The Coronavirus Genome

The coronavirus is an oily membrane packed with genetic instructions to make millions of copies of itself. The instructions are encoded in 30,000 letters of RNA a, c, g and u which the infected cell reads and translates into many kinds of virus proteins.

RNA instructions to make the ORF1a protein

Start of coronavirus genome

Start of coronavirus genome

Start of the

coronavirus

genome

Start of the

coronavirus

genome

In December, a cluster of mysterious pneumonia cases appeared around a seafood market in Wuhan, China. In early January, researchers sequenced the first genome of a new coronavirus, which they isolated from a man who worked at the market. That first genome became the baseline for scientists to track the SARS-CoV-2 virus as it spreads around the world.

Genome Wuhan-Hu-1, collected on Dec. 26 from an early patient in Wuhan

Genome Wuhan-Hu-1, collected on Dec. 26 from an early patient in Wuhan

Genome Wuhan-Hu-1, collected on Dec. 26 from an early patient in Wuhan

Genome Wuhan-Hu-1, collected on Dec. 26 from an early patient in Wuhan

A cell infected by a coronavirus releases millions of new viruses, all carrying copies of the original genome. As the cell copies that genome, it sometimes makes mistakes, usually just a single wrong letter. These typos are called mutations. As coronaviruses spread from person to person, they randomly accumulate more mutations.

The genome below came from another early patient in Wuhan and was identical to the first case, except for one mutation. The 186th letter of RNA was u instead of c.

Genome WH-09, collected on Jan. 8 from another patient in Wuhan

186th RNA letter changed

Genome WH-09, collected on Jan. 8 from another patient in Wuhan

186th RNA letter changed

Genome WH-09, collected on Jan. 8 from another patient in Wuhan

186th

RNA letter

changed:

Genome WH-09, collected on Jan. 8 from another patient in Wuhan

186th RNA letter

changed:

When researchers compared several genomes from the Wuhan cluster of cases they found only a few new mutations, suggesting that the different genomes descended from a recent common ancestor. Viruses accumulate new mutations at a roughly regular rate, so the scientists were able to estimate that the origin of the outbreak was in China sometime around November 2019.

Outside of Wuhan, that same mutation in the 186th letter of RNA has been found in only one other sample, which was collected seven weeks later and 600 miles south in Guangzhou, China. The Guangzhou sample might be a direct descendent of the first Wuhan sample. Or they might be viral cousins, sharing a common ancestor.

During those seven weeks, the Guangzhou lineage jumped from person to person and went through several generations of new viruses. And along the way, it developed two new mutations: Two more letters of RNA changed to u.

Genome GZMU0030, collected on Feb. 27 in Guangzhou

Another RNA letter mutated

This mutation also changed an amino acid

Genome GZMU0030, collected on Feb. 27 in Guangzhou

Another RNA letter mutated

This mutation also changed an amino acid

Genome GZMU0030, collected on Feb. 27 in Guangzhou

Another RNA letter mutated. This mutation also changed an amino acid.

Genome GZMU0030, collected on Feb. 27 in Guangzhou

Another RNA letter mutated. This mutation also changed an amino acid.

Mutations will often change a gene without changing the protein it encodes.

Proteins are long chains of amino acids folded into different shapes. Each amino acid is encoded by three genetic letters, but in many cases a mutation to the third letter of a trio will still encode the same amino acid. These so-called silent mutations dont change the resulting protein.

Non-silent mutations do change a proteins sequence, and the Guangzhou sample of the coronavirus acquired two non-silent mutations.

Amino acid change in the ORF1a protein

Amino acid change in the E protein

Amino acid change in ORF1a

Amino acid change in E

Amino acid change in the E protein

Amino acid change in the ORF1a protein

Amino acid change in the E protein

Amino acid change in the ORF1a protein

But proteins can be made of hundreds or thousands of amino acids. Changing a single amino acid often has no noticeable effect on their shape or how they work.

As the months have passed, parts of the coronavirus genome have gained many mutations. Others have gained few, or none at all. This striking variation may hold important clues to coronavirus biology.

The parts of the genome that have accumulated many mutations are more flexible. They can tolerate changes to their genetic sequence without causing harm to the virus. The parts with few mutations are more brittle. Mutations in those parts may destroy the coronavirus by causing catastrophic changes to its proteins. Those essential regions may be especially good targets for attacking the virus with antiviral drugs.

Total number of amino acid substitutions found in 4,400 coronavirus genomes from Dec. to April

Longer lines may show places where the genome is more tolerant of mutations.

Gaps may show critical spots in the genome that cannot tolerate mutations.

Total number of amino acid changes in 4,400 coronavirus genomes from Dec. to April

Longer lines may show places where the genome is more tolerant of mutations.

Gaps may show critical spots in the genome that cannot tolerate mutations.

Total number of amino acid changes in 4,400 coronavirus genomes from Dec. to April

Longer lines may show places where the genome is more tolerant of mutations.

Gaps may show critical spots in the genome that cannot tolerate mutations.

Total number of amino acid changes in 4,400 coronavirus genomes from Dec. to April

Longer lines may show places where the genome is more tolerant of mutations.

Gaps may show critical spots in the genome that cannot tolerate mutations.

As mutations accumulate in coronavirus genomes, they allow scientists to track the spread of Covid-19 around the world.

On January 15, a man flew home to the Seattle area after visiting family in Wuhan. After a few days of mild symptoms he tested positive for Covid-19. He became the first confirmed case of Covid-19 in the United States.

An X-ray of the patients lungs showed evidence of pneumonia.NEJM

The genome of his virus contained three single-letter mutations also found in viruses in China. They allowed scientists to trace the mans infection to its source.

Genome WA1, collected on Jan. 19 from a man in the Seattle area who visited Wuhan

Genome WA1, collected on Jan. 19 from a man in the Seattle area who visited Wuhan

Genome WA1, collected on Jan. 19 from a man in the Seattle area who visited Wuhan

Genome WA1, collected on Jan. 19 from a man in the Seattle area who visited Wuhan

Identical genomes collected on Jan. 21 in Fujian and Guangdong provinces

Identical genomes collected on Jan. 21 in Fujian and Guangdong provinces

Identical genomes collected on Jan. 21 in Fujian and Guangdong provinces

Identical genomes collected on Jan. 21 in Fujian and Guangdong provinces

Five weeks later, a high school student in Snohomish County, Wash., developed flu-like symptoms. A nose swab revealed he had Covid-19. Scientists sequenced the genome of his coronavirus sample and found it shared the same distinctive mutations found in the first case in Washington, but also bore three additional mutations.

Genome WA2, collected on Feb. 24 from a high-school student in the Seattle area

Genome WA2, collected on Feb. 24 from a high-school student in the Seattle area

Genome WA2, collected on Feb. 24 from a high-school student in the Seattle area

Genome WA2, collected on Feb. 24 from a high-school student in the Seattle area

That combination of old and new mutations suggested that the student did not acquire the coronavirus from someone who had recently arrived from another country. Instead, the coronavirus was probably circulating undetected in the Seattle area for about five weeks, since mid-January.

Since then, viruses with a genetic link to the Washington cluster have now appeared in at least 14 states and several countries around the world, as well as nine cases on the Grand Princess cruise ship.

Genome collected on March 5 from two passengers on the Grand Princess cruise ship

Genome collected on March 5 from two passengers on the Grand Princess cruise ship

Genome collected on March 5 from two passengers on the Grand Princess cruise ship

Genome collected on March 5 from two passengers on the Grand Princess cruise ship

A different version of the coronavirus was also secretly circulating in California. On Feb. 26, the C.D.C. announced that a patient in Solano County with no known ties to any previous case or overseas travel had tested positive.

A sample taken the next day revealed that the virus did not have the distinctive mutations found in Washington State. Instead, it only had a single mutation distinguishing it from the original Wuhan genome. That indicates that it got to California through a separate introduction from China.

Genome UC4, collected on Feb. 27 from a patient in Solano County, Calif.

Here is the original post:

How Coronavirus Mutates and Spreads - The New York Times