Analysis indicated the number of mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) doubles every 72 days.

As the coronavirus disease 2019 (COVID-19) pandemic continues infecting more people, SARS-CoV-2 is also evolving. Several new variants of the virus have now been discovered, some more infectious than the original strains. This suggests that the virus is already in an evolutionary race with its human hosts.

In a study published on the bioRxiv* preprint server, researchers have analyzed this evolution of the virus based on evolutionary ecology theory. Using the virus genomes available in the Global Initiative on Sharing Avian Influenza Data (GISAID) database, the researchers focused their inquiry on mutations in the receptor-binding domain (RBD) on the spike protein of SARS-CoV-2.

The team used their COVID-19 virus Mutation Tracking System, which tracks all mutations in a genome isolate. Using Monte Carlo simulations, they estimated the number of mutations per infected human

The total number of virus copies in the globe is a factor of the number of people infected and the number of copies produced per infected person. But, since testing does not uncover all the true infected cases, the researchers used a model that uses reported COVID-19 deaths to estimate the true number of worldwide infections. The model estimates by March 1, 2021, the number of infections is more than 384 million. Using this, they estimated about 10¹⁷ to 10²¹ copies of the virus were produced worldwide.

Analyzing RBD mutations

The number of RBD mutations increases with the number of virus copies produced, as every time there is transcription of the genome, there is a chance of mutations occurring. Analyzing the RBD variants detected so far, the team estimates a doubling time of the mutants to be about 72 days.

The RBD variants also have mutations in other parts of the viral genome, which leads to about 90,744 unique variants with at least one mutation in the RBD. However, the total number of SARS-CoV-2 variants is much higher as there are mutations also in regions other than the RBD.

Modeling suggested the detected RBD mutations are about 85% of the total variants, which may not be very accurate as it is based on the samples isolated, which could have a bias. Based on the model, it appears that one new mutation occurs for every 600,000 human infections.

Using an estimated 2 million daily infections as of February 15, 2021, this gives about three new effective variants produced every day.

Some of these variants, identified several months ago, are now being seen in the population in larger numbers. One of these successful variants is the B.1.1.7 strain. Here, a specific mutated amino acid seems to appear independently several times. This variant has diverged more and faster than others in the RBD region. In the evolutionary tree, the branch with this variant has led to heavy branches, with one of them diversifying quickly in the last months. In addition, the B.1.351 and P.1 variants are also being selected in the virus evolutionary tree.

Strong selection in SARS-CoV-2 mutations

Although the role of changes to biodiversity affecting the transmission of pathogens from animals to humans has been discussed, less attention has been paid to how a large globally connected human population is accelerating the evolution of SARS-CoV-2. With the number of unique RBD mutations doubling every 72 days, this speed risks outpacing human defenses.

Although the same variations could arise in independent locations, the SARS-CoV-2 evolutionary process is not random, and there is strong selection. These selection processes remove less infectious branches, and branches with more infectious strains become heavier. This is evidenced by the new strains B.1.1.7, B.1.351, and P.1, which appear to be more infectious than the original strain.

The presence of a huge number of available human hosts also allows for another mechanism of virus diversification, reassortment. This process involves an exchange of genetic segments among different virus segments that have infected the same cell, contributing to rapid diversification.

The analysis predicts more infective strains becoming dominant, accelerating the evolutionary rate of the virus, and challenging our ability to contain the pandemic. According to the Red Queen theory, we need to run faster just to keep pace with the virus, and even faster if we have to overcome it.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).