Sequencing human genomes is now routine at the Sanger Institute. Bacteria, yeast, worms, malaria, and other pathogens are also all regularly sequenced in their thousands. Our people are pretty well known for sequencing the human genome, but we’ve also contributed to the first sequencing of many others including the mouse, rat, zebrafish, pig and gorilla too.
The 25 genomes project is an entirely different beast. It’s posing some new, and frankly very odd, challenges. The diversity of the new species means we’ve had a steep learning curve. Here’s a peek at some of the weird and wonderful things we’ve discovered so far:
New Zealand flatworms will explode if you freeze them - not terribly helpful when trying to extract DNA from samples... Image Credit: S. Rae, Wikimedia Commons
1. Don't freeze flatworms
You may well ask why we’d freeze them in the first place. But freezing samples, or in this case, whole worms, is standard practice to store them ready for DNA extraction.
Freezing New Zealand flatworms didn’t go so well though. The resulting sticky goop proved difficult to handle... and to get DNA from.
Is this the Oxford Ragwort you are looking for? The best way to know is take a picture and send it to an Oxford expert... Image credit: Rosser1954, Wikimedia Commons
2. It’s good to get a second opinion when you’re identifying something
The Oxford ragwort was chosen to sequence in our flourishing category. We have ragwort growing here on campus, so we took a plant for sequencing.
But once we started, we soon realised it was not the ragwort we were looking for. The plant we had was hexaploid (it has 6 copies of its genome in every cell). The Oxford ragwort, which we were hoping to sequence, is diploid (it has 2 copies).
We sent a photo of the plant to an expert at Oxford University, who informed us we had the common ragwort.
There 300+ species of blackberry - and telling them apart can literally take years of observation. Image credit: Fir0002, Wikimedia Commons
3. There are over 300 species of blackberry in the UK
They differ in a whole host of characteristics; sweetness, number of drooplets (the little blobs that make up the fruit), colour, size, thorns, flowers, lifecycle and more.
Finding the right one wasn’t easy, but we did sequence the correct one first time this time. Read more about the blackberry saga.
4. Fen raft spiders are more popular than beavers
In a public vote, the fen raft spider won out over the beaver to have its genome sequenced.
Both species were up against other as contenders in the flourishing category of the project.
Over 5,000 votes were cast in total, as part of “I’m A Scientist Get Me Out Of Here”.
Scottish Featherworts are a lonely bunch, they're all male and their female partners are more than 4,428 miles away. Image credit: David Freeman, RSPB
5. All the featherworts in Scotland are male
Their potential partners are over 4,500 miles away in the Himalayas.
Botanists don’t know when the populations split, or how they got there.
They only reproduce clonally in Scotland, and so it is uncertain how long they can last in this way.
Bush crickets have issues #2 - they have cannibal tendencies. Image credit: Richard Bartz
6. Genomes are not always what you expect
We estimated that the genome of the bush cricket would be 2Gb, about 2/3rds the size of the human genome. We were wrong.
The estimate was based on the average cricket genome from the animal size genome database. But in fact it is 2.5 times larger than the human genome, coming in at 8.5Gb.
Read more about how this affected the sequencing.
7. It’s good to share
We knew this already, but this project has been a huge collaborative effort. It wouldn’t have been possible without scientists giving their time and sharing their expertise.
The Natural History Museum are a key partner for the 25 genomes project. They are helping with species identification and collection, as well as providing a link to natural historians and species experts across the UK.
The sequencing itself wouldn’t have been possible without PacBio. They have provided a machine for the project and provided expert technical support to enable the sequencing of the new species.
Our other collaborators include EMBL-EBI, The National Trust, The Wildlife Trust, Royal Society for the Protection of Birds (RSPB), Nottingham Trent University, Edinburgh University, 10x Genomics, Illumina and many more. See the full list here.
8. Don’t put bush crickets in a box together
They eat each other (or parts of each other).
Scallops are 20 times more genetically diverse than humans. Image credit: Asbjorn Hansen
9. Scallops are more diverse than people
We’ve found that scallops have 20 times the diversity of humans.
The king scallop was sequenced in the dangerous category of creatures. Human genomes are just 0.1 per cent different to each other – that is, only 0.1 per cent of your DNA code is different to any other person on the planet.
We have a pretty good idea why human genomes are so similar. It’s likely that events in our evolutionary past, like ice ages or infectious diseases caused a genomic bottleneck, which meant only a small group survived.
In scallops, 1.7 per cent of the DNA differs between any given individuals.
10. We can go faster than we thought
This project started in January 2018. We're barely into October.
We’ve sequenced 25 new genomes in less than 10 months.
The PacBio machines we are using have doubled the amount of data they produce, per run, in the last 12 months. Next year, they will quadruple capacity.