What Biologists Do

SEQUENCING THINGS

nucleotide = a chemical molecule that is an important building block of DNA

DNA sequencing = measuring the order of nucleotides in DNA - check out some media on how this works

You only have to sequence one strand of DNA because of the specific structure of how the 2 strands of DNA attach to each other

DNA is the information that makes you, you.

Because of this, forensic scientists can use any sample someone might accidentally leave behind at a crime scene (skin, blood, etc) to extract DNA and identify who was there. 

Once you have extracted DNA you need to 'read' it to figure out whose it is. 

In order to understand how DNA is 'read', we need to zoom into the structure of DNA (post coming soon). We have all seen the twisted-looking shape of DNA, but if we unravel it and take a closer look, we can see that it looks a bit like a ladder. Each rung of the ladder is actually made of 2 bits stuck together. Each 'bit' or nucleotide is stuck to one of the 2 strands of the DNA; here they are coloured red and blue to make it clear. 

The red and the blue strands are not very exciting (they're identical for everybody), what is interesting is the order of nucleotidesIf you take another look at the ladder you can see that there are only 4 different types of nucleotide: A, T, C and G. Everybody has these 4 nucleotides, but what makes you unique is that in your DNA the order of nucleotides will be slightly different from every other person on the planet. When you hear the phrase 'DNA sequencing', what that means is reading the order of these nucleotides. 

Al and Bob are 2 different people, so their DNA will have a different order of nucleotides. If a scientists sequenced their DNA, they would find these results:

Al's DNA sequence:     ATGCGACT

Bob's DNA sequence:  ATCCGACT

Al and Bob's DNA here differ by one nucleotide. 

Although we are looking at just bits of DNA that are 8 nucleotides long here, remember that your DNA is actually 3 200 000 000 nucleotides long!

There are lots of different ways to actually sequence DNA. Frederik Sanger (1918-2013) helped invent one of the first ways to do it in 1977 - called Sanger Sequencing. Since the 80s new technologies to sequence DNA have become much faster and cheaper, which is important if you think about how much DNA we have to sequence!

DNA is not the only thing that can be sequenced, RNA and proteins are sequenced too. In THE CORE we saw that in every cell DNA -> RNA -> protein. Being able to sequence each of these 3 things means that we can learn about what is going on in the two steps: Transcription and Translation. This makes sequencing a standard and very important tool in every biologist's toolkit. 

RNA sequencing actually started before DNA sequencing! The structure of RNA is very similar to DNA, except the backbone is made of slightly different chemicals and all T nucleotides are replaced with U nucleotides. 

messenger RNA or mRNA = an RNA transcript

Remember that every cell in your body has the same DNA but different cell types have different mRNAs and proteins. This means that RNA sequencing is often used to study different cell types. 

Gene = enough DNA to make one transcript and one protein 

Amino acid = a certain type of carbon-containing molecule

Going back to our nerve and gut cells from THE CORE: although the DNA will be the same in the two cells in your body, because different genes are transcribed, the two cells will look different. 

In this picture we are only looking at one mRNA and can see that the nucleotide orders are different. In real life one cell normally has something like 1 000 000 mRNAs at any specific time. The mRNAs are constantly changing as they are being made by transcription and then get broken down. This means not only can we sequence mRNA to tell us about different cell types, but about how a cell is responding to its environment. 

Lastly, proteins can also be sequenced. Remember that proteins are not made out of nucleotides like DNA and RNA, but they have their own building blocks called amino acids. Instead of 4 nucleotides, protein sequencing reads the order of the 20 different amino acids. When you unfold the protein, you can think of it more as a necklace with different coloured beads rather than a ladder with different rungs. The different beads are different amino acids. 

Code for... = same as saying 'has the instructions to make...'

Going back to our nerve and lung cell: from sequencing RNA and proteins we can prove the Central Dogma of Biology. For example in this picture we can see that the mRNA in a nerve cell is AUACGAUU, and this has the instruction to make a myelin protein which is important for the branch-like bits of nerve cells. Lung cells don't have that mRNA, instead they have AUGCGAUU, which makes CFTR channel proteins. A lot of the time scientists only need to sequence the RNA of a cell to know what type of cell it is, from the sequences of the mRNAs we can predict the proteins that cell will have. 

 

(Note that these mRNA sequences are invented for this example, in real life you need much more than 8 nucleotides to code for most proteins, especially big complicated ones!)

 

© 2019 by Biology in Context. Images are from the Public Domain or created with Biorender.com. Website created with Wix.com

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