The accidental discovery that shakes genetics

Scientists testing a new method for sequencing single cells have unexpectedly changed our understanding of the rules of genetics.

The protist genome revealed a seemingly unique variation in… DNA A symbol indicates the end of a gene, indicating that more research is needed to better understand this diverse group of organisms.

Dr Jamie McGowan, a postdoctoral scientist at the Earlham Institute, analyzed the genome sequence of a microorganism – a protist – isolated from a freshwater pond in Oxford University Parks.

The goal of this work was to test a DNA sequencing pipeline to work with very small amounts of DNA, such as DNA from a single cell. Dr McGowan has been working with a team of scientists at the Earlham Institute and with Professor Thomas Richards’ group at the Earlham Institute. Oxford university.

Unexpected genetic findings in protists

However, when researchers looked at the genetic code, the protists Hymenophoria sp. PL0344 turned out to be novel Classify With an unexpected change in how its DNA is translated into proteins.

“It’s fortunate that we chose these protists to test our sequence line, it shows just what’s out there, and highlights how little we know about protist genetics,” Dr McGowan said.

It is difficult to make any statements about protists as a group. Most are single-celled microscopic organisms such as amoeba, algae and diatoms, but there are larger multicellular protists – such as kelp, slime molds and red algae.

“The definition of protist is loose – it is basically any eukaryotic organism that is not an animal, plant or fungus,” Dr McGowan said. “This is obviously very general, because protists are a very variable group.

“Some are closely related to animals, others are closely related to plants. There are hunters and prey, parasites and hosts, swimmers, and sitters, and there are those who have a varied diet while others photosynthesize. Basically, we can make very few generalizations.”

Ciliary companies and genetic code changes

Hymenophoria sp. PL0344 is cilia. These swimming protists can be seen with a microscope, and can be found almost anywhere there is water.

Cilia are hotspots for genetic code changes, including reassignment of one or more stop codons—codons TAA, TAG, and TGA. In almost all organisms, these three stop codons are used to indicate the end of a gene.

Variations in the genetic code are extremely rare. Among the few genetic code variants reported to date, the TAA and TAG codons always have the same translation, suggesting that their evolution is coupled.

“In almost every other condition we know of, the TAA and TAG change in tandem,” Dr. McGowan explained. “When they are not stop codons, they each specify the same amino sour“.

DNA translation abnormalities

DNA is like a building blueprint. It does not do anything in itself, but rather provides instructions for the work to be done. For a gene to have an effect, the blueprint must be “read” and then incorporated into a molecule that has a physical effect.

In order for DNA to be read, it is first copied into a file RNA Copy. This copy is moved to another area of ​​the cell where it is translated Amino acidsWhich are combined to form a three-dimensional molecule. The translation process begins at the DNA start codon (ATG) and ends at the stop codon (usually TAA, TAG, or TGA).

in Hymenophoria sp. PL0344, TGA acts only as a stop codon – although Dr McGowan found that there are more TGA codons than expected in cilia DNA, thought to compensate for the loss of the other two. Instead, TAA specifies lysine and TAG specifies glutamic acid.

“This is very unusual,” Dr. McGowan said. “We’re not aware of any other case where these stop codons are linked to two different amino acids. It breaks some of the rules we thought we knew about gene translation — these two codons were thought to be paired.”

“Scientists are trying to engineer new genetic codes – but they also exist in nature. There are wonderful things we can find, if we look for them.

“Or, in this case, when we’re not looking for them.”

Reference: “Identification of the non-canonical ciliary nuclear genetic code where UAA and UAG code for different amino acids” by Jamie McGowan, Estelle S. Killias, Elizabeth Allacid, James Lipscomb, Benjamin H. Jenkins, Karim Gharbi, Jamie J Kethakuttil, Ian C Macaulay, Sianna MacTaggart, Sally D. Waring, Thomas A. Richards, Neil Hall and David Swarbrick, October 5, 2023, PLOS Genetics.
doi: 10.1371/journal.pgen.1010913

This research was funded by the Wellcome Trust as part of the Darwin Tree of Life Project, and supported by core funding to the Earlham Institute from the Biotechnology and Biological Sciences Research Council (BBSRC), part of UKRI.