Daily Archives: October 7, 2018

Whipping the Worm

Last November, I burbled on the IRIS project about curating the Human Whipworm Genome. A lot of genes have flowed across our screens since then, and as the project enters its second year I still have over 50 students from Years 10, 11, 12 and 13 enthusiastically learning about genome curation and putting it in to practice.

But this year I also want to start explore its potential for A-level teaching. See what you think…

Take a look at this screenshot from the Apollo genome editing software.

screenshot Apollo pic

Ooops. I work across 2 screens and I always forget that screenshots grab both of them.

OK, ignore the photo on the left, which shows my youngest son George in the process of diving into his snow burrow last winter. We need to focus on the image on the right. Let me try some judicial cropping…

screenshot Apollo pic

Ah! That’s more like it. So, what to look for?

First, notice how it’s divided into two vertical sections – the thinner one on the right with the heading “tracks” – we’ll come back to that. For now, concentrate on the left hand division. It has a few bars at the top, with zoom in/out icons and left right arrows, below that a yellow area with a long thing in it, and below that a thick white area with lots of horizontal parallel bars of  various colours and lengths.

First thing to notice, check out the numbers at the top of this left hand section.

5,000,000…… 10,000,000……15,000,000…. all the way up to 30,000,000…

These refer to the number of base pairs on the bit of whipworm genome we’re looking at. 30 million base pairs long!!!! This is a serious chunk of DNA! And if you look in the middle top, TTRE,chr2, it tells you we’re looking at the entire length of Chromosome 2 of the Whipworm. It’s there, on the screen, right in front of you, sequenced and accessible and real. Mind blowing.

I think this is an extraordinarily powerful image for conveying exactly what a genome is. But what makes it even more powerful is what you can then do with it.

Let’s change the view – we can do this by turning the various tracks in the right hand column on and off.

apollo screen grab

Now we’re looking at a chunk – a scaffold – of chromosome 1. Although chromosome 1 has been sequenced, the precise order of the sequenced sections has not yet been determined. So this is scaffold 1 of chromosome 1. Notice that it’s quite a bit shorter than chromosome 2, measuring just over 11,000,000 base pairs long.

I’ve zoomed in to create a view between 5,550,000 bp and 5,800,000 bp on the scaffold. I’ve selected tracks that just show the computer predictions of which parts of the genome look like genes. These are the things visible in the white area.

There is a huge amount of information about the nature of DNA in that image! When a student reaches the point where they fully understand it, they’re becoming reasonably fluent in the topic.

I’ve used lots of analogies down the years to try and help students understand the differences between DNA, genes, chromosomes and genomes. This picture illustrates all of this and more. So the 11,000,000 letters? That’s the DNA. A continuous strand, extraordinarily long, comprising an unbroken sequence of the 4 DNA letters. We can zoom in for a closer look…

genome zoomed in

Notice just how zoomed in we are… a span from 5,670,850 to 5,671,000, just 150 letters, and look!, you can see them! In the middle. That’s  DNA, sequenced, and on display, part of the genetic code that provides information for making Whipworms. The coloured bars above and below it, with their mysterious asterixes and highlighted letter Ms can wait for now, though I expect most of you can work out what they refer to…

Again, I just find this utterly amazing. The power of this software! And we’ll be using this zoomed in scale when we’re fine tuning our gene edits, but let’s go back to that other image.

apollo screen grab

Having established what DNA is, students can now readily see that a chromosome is just a very very long chunk of the stuff.

So what are the genes?

Well, again, there they are, the discreet horizontal line/bar combos in the white area (though it’s important to note at this stage that these are just the computer predictions as to which bits of the genome look like genes – sometimes the predictions are right, but all too often they’re wrong, to a greater or lesser degree, which is why the genome needs to be manually curated). But for now, let’s just take them at face value.

And let’s have a closer look at some…

apollo screen grab

Here are ten. Gene 1211 to Gene 1220. Notice that they correspond to the section of DNA directly above them on the genome – their position, or locus, on the chromosome. Notice that they vary in length – gene 1215 looks quite substantial, gene 1220 is diddy. Notice that they’re made up of coloured blobs connected by long, thin lines. Notice that there are overlaps between neighbouring genes. Notice that there are gaps. And notice that they each have an arrow at one end – for some, the arrow points to the right, for the others, the arrow points to the left.

This last observation illustrates another key point about DNA – being double stranded, the information, the code, the gene, could be on either strand. But the strands are anti-parallel, they run in opposite directions, so when curating the genes, you have to know whether they need to be read from left to right, or from right to left…

This year, I plan to get all of this in place with the Year 12s before we start looking at the actual structure of the molecule. How the students will then use the software to learn more about genes and what they do….

…. is a topic for another burble.

Watch this space!