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Central to Darwin's theory of evolution, the concept of "Tree of Life" is a metaphor illustrating the evolutionary relationships among different species. Of this tree, its branches depict speciation event, at which different species diverge from their most recent shared common ancester.
First, go to this webpage: https://www.ncbi.nlm.nih.gov/nuccore/NC_045512
This is the specific entry of the Coronavirus whole genome sequence in the NCBI's Nucleotide database. This database is a collection of sequences from all traditional divisions of biotechnology, including nucleotide sequences from all available public repositories.
Let's try to break down the information provided on this webpage:
Title: "Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome". This is like the title of a book, but instead of a book, it's the complete set of genetic instructions for the SARS-CoV-2 virus, the bad guy behind COVID-19. This particular 'copy' of the virus was isolated from Wuhan, where the virus was first identified.
NCBI Reference Sequence: "NC_045512.2". Think of this as the unique barcode or library call number for this specific virus genome. Just like how every book in a library has a unique call number, every sequence in this database has a unique identifier. You can use this number to find this exact sequence again in the future.
Reference: This section generally listed all the indexed publications that mention this particular entry. As you can see here, the first Coronavirus genome was sequenced, submitted and reported in January 2020.
Features: This section is like the index of a book. It points out important parts of the genetic sequence, like genes (pieces of the sequence that can be turned into proteins) and other significant features. It's like a roadmap to important landmarks in the sequence. We'll later delve into this section.
Sequence Information (ORIGIN): This is the heart of the page, the actual genetic sequence of the virus. It's like the text in a book, but instead of words and sentences, it's a long string of letters (A, T, G, C) that represent the building blocks of the virus's genetic material. This is the virus's 'instruction manual' that allows it to infect cells and replicate.
Related Information (on the right side of the page): This is like the "further reading" section you might find in a textbook. It provides links to related information like other scientific projects that are studying this virus, proteins that the virus produces, and scientific articles that have cited this sequence.
LinkOut to external resources (on the right side of the page): These are like footnotes that lead you to external resources for more information. They can take you to other databases or resources that can provide more context or tools for understanding this sequence.
Remember, this page is like a library book about one specific virus's genome. Just like how you can learn a lot about a topic by reading a book about it, scientists can learn a lot about this virus by studying its genome. And just like how a book is more than just its text (it also has a title, an index, footnotes, etc.), a genome is more than just its sequence. It's a complex, fascinating piece of biological data that scientists all over the world are studying to help fight diseases like COVID-19.
(You may skip this part in blue if you want)
Challenge: Even though viruses aren't considered "alive" in the traditional sense, and certainly aren't aware or conscious like we are, they've developed some pretty nifty strategies to survive and thrive. They've "evolved" these tricks over millions of years, not by going to virus school, but through nature's cutthroat cycle of trial and error. So, let's imagine for a moment - we're in a video game, and our characters aren't the usual heroes or adventurers, but viruses! Yep, you heard that right, we are viruses. The objective of this game isn't to defeat a dragon or save a kingdom, but to replicate ourselves as quickly and as abundantly as possible in a limited amount of time. The challenge is - we're not the only players in this game. It's filled with other viruses, each trying to outdo the others, in a changing environment. In this microscopic race against time, how would you make sure you stand out and win? There is not right or wrong answer here, just share your thoughts.
This is actually not a game to the viruses, but a live or death choice they have been facing for billions of years. The rate of virus replication is influenced by a variety of factors, including external ones, such as host availability, resource richness, temperature, pH, etc, as well as internal ones, such as genome size, mutation rate, life cycle, etc.
If you looked at the above webpage carefully, you may find that there two giant proteins (ORF1a and ORF1ab) generated from an overlapping region (ORF1ab: 266-21555, ORF1a: 266-13483). These giant proteins(also called polyproteins) are further cleaved into several proteins by proteases. So one RNA sequence could produce two polyproteins, this is achieved through a mechannism, called "Programmed ribosomal frameshifting", specifically -1 ribosomal frameshifting. This is a mechanism employed by many viruses to control the expression of their genes. It's difficult to pinpoint exactly when viruses "learned" this mechanism because it has likely been part of their evolution for millions or even billions of years.
The mechanism itself is a fascinating aspect of molecular biology. Essentially, while a virus's RNA is being translated by the host cell's ribosomes, the ribosomes are occasionally induced to shift backwards one nucleotide, causing them to read the RNA in a completely different "frame". This can result in the production of entirely different proteins than would be expected from the standard reading frame. It is a mechanism that viruses employ to maximize their coding capacity, and to finely control the production of various viral proteins.
In terms of evolution, it's likely that these kinds of sophisticated mechanisms arose through a long process of mutation and natural selection, just like other complex biological traits. Viruses that randomly acquired the ability to induce -1 frameshifting would have had an advantage in terms of their ability to evade the host's defenses and replicate more effectively, leading to these traits being passed on to subsequent generations of viruses.
Bear in mind that viruses are not conscious entities and do not "learn" in the way humans or other animals do. Rather, the characteristics of viruses are shaped by evolution, which involves random mutation and natural selection. If a particular mutation (like the ability to induce -1 frameshifting) increases a virus's ability to survive and reproduce, then that trait is more likely to become common in the population over time.
We know that proteins are composed of chains of amino acids. Their sequences are usually called the primary sequence of a protein. In the webpage above, let's get the amino acid sequences of both poly-proteins (ORF1a and ORF1ab), and look for similarities and differences between these two sequences. This process is called protein "alignment", and there are particular programs designed to do this kind of comparison (e.g., https://www.ebi.ac.uk/Tools/msa/clustalo/).
This is a section of the genetic sequence of the SARS-CoV-2 virus, specifically the part that codes for the spike glycoprotein. This is the protein that gives the virus its crown-like appearance and allows it to enter human cells.
Let's break it down:
gene 21563..25384 /gene="S" /locus_tag="GU280_gp02" /gene_synonym="spike glycoprotein" /db_xref="GeneID:43740568":
This tells us that the gene for the spike protein is located between positions 21563 and 25384 on the virus's genome. The gene is often referred to as "S" (short for spike), and it has a locus tag of "GU280_gp02", which is another way to identify it. The term "spike glycoprotein" is a synonym for this gene, and "GeneID:43740568" is its unique identifier in the database.
CDS 21563..25384:
CDS stands for "coding sequence". This is the part of the gene that is actually used to make the spike protein. It's also located between positions 21563 and 25384.
/note="structural protein; spike protein":
This is a note that the spike protein is a structural protein, meaning it's part of the physical structure of the virus.
/product="surface glycoprotein":
This tells us that the product of this gene (what it makes) is a surface glycoprotein. Glycoproteins are proteins that have sugars attached to them, and in this case, it's located on the surface of the virus.
/protein_id="YP_009724390.1" /db_xref="GeneID:43740568":
This is the unique identifier for the spike protein in the database.
/translation="MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFR...:
This is the actual sequence of amino acids that make up the spike protein. Each three-letter sequence of the virus's genetic material (its RNA) codes for a specific amino acid, and this is the sequence of those amino acids. Amino acids are the building blocks of proteins, so this is like the blueprint for the spike protein.
Similarly, you could get the sequence information for both the E and M proteins.
The sequences of S, E and M proteins are shown as in Fig.1 of Paper-I.
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