About Genome Sequencing

Context:

A recent study revealed that the rate of genetic changes in the monkeypox virus was higher than expected.

Relevance:

GS III- Science and Technology

Dimensions of the Article:

1. About Genome Sequencing: 
2. Importance of Genome Sequencing
3. Genomic surveillance
4. APOBEC3 protein
5. About Monkeypox

About Genome Sequencing: 

Genome sequencing is figuring out the order of DNA nucleotides, or bases, in a genome—the order of Adenine, Cytosine, Guanines, and Thymine that make up an organism’s DNA.

Human genome

• It is made up of 23 chromosome pairs with a total of about 3 billion DNA base pairs.
• There are 24 distinct human chromosomes: 22 autosomal chromosomes, plus the sex-determining X and Y chromosomes.
• Chromosomes 1-22 are numbered roughly in order of decreasing size.
• Somatic cells usually have one copy of chromosomes 1-22 from each parent, plus an X chromosome from the mother and either an X or Y chromosome from the father, for a total of 46.
• There are estimated 20,000-25,000 human protein-coding genes.
• The estimate of the number of human genes has been repeatedly revised down from initial predictions of 100,000 or more as genome sequence quality and gene finding methods have improved, and could continue to drop further.

Importance of Genome Sequencing

• Sequencing the genome is an important step towards understanding it.
• The genome sequence will represent a valuable shortcut, helping scientists find genes much more easily and quickly. A genome sequence does contain some clues about where genes are, even though scientists are just learning to interpret these clues.
• Scientists also hope that being able to study the entire genome sequence will help them understand how the genome as a whole works—how genes work together to direct the growth, development and maintenance of an entire organism.
• Finally, genes account for less than 25 percent of the DNA in the genome, and so knowing the entire genome sequence will help scientists study the parts of the genome outside the genes. This includes the regulatory regions that control how genes are turned on and off, as well as long stretches of “nonsense” or “junk” DNA—so called because significance of it hasn’t been established.

Genomic surveillance

• Genomic surveillance of pathogens could provide unique insights to understand the outbreak better, track the spread of pathogens and provide immense opportunities for public health decision-making as well as for epidemiology.
• Researchers from across the world have made available over 650 complete genome sequences of monkeypox isolates to date in public domain databases including GISAID and GenBank.
• This includes over 600 genomes which were sequenced this year alone from over 35 countries, including genomes of two isolates from India, collected from Kerala. 

Accelerated evolution of  monkeypox virus

• The monkeypox virus has a DNA genome of around 2,00,000 base pairs, roughly six times larger than that of SARS-CoV-2.
• Like other viruses, the monkeypox virus evolves by the accumulation of genetic errors, or mutations, in its genome when it replicates inside a host.
• Information about mutations occurring in different genome sequences of the monkeypox virus across different regions can, thus, provide essential insights into how the virus is evolving, its genetic diversity and other factors that may be relevant to the development of diagnostic tools.
• Being a DNA virus, the monkeypox virus like other poxviruses was believed to have a small rate of accumulating genetic changes compared to viruses with an RNA genome like SARS-CoV-2, which have a much larger rate of mutations.
• For poxviruses, this rate is estimated to be as low as a couple of genetic changes every year.
• A recent study, however, revealed that the observed rate of genetic changes in the virus was higher than expected — average of around 50 genetic changes.
• The higher-than-expected rate of evolution coupled with the rapid rise in monkeypox cases across the world could potentially be due to highly parallel evolution in a large number of individuals simultaneously, as the present outbreak came out of a superspreader event. 

APOBEC3 protein

• The study also suggests that several mutations that have been identified in the new sequences of the monkeypox virus may have emerged due to interaction between the virus genome and an important family of proteins coded by the human genome known as the Apolipoprotein B Editing Complex (or APOBEC3).
• These proteins offer protection against certain viral infections by editing the genome sequence of the virus while it replicates in the cell.
• Some researchers, therefore, suggest that many of the genetic mutations in the monkeypox genomes from the current outbreak are relics of the effect of APOBEC3 and may not provide a significant evolutionary advantage to the virus. 
• Monkeypox virus can infect a range of hosts, including non-human primates and rodents which could act as a natural reservoir. 
• Infections in the reservoir could also enable continued transmission and accumulation of mutations before spilling over to cause human infections. 
• Other studies have also suggested a continued evolution of the virus, including deletions involving genes as seen in a few genomes from the present outbreak, which could suggest newer ways in which the virus continues to evolve with sustained human-to-human transmission.

About Monkeypox:

• Monkeypox is a viral zoonotic disease with symptoms similar to smallpox, although with less clinical severity.
• The CDC’s monkeypox overview says the infection was first discovered in 1958 following two outbreaks of a pox-like disease in colonies of monkeys kept for research — which led to the name ‘monkeypox’.

Zoonotic disease

• Monkeypox is a zoonosis, that is, a disease that is transmitted from infected animals to humans.
• According to the WHO, cases occur close to tropical rainforests inhabited by animals that carry the virus.
• Monkeypox virus infection has been detected in squirrels, Gambian poached rats, dormice, and some species of monkeys.
• Human-to-human transmission is, however, limited — the longest documented chain of transmission is six generations, meaning the last person to be infected in this chain was six links away from the original sick person, the WHO says.

Transmission:

• Transmission, when it occurs, can be through contact with bodily fluids, lesions on the skin or on internal mucosal surfaces, such as in the mouth or throat, respiratory droplets and contaminated objects.

Symptoms

• According to the US Centers for Disease Control and Prevention (CDC), monkeypox begins with a fever, headache, muscle aches, back ache, and exhaustion.
• It also causes the lymph nodes to swell (lymphadenopathy), which smallpox does not.
• The WHO underlines that it is important to not confuse monkeypox with chickenpox, measles, bacterial skin infections, scabies, syphilis and medication-associated allergies.
• The incubation period (time from infection to symptoms) for monkeypox is usually 7-14 days but can range from 5-21 days.
• Usually within a day to 3 days of the onset of fever, the patient develops a rash that begins on the face and spreads to other parts of the body.
• The skin eruption stage can last between 2 and 4 weeks, during which the lesions harden and become painful, fill up first with a clear fluid and then pus, and then develop scabs or crusts.
• According to the WHO, the proportion of patients who die has varied between 0 and 11% in documented cases, and has been higher among young children.

-Source: The Hindu