Unanticipated Genetic Variation: A Serendipitous Finding that Challenges Genetic Principles

Scientists have encountered an unforeseen genetic deviation in a newly identified species of protist, a discovery that questions long-held assumptions regarding the translation of DNA into proteins and underscores the enigmas yet to be unraveled in the natural world.

During an experiment designed to introduce a novel single-cell sequencing method, researchers inadvertently altered prevailing theories about genetic rules.

In an effort to understand this diverse group of organisms better, the genome of the protist exposed an unprecedented divergence in the DNA sequence that indicates the termination of a gene.

Dr. Jamie McGowan, a postdoctoral researcher at the Earlham Institute, conducted genome sequencing of a microscopic organism, a protist, which was sourced from a freshwater pond at the University of Oxford. Dr. McGowan was part of a larger collaborative effort between scientists at the Earlham Institute and Professor Thomas Richards’ group at the University of Oxford, intended to evaluate the efficacy of a DNA sequencing pipeline suitable for minuscule DNA samples, including DNA from a singular cell.

Unforeseen Genetic Anomalies in Protists

Upon examination of the protist’s genetic code, named Oligohymenophorea sp. PL0344, the organism was revealed to be a novel species with an atypical alteration in the manner in which its DNA is translated into proteins.

Dr. McGowan noted, “The choice to sequence this particular protist was purely fortuitous, and it accentuates the extent of our limited understanding of protist genetics.”

Protists as a group defy generalization. While primarily microscopic and unicellular, like amoebas, algae, and diatoms, some multicellular forms such as kelp and red algae also exist.

Dr. McGowan added, “The term ‘protist’ is broadly defined as any eukaryotic organism not classified as an animal, plant, or fungus. This is a reflection of the incredible variability within this group, ranging from organisms that are predators to those that photosynthesize.”

Genetic Alterations in Ciliates

Oligohymenophorea sp. PL0344 is a type of ciliate, a microscopic organism found almost ubiquitously in aquatic environments. Ciliates have proven to be regions of considerable genetic variation, particularly in the assignment of stop codons—TAA, TAG, and TGA—generally used to signal the end of a gene.

Such variations in the genetic code are extraordinarily uncommon. In the rare instances that such variations are reported, TAA and TAG typically have identical translations, suggesting their evolutionary paths are intertwined.

Dr. McGowan elaborated, “In virtually all other known instances, TAA and TAG change simultaneously. When not serving as stop codons, both codons usually signify the same amino acid.”

Anomalies in Gene Translation

In essence, DNA serves as a set of instructions, akin to a blueprint. For a gene to be functional, these instructions must be transcribed into an RNA copy, which is then translated into a chain of amino acids. This chain eventually folds into a three-dimensional molecule, eliciting a physiological effect. Gene translation typically commences at the start codon (ATG) and concludes at a stop codon, usually TAA, TAG, or TGA.

Remarkably, in Oligohymenophorea sp. PL0344, only TGA serves as a stop codon. Dr. McGowan found an unexpected abundance of TGA codons in this organism’s DNA, believed to offset the absence of the other two stop codons. Intriguingly, TAA and TAG were found to specify different amino acids: lysine and glutamic acid, respectively.

“This finding is highly unusual,” said Dr. McGowan. “This is the first instance we know of where these stop codons are correlated with two disparate amino acids. It questions some fundamental principles we thought were established about gene translation.”

This research was funded by the Wellcome Trust within the scope of the Darwin Tree of Life Project and was also supported by the Earlham Institute’s core funding from the Biotechnology and Biological Sciences Research Council (BBSRC), a component of UKRI.

Reference: “Identification of a non-canonical ciliate nuclear genetic code where UAA and UAG code for different amino acids” by Jamie McGowan, et al., published on October 5, 2023, in PLOS Genetics. DOI: 10.1371/journal.pgen.1010913.

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More about genetic variation in protists

• PLOS Genetics: Identification of a non-canonical ciliate nuclear genetic code
• Earlham Institute
• Wellcome Trust
• Darwin Tree of Life Project
• Biotechnology and Biological Sciences Research Council (BBSRC)
• University of Oxford
• Genetic Code
• DNA-to-Protein Translation
• Protists: Definition and Types