replication.jpg)
The descriptions on page 2 of the Student Handout, together with
questions 5-6, provide a simplified introduction to how mutation
and natural selection contribute to spillover infections. It is
unlikely that a single mutation would have such a dramatic effect
as the H mutation in this hypothetical example. Instead, multiple
rounds of more modest mutations and natural selection are probably
required for most spillover events.
Mutations are caused by random errors in copying the viral
RNA.[footnoteRef:4] Since the viral RNA comes from a virus that has
been successful in infecting a cell and reproducing, most mutations
will either have little or no effect on fitness or will reduce the
fitness of the virus (corresponding to the N mutation in this
hypothetical example). Even if a mutation results in a virus that
can bind to molecules on the surface of the cells of a new host and
the mutated virus comes in contact with the new host, the virus
will need additional adaptations to be efficiently reproduced by
the cells of the new host. This will only occur if random mutations
provide the needed raw material and natural selection is able to
accumulate genetic changes that result in a virus that is well
adapted to reproduction inside the new host. Natural selection will
also favor any mutations that contribute to the coronavirus’
ability to spread from person to person. Students may need to be
reminded that mutation is random, but natural selection is not
random. [4: The analysis and discussion activity, “How Genes Can
Cause Disease – Understanding Transcription and Translation”
(https://serendipstudio.org/exchange/bioactivities/trans), includes
the example of a mutation that changes a single amino acid in the
hemoglobin protein to cause sickle cell anemia. Another activity,
"Mutations and Muscular Dystrophy"
(https://serendipstudio.org/exchange/bioactivities/mutation),
includes examples of additional types of mutation, including some
mutations that have major effects on the dystrophin protein and
some that have no effect on the amino acid sequence in the
protein.]
As discussed on the top of page 3 of the Student Handout and in
question 7, viral mutations are common, but most mutations do not
result in spillover infections to humans. Spillover infections
require the combination of an initial mutation that allows a virus
to infect a human cell, contact between animal and human that
allows the mutated virus to reach a human host, and subsequent
mutations and natural selection that allow the virus to spread
among humans. The history of spillover infections provides evidence
that this rare combination of events has repeatedly occurred in the
past, which is understandable when you consider the trillions of
animal viruses and billions of people in the world
(https://www.nationalgeographic.com/science/2020/04/factors-allow-viruses-infect-humans-coronavirus/).
The Student Handout does not discuss another source of genetic
variation, called recombination. When two genetically different
coronaviruses infect the same cell, recombination can combine parts
of the RNA from these two coronaviruses to produce a coronavirus
with a new combination of mutations. After more than a decade of
research on the origins of the 2002-2004 SARS outbreak, scientists
identified a cave where many horseshoe bats roosted; the
coronaviruses that infected these bats had RNA segments that were
very similar to RNA segments in the coronavirus that caused this
SARS outbreak. These scientists found evidence of frequent
recombination of RNA segments from different coronaviruses, and
they have argued that recombination in bat coronaviruses probably
contributed to the origin of the SARS-CoV virus that caused the
2002-2004 SARS outbreak
(https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006698).
Additional evidence indicates that this bat coronavirus caused a
spillover infection in civets which caused the spillover infection
in humans.
Question 8 (and the introductory video) may prompt students to
inquire about the effectiveness of travel restrictions to stop or
slow the spread of COVID-19 and similar pandemics. The available
evidence suggests that border closings can effectively reduce
infection rates, but only if they are begun promptly when a new
coronavirus emerges and if they are combined with other measures
such as testing for infections, contact tracing, and strict
quarantine of arriving travelers and any infected individuals
(https://www.cochrane.org/CD013717/PUBHLTH_can-travel-related-control-measures-contain-spread-covid-19-pandemic;
https://www.nature.com/articles/d41586-020-03605-6).
One way that people are exposed to bat coronaviruses is that
children or adults may enter bat roosting sites where they may
breathe in dust with coronaviruses from bat guano and urine. People
are exposed to pangolin coronaviruses when pangolins are illegally
sold for meat or use in traditional medicine.
The evidence that is presented on the bottom half of page 3 of
the Student Handout is derived from “The proximal origin of
SARS-CoV-2” (https://www.nature.com/articles/s41591-020-0820-9).
This evidence provides the basis for a strong argument against the
hypothesis that scientists purposely developed SARS-CoV-2 to cause
a pandemic. However, this evidence is less persuasive against the
hypothesis that SARS-CoV-2 resulted from an accidental release from
a laboratory that was doing research on bat coronaviruses.
(https://www.nytimes.com/2021/03/04/health/covid-virus-origins.html;
https://www.washingtonpost.com/world/asia_pacific/coronavirus-who-china-investigation-wuhan/2021/02/09/2af3c44c-6a79-11eb-a66e-e27046e9e898_story.html;
https://www.sciencemag.org/news/2020/07/trump-owes-us-apology-chinese-scientist-center-covid-19-origin-theories-speaks-out;
https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q%26A.pdf)
In summary, the weight of the evidence indicates that SARS-CoV-2
arose through mutation, recombination, and natural selection of
coronaviruses that originated in bats
(https://advances.sciencemag.org/content/6/27/eabb9153;
https://www.cell.com/trends/ecology-evolution/fulltext/S0169-5347(20)30348-7).
However, many specifics are currently unknown. To gain more
information about the origin of SARS-CoV-2, scientists will
continue to:
· study coronaviruses in bats, pangolins, and other possible
intermediate hosts
· search for more information about the earliest human COVID-19
infections.
It would also be helpful to have more information about the
types of coronavirus research at the Wuhan Institute of
Virology.[footnoteRef:5]
(https://www.nature.com/articles/d41586-021-00502-4;
https://www.nature.com/articles/d41586-020-01541-z;
https://www.nytimes.com/2020/07/08/health/coronavirus-origin-china-lucey.html)
[5: Notice that scientists have identified the probable origin of
SARS-CoV, but there is much more uncertainty about the origin of
SARS-CoV-2. This illustrates the Nature of Science principles that
science is a process that takes time and scientific findings may
have varying degrees of certainty and uncertainty. If you want more
information on this research, I recommend “How China’s ‘Bat Woman’
Hunted down Viruses from SARS to the New Coronavirus”
(https://www.scientificamerican.com/article/how-chinas-bat-woman-hunted-down-viruses-from-sars-to-the-new-coronavirus1/).]
You may want to add the following question to page 3 of the
Student Handout.
Researchers have made several recommendations for preventing new
spillover infections in humans. These recommendations include:
· Reduce human contact with wild animals.
· Regularly test the blood of people who are exposed to viruses
in bats or other animals to detect exposure to any new or unusual
viruses and take prompt action to prevent spread of these
viruses.
· Monitor hospital patients to detect clusters of cases with
unusual symptoms that may indicate a new spillover infection and
act promptly to prevent wider spread of any new infectious
disease.
What are the pros and cons of these recommendations?
The strategies recommended in this question would reduce the
likelihood of a future pandemic. However, these strategies would
require a substantial investment of resources. Also, past
experience suggests that many people may be reluctant to comply
with the recommended behavioral changes.
How has the coronavirus changed during the COVID-19
pandemic?
Many of the estimated 113 million known cases of COVID-19 have
been confirmed by testing for coronavirus RNA in a sample collected
from the nose (or saliva). For some of these samples, scientists
have checked the sequence of the nearly 30,000 nucleotides in the
RNA of the coronavirus. Scientists have found lots of variation in
the nucleotide sequence, but research has focused on a relatively
small number of mutations that have become widespread. Mutations
refer to changes in the nucleotide sequence relative to the
original strain of coronavirus that spread around the world in late
2019 and very early 2020.
Page 4 of the Student Handout analyzes how one mutation spread
worldwide in the first half of 2020. The graph of the spread of the
G mutation in question 10 is based on sequencing 52,292 samples
worldwide during the first half of 2020
(https://media.nature.com/original/magazine-assets/d41586-020-02544-6/d41586-020-02544-6.pdf).
The scientific name of the G mutation is D614G because it results
in the amino acid glycine (G) instead of aspartic acid (D) in the
614th amino acid position of the spike protein. Molecular evidence,
cell experiments, and epidemiological evidence indicate that this
mutation makes it easier for the coronavirus to enter respiratory
system cells and thus increases the transmission of coronaviruses
from person to person.
The figure in the bottom half of page 4 of the Student Handout
shows an unrealistically regular spread of coronavirus infections.
The actual spread of coronavirus infections shows much more
variation. On the one hand, many infected people don’t pass their
coronavirus infection to anyone else. At the other extreme,
superspreader events, where a single infected person infects many
other people, have played a significant role in the spread of
coronavirus infections
(https://www.nature.com/articles/d41586-021-00460-x). Notice that
natural selection favors mutations that increase reproduction as
well as mutations that decrease mortality.
The last page of the Student Handout focuses on three variants
that have caused the most concern in January and February 2021
(https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html).
A variant is a group of viruses that share the same set of
inherited mutations and have become relatively common in a region
or country.
The figure below shows the spread of the B.1.351 variant (also
called 20H/501Y.V.2) in South Africa. This variant has eight
mutations in the spike protein gene, including:
· N501Y, which helps to make this variant more contagious,
and
· E484K and K417N, which decrease the effectiveness of immune
defenses that developed after an initial infection with the
original strain or after vaccination with a vaccine developed
against the original strain.
(https://www.livescience.com/south-african-coronavirus-variant-faq.html;
https://www.washingtonpost.com/health/2021/02/05/virus-variant-reinfection-south-africa/)
(The Y axis extends from 0% to 100% of the samples of
coronavirus, and the different colors correspond to different
variants;
https://nextstrain.org/ncov/global?f_country=South%20Africa)
The variant that was first detected in Brazil (P.1) has 21
mutations, including at least three that were observed in the
variant that was first detected in South Africa (N501Y, E484K and
K417N/T). These mutations increased the rate of transmission of
coronavirus infections and decreased the effectiveness of immune
defenses developed during earlier infections. Because immune
defenses were less effective against the P.1 variant, this variant
was able to infect individuals who had already been infected once;
this characteristic was particularly favored by natural selection
in the city of Manaus where roughly three-quarters of the residents
had already had COVID-19 by October 2020. In Manaus, the P.1
variant increased from 0% to 87% of coronavirus samples in just
eight weeks. Scientists have estimated that the P.1 variant is
1.4-2.2 times more transmissible than the previously circulating
form of the virus.
(https://www.nytimes.com/2021/03/01/health/covid-19-coronavirus-brazil-variant.html)
The variant that was first detected in the UK (B.1.1.7) has
multiple mutations, including the N501Y mutation found in the
variants first detected in South Africa and Brazil. Also, the E484K
mutation has recently been found in some cases of the UK variant
(https://www.newscientist.com/article/2266429-uk-coronavirus-variant-gets-nastier-as-south-african-variant-spreads/;
https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm). The fact that
the same mutations are found in variants that developed
independently indicates that natural selection favors coronavirus
variants that have these mutations, e.g., because they increase
transmission and/or decrease the effectiveness of immune defenses.
This is an example of convergent evolution, a more general
phenomenon that has occurred frequently; a familiar example is the
wide, thin shape of the wings of birds, bats and insects.
Recent evidence indicates that the variant first detected in the
UK increases the risk of dying of COVID-19 in two ways:
· The risk of infection is increased because the rate of
transmission of coronavirus infections is increased by roughly 50%
for this variant.
· The risk that a coronavirus infection will result in death
appears to be ~30-50% higher for this variant.
(https://www.nature.com/articles/d41586-021-00299-2)
This more transmissible coronavirus variant is currently
spreading rapidly in the US
(https://www.nytimes.com/interactive/2021/03/06/us/coronavirus-variant-sequencing.html;
https://www.washingtonpost.com/health/ukvariant-coronavirus-us-spread/2021/02/07/a197dbc2-680a-11eb-8468-21bc48f07fe5_story.html).
The figure below shows that the number of coronavirus infections in
the UK increased during December as this variant was spreading
widely. Although this more contagious variant continued to spread
in the UK in January, there was a sharp decrease in cases after the
UK government carried out a vigorous vaccination campaign and
instituted stricter limitations on when and how people could leave
home and interact in person with people outside their household
(https://www.gov.uk/guidance/national-lockdown-stay-at-home). The
increase and subsequent decrease in cases was also influenced by
holiday travel and get-togethers.
(https://www.worldometers.info/coronavirus/country/uk/)
Multiple additional mutations and variants have been observed
and are expected in the future as the coronavirus continues to
evolve. For example, a variant that appears to be more
transmissible has been spreading widely in California
(https://www.nytimes.com/2021/02/23/health/coronavirus-california-variant.html).
The emergence of new mutations and variants has been facilitated
by the very large number of coronavirus infections and two
additional factors. When a substantial part of the population has
already been infected with the original strain or vaccinated
against the original strain, then the ability to evade immune
defenses against the original strain has a bigger selective
advantage. Also, it appears that new variants with multiple
mutations may evolve during prolonged coronavirus infections in an
immunocompromised individual who has been treated with antibodies
from the blood of people who have recovered from coronavirus
infections.
Follow-Up Activities and Additional Resources
COVID-19 Vaccines – How do they work?
https://serendipstudio.org/exchange/bioactivities/coronavirusvaccine
Students begin by proposing a hypothesis to explain why most
people who have had COVID-19 or have been vaccinated do not become
sick if they are exposed to the coronavirus in the future. Students
analyze how the adaptive immune system responds to a coronavirus
infection and how this response differs after a first vs. second
exposure to coronavirus. Then, students analyze the body’s
responses to an RNA vaccine and revise their hypothesis about how a
vaccine protects against illness. Finally, students use reliable
sources to investigate their questions about COVID-19 vaccines.
Resources for Teaching about Coronavirus
https://serendipstudio.org/exchange/bioactivities/coronavirus
This webpage has compiled information about learning activities
and other resources for teaching high school biology students about
the coronavirus and COVID-19.
If your students have additional questions about the novel
coronavirus and the COVID-19 pandemic, you may want to encourage
them to research these questions using the following sources of
reliable information.
· Coronavirus
(COVID-19) (https://www.cdc.gov/coronavirus/2019-ncov/index.html)
· Science
(https://www.sciencenews.org/editors-picks/2019-novel-coronavirus-outbreak)
· New York Times
(https://www.nytimes.com/news-event/coronavirus)
· FAS COVID-19 – Ask a Scientist (https://covid19.fas.org/)
For additional information and learning activities about natural
selection, see “Resources for Teaching and Learning about
Evolution”
(https://serendipstudio.org/exchange/bioactivities/evolrec).
Sources for Student Handout Figure
· Figure of coronavirus structure, adapted from
https://viralzone.expasy.org/resources/nCoV_SARS_virion.png
· Figure of translation and mutation, adapted from
https://i.pinimg.com/564x/1d/6b/e9/1d6be9580a00ace750b472953a2bd77f--point-mutation-ap-biology.jpg
· Figure of bat, pangolin and humans, adapted from
https://news.cgtn.com/news/7a416a4d3245444f7763444f3163544e7951444f31457a6333566d54/img/2884c659bdd747f9b3374d9d6e76988d/2884c659bdd747f9b3374d9d6e76988d.jpeg
· Figure of trends in G mutation, adapted from
https://www.nature.com/articles/d41586-020-02544-6
Other figures were made by the author.
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