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Evolution of the virus responsible for Covid-19

Activity 1 – Evolution of the virus responsible for Covid-19 (SARS-Cov-2)


  1. Understand how evolutionary change occurs in viruses
  2. Understand the difference between synonymous and non-synonymous mutations
  3. Understand where SARS-CoV-2 originated, how it is related to viruses that have caused disease in humans [SARS and MERS], and how epidemiologists have hypothesized the origin of the novel coronavirus using phylogenetics
  4. Understand how mutations can be used to trace transmission of SARS-CoV-2 between hosts in humans
  5. Understand the spike protein and its role in entry into the host cell
  6. Understand the role of vaccines

Read: How Coronavirus Mutates and Spreads (NY Times)

Read: New coronavirus variant: what is the spike protein and why are mutations on it important? (


Phylogenetic network analysis of SARS-CoV-2 genomes

Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins


Currently, the global community is facing a pandemic (the virus responsible is SARS-CoV-2) which causes the disease Covid-19, which was named for the similarity of its structure to SARS (severe acute respiratory syndrome) related coronaviruses (coronaviruses are a group of related RNA viruses that have evolved in mammals and birds) (Fig. 1).

Researchers working in several different labs have recently confirmed the genetic similarity of SARS-CoV-2 and other betacorona viruses found in mammals such as bats using whole-genome sequencing and phylogenetics (Fig. 1). The whole-genome sequence of the SARS-CoV-2 virus has 96.2% similarity to that of a bat SARS-related coronavirus (SARSr-CoV; RaTG13); has a lower similarity to that of SARS-CoV (about 79%) or MERS-CoV (about 50%) (Fig 2).

Although the specific route of transmission from natural reservoirs such as bats is unclear, studies have identified that the betacorona virus found in bats is the most closely related virus to SARS-CoV-2.

Fig. 1. The evolution of coronaviruses (CoVs) isolated from bats, pangolins and humans

Fig. 2. The Evolution of coronaviruses (CoVs) that shows the evolutionary relationship of SARS-CoV-2 and SARS-CoV to viruses infecting bats and pangolins.

Origin of SARS-Cov-2

SARS-CoV-2 was detected in late December 2019 in Wuhan, the capital of central China’s Hubei Province, after a number of pneumonia cases appeared around a seafood market. At first, scientists suggested that SARS-CoV-2 was transmitted to humans by animals sold in the market. Since then, other hypotheses have emerged – another suggests that the market was the first site of human to human transmission and that the virus was transmitted to humans.

Since then the virus has rapidly spread across China and in other countries. As of September 3, 2021, 218,580,734 cases of SARS-CoV-2 infection have been confirmed worldwide, with 4,534,755 deaths (WHO). In the US, there have been more than 39,488,866 confirmed cases and 641,725 deaths (CDC) raising significant concerns about how to contain the transmission.

How does the virus evolve?

RNA viruses show extremely high mutation rates. Because of the lack of proofreading during replication, RNA viruses show the highest mutation rates among living organisms (RNA viruses mutation rate is dramatically high, up to a million times higher than that of their host).

Because of the high mutation rate, large population sizes, high replication rate and their short generation time, viral genomes are evolving rapidly (discussed also in Chapter 1 when we covered the evolution of HIV). The steady and predictable mutation rate and the use of phylogenetics (reconstructing evolutionary patterns by using trees) allows us to trace the transmission and probable routes of transmission of SARS-Cov-2.

Questions to be answered for the activity

Read How Coronavirus Mutates and Spreads in NY Times and use as a reference for this section.

  1. What factor(s) is/are responsible for the evolution of SARS-CoV-2? (What is the definition of evolution?) (Group 1)
  1. Do mutations always alter amino protein structure and function? What is meant by a “silent” mutation? Does a silent mutation change an amino acid in a protein sequence? Is a silent mutation a synonymous or nonsynonymous mutation? (Group 2)
  1. Which mutations (synonymous or nonsynonymous) are more common in the genome of SARS-CoV-2? (Group 3)
  1. In January, a man from the Seattle area came home after visiting China and later, was diagnosed with symptoms of Covid-19. The genome of SARS-Cov-2 was sequenced from a sample. Did his sample match a sample from China? (Group 4)
  1. Five weeks later after the first case in Washington, a high school student in WA was diagnosed with Covid-19 (and he had not traveled to China). The genome of SARS-Cov-2 was sequenced and three additional mutations were found. What conclusions could be drawn about the origination and transmission of SARS-Cov-2? (Group 5)
  1. Later, SARS-CoV-2 was identified from the first patient in CA. How did scientists trace the origination of the transmission? Was the genome of the virus identical to the genome of the virus collected in WA? Or China? Were the events linked (the virus was transmitted from WA to CA or was the virus transmitted from China to CA?) (Group 1)
  1. The first confirmed case of Covid-19 in New York was announced on March 1, after a woman living in Manhattan was infected while visiting Iran. What was the most common route of transmission of the virus in NY? How is this different than the west coast of the US? (Group 2)

8. What is the spike protein of SARS-CoV-2? How does the spike protein facilitate entry into the host cell? (Group 3)Use New coronavirus variant: what is the spike protein and why are mutations on it important? (

  1. Two of the vaccines that are distributed in the US (Pfizer and Moderna) are mRNA vaccines that provide protection against SARS-CoV-2. How is this achieved? (Group 4)
  1. The delta variant of SARS-Cov-2 circulating in the UK (and now if the US) could change the amino acid sequence of the spike protein and possibly altering? (Group 5)

Last Updated on September 5, 2021

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