• Aryan Shah

The Opinion - Efforts to sequence DNA of life in the UK helps to understand and protect Earth

The Natural History Museum in London are embarking on a mission, a new mission to sequence the genomes of 66,000 species in the UK (all eukaryotes) in a space of 10 years. Why, you ask? The words of the Director of Science at the Museum, Dr. Tim Littlewood should clear things up, "the history of how every organism has diverged and adapted to its environment is recorded in its genetic makeup...understanding natural processes and adaptations to diverse environments developed by different organisms will provide a spectacular resource for tackling current and future challenges". The first steps to achieve such a magnificent feat reads much like a story, as this is not something that just HAPPENS, it is a process and will take time to work.

But, wait, what is DNA sequencing Aryan? Well, here's how it works.

1) A Polymerase Chain Reaction (PCR) is used to amplify a sample of DNA into millions of copies, so the researchers can study it

2) In the PCR, primers must be used to select specific sequences of DNA to be amplified. The primers are also essential for Taq Polymerase to attach and catalyse the formation of new DNA strands with the free nucleotides there

3) A DNA strand is combined with DNA Polymerase, a primer (to help with direction) and free nucleotides. They are all coloured with dye and a STOP codon of dideoxy nucleotides added to end the process of adding nucleotides to the strand

4) Temperature is raised to denature the lagging strand, then cooled so the primer can attach, then raised AGAIN so the Polymerase can start adding nucleotides in the 5' to 3' direction

5) STOP codon dideoxy nucleotides are placed on the strand and no more nucleotides are added

6) This is repeated many times, leading to the eventual idea that the dideoxy nucleotides as the end point of nucleotide addition, are stationed at every single position on the leading strand at least once (as the reaction has happened again and again and again)

7) There are many stop codons present in the original DNA strand, causing DNA replication to halt at different lengths.

8) Now, this is interesting! The DNA fragments pass through a gel-like substance in electrophoresis and the smallest fragments make it through the gel the fastest, whereas the longer fragments take more time to do so. This is fundamental, as the DNA is not observable, which is why we use probes instead.

9) The nucleotides are all dyed remember? So, a laser is passed through the gel and is detected on the other side, where it is picked up on a computer and a chromatogram, where there are varying levels of intensity of the different colours present in the DNA strand, where the sequence can then and only then be interpreted!

The Museum have put in place a 10 year plan which should go butter smooth, but, did you know that it took 13 years just to map the genomes of humans? Despite this shortened time scale for a much larger project and the fact that technology is somehow functioning in our favour, there is still a lot of logistics involved. The Museum are working together with Universities like Cambridge, Oxford and Edinburgh to get this done as quickly and efficiently as possible. Traditionally, specimens collected can be placed in freezers or cold storage, (like in frozen zoos which tend to have a much higher genetic diversity than normal zoos) to literally freeze all metabolic processes of that organism and its cells and this can primarily stop it from dying, keeping it fresh for samples. Considering that entering the field and the wild of the UK will be a huge part of the process, the teams involved rely on an app called 'Epicollect', software that is used to take photos of a species, record its habitat, its location and its physical features.

Each species that must be transported to the lab for further analysis must be transported in the correct manner, in a safe, secure and effective way. This is where the freezers come in handy! They have "cold-chain equipment at the site, including small freezers that chill to -80 degrees Celsius, cold enough to calm lively insects and spiders to be photographed". However, there is an issue. It's the genetic material they are after, so the -80 degrees is not going to preserve the material for long, which is why they carry along with them, some "vacuum flasks charged with liquid Nitrogen at -196 degrees Celsius, in which we flash freeze the samples".

Once the samples are brought back to the lab, they are placed on ice, boxes, then given a unique "barcode" which is uploaded onto 'Epicollect' to "link each specimen to the sampling data". Of course, insects are tricky little things to work with and are hard to identify just by looking at them!

Right, this is where you might need to concentrate!

It is so key for the team involved to ensure that the organism they are identifying has the right length of DNA in order for sequencing to work, which is why it involves identifying samples by using a short section of DNA called cytochrome c oxidase I (COI), which has "650 base pairs on the mitochondrial genome". Now, the mitochondria is an important organelle in the cell, if not the most important organelle in the cell. It is involved predominantly with apoptosis, aerobic respiration, ATP synthesis and has its' own circular DNA. The idea here, is that the team will extract the COI from an already identified organism and sequence it, allowing them to do this for several specimens, encouraging easy identification of new species and samples without the need to sequence the whole genome!

The Museum aims to complete this mission in 10 years, and it is starting to actually become a reality as their newly acquired machines, such as the PacBio https://www.pacb.com/ which can sequence thousands of samples in one one go, compared to a mear 96 in the past.

Ian Barnes, the research leader and head of division, Earth Sciences, expresses that "the museum holds a species inventory for the UK, collating information from special-interest groups". The benefit of this massive project, is that all researchers will be able to access these genome records once they are done for their own research, allowing them to recognise genetic evolutionary changes and adaptations that lead to the organisms characteristics and how we could use these sequences as an advantage over changing environments and climates.

An example of how this could be used is the effort to understand where the immunity to squirrel pox in grey squirrels comes from, what sequence or nucleotides are involved in this immunity in comparison to the red squirrels who barely manage to survive the outbreak.

You could use this abundance of genomes and sequences to just observe and identify species in an area, such as analysis on a pond, you could take samples and match the sequences present in the water to the ones you already have in your database for easy identification of known or unknown species.

I think this project is fundamental for British biology and many other disciplines of science that are involved, like medicine and palaeontology too. The Museum are ambitious to sequence EVERY species in the UK, which is an immense task and sounds bonkers to me, but it is manageable if you have enough time, energy and the right method to do it. All species in the UK being sequenced allows researchers to easily identify any new species or alien species in our midst that shouldn't be there and can encourage biologists to understand what makes that organism special, by really looking into its' very foundations.




"Mapping the Tree of Life", Evolve magazine, Natural History Museum - date accessed - Thursday 9th of July 2020

Peer reviewed by Lawrence Cutler, thank you!

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