Life is complicated. When I was in college and friends asked me why I loved the TV show “LOST”. Anyone who watched a random episode in the middle of the season usually came away from it confused and complained about its complexity. But to me, that was the beauty in that TV show. That it was complicated. It always made you wonder and think about it the next day and chat about it around the water cooler. Well, that’s if you had a water cooler. As a college student, I had the downstairs lounge late night chats. And as a teacher, I never had time to chat around the water cooler.
When people ask me why I love Biology, I tell them it is for that same reason. Life is complicated and that is what makes it beautiful and so interesting. And as we study it more and more, we find that statement to be more and more true. A great example of this is a study headed by John Zaborske called “A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus”. This recent study has demonstrated that silent mutations might be important after all and not so silent!
In our genetic code, there are sections of our DNA (often referred to as “genes”) that are transcribed or “copied” into messenger RNA (sort of like photocopies) in a process called transcription. Each specific messenger RNA copy is used by the ribosomes in the cells as instructions on how to build a specific protein in a process called translation. The messenger RNA copy has sets of 3 nucleotides (like AAC or UUG) called codons and each codon is an instruction for which amino acid to place in a protein’s amino acid sequence. Transfer RNA molecules with three nucleotide codes called anti-codons travel to the ribosome, line up next to the matching codons, and carry the right amino acids to the ribosome to be placed in the right spots in the protein sequence. There are 20 different common amino acids found in the cell and there are technically 64 different codon possibilities. So more than one codon can code for a particular amino acid. For example, UCU, UCC, UCA, and UCG all code for the amino acid Serine. Proteins are like little machines. They all have their own little unique jobs and their ability to do their jobs depends on an accurate amino acid sequence and whether they fold into their unique shapes accurately.
Within the gene sections, there can be occasional mutations. Mutations are often simple substitutions, such as an Adenine for a Guanine. When the mutated gene’s information is copied into a messenger RNA and used to produce a protein, sometimes that protein has missing pieces or production is cut short, producing a useless protein or even sometimes a harmful protein. Occasionally, there is a mutation that scientists call “silent” because it doesn’t change the amino acid sequence. For example, if a messenger RNA’s sequence originally had UCC at a particular spot in its sequence and a mutation in the DNA caused that mRNA to have a sequence of UCG, both the original protein and new “mutated” protein would have Serine at that spot in the amino acid sequence. For many many years, scientists believed that this mutation was harmless and had no effect on the cell.
As it turns out, life is a lot more complicated than that. In this study, the scientists actually found that which codon a messenger RNA has actually matters! Even if they code for the same amino acid (like UCC and UCG coding for Serine), codons can actually change a few different things. Recent studies have shown that different codons can change how stable a particular mRNA is. Sometimes a highly stable messenger RNA can fold on itself and slow down protein production. Less stable messenger RNA’s often produce higher amounts of protein. Some codons, even if they translate into the same amino acid, are translated at different speeds. When codons are translated slowly, ribosomes often pause and this can be important for proper protein folding. Proteins begin to fold as they are built by the ribosome and how they fold is a huge field of study. Ribosome translation speeds and pauses may have a large effect on how successfully the protein folds into its final functional shape.
And to all these codon differences, add in the fact that there are other rare nucleotides like queuosine (Q) that can replace Guanosine (G). The amount of Q available in a cell depends on the animal’s diet and who knows what other factors! Q-containing tRNA molecules translate codons like AAC much faster than they translate AAU codons, adding a whole ‘nother level of complexity!
This is just so cool to think about. That “silent mutations” actually could cause proteins to misfold or could cause proteins to be produced at noticeably different rates or at different amounts! This was definitely not what I learned about in high school biology. When I taught AP Biology, when we had a free moment, I liked to point out new studies or new developments in science that turn what we are actually teaching on its head. I find that my students always were intrigued and wanted to know more.
Life is complicated. And that’s what makes it so amazingly interesting to me. I plan on writing a series of posts about the complexity of life in the coming months and I will link to them here when I do. Make sure you add my blog to your RSS feed if you want to read more!
What amazes you about the complexity of life? Share it in the comments section below!