GeneBites

A new software called Codetta is helping scientists find organisms that read their DNA differently

A great trick of biology is that you can take the DNA for a gene out of one organism and put it in another organism, even a very different one, and it will make the same protein. It’s this amazing trick that has delivered such monumental advances as synthetic insulin, a human protein that bacteria make when given the human insulin gene. However, we’re increasingly finding examples of genomes that can’t translate with such ease.

Our cells read the contents of our DNA in triplets known as codons. There are 64 possible codons that, with some redundancy, instruct the cell on how to build a particular protein. The meaning of each codon is shared so widely throughout the tree of life that it’s often referred to as the “universal genetic code”. But like most biological rules, it’s not really universal. Even within our cells, our mitochondria have maintained their own separate genomes and read things a little differently. These differences in code are not radical. It’s like hearing a different dialect of a language you’re fluent in. The structure of the sentence is the same, so is much of the vocabulary, but every now and then a word or phrase pops up that you don’t know. Sometimes you can put the meaning together with context clues, but other times it derails your understanding of the conversation entirely.

Yekaterina Shulgina and Sean Eddy at Harvard University developed a computer program for identifying organisms that speak their own genetic dialects. Their program, which they named Codetta, looks at proteins that are highly similar between species. If a protein does its job well and is necessary for the life of the cell, it’s unlikely to have changed much, even in very different creatures. Thus, seeing a change in these identical proteins is a tipoff that something interesting might be going on. With Codetta, the researchers looked at these changes across many proteins to find if a codon with one meaning is routinely swapped for another codon with a different meaning. If one particular swap is frequent in a species, that’s a strong sign that the proteins haven’t changed, but the code has.

The researchers both confirmed the existence of known instances of unique genetic codes and discovered new ones. Uncovering more information about species with unusual genetic codes may help us understand how the meaning of a codon can change without massive consequences for the organism. We typically think of evolution as a series of small changes in individual genes, gradually altering a species over time. It’s like changing a word or two with each new copy of a book. The hundredth copy would resemble the original draft, but the meaning of the story would begin to change. However, evolving a new genetic code is riskier than that. It’s like taking a word and changing all instances of its meaning at once, drastically altering the story after just a few copies.

A frequently altered piece of genetic code is a message for “stop”, undoubtedly an important message. If the genome was a driver’s manual and every instance of “stop” suddenly developed a new meaning, there would be a spike in car accidents. Missing “stop” at the ends of genes could also prove disastrous for making proteins, which are essential for cells to function. But there are multiple codons that spell “stop” in the universal genetic code, just as there are multiple words that mean “stop” in the English language. Changing the meaning of a less frequently used word, such as “halt”, shouldn’t have as many effects.

The researchers applied Codetta to the genomes of 250,000 microorganisms and found five groups of bacteria that changed the meaning of codons for a particular protein piece. Four of these species also have genomes that are skewed in which DNA letters they use. The altered codons contained the rarer letters and therefore, these codons appear less often in these organisms’ genomes. Though we’re far from truly understanding how genetic codes evolve, these bacteria show that infrequently used codons may be more amenable to change.

This may just be the start of finding novel ways in which organisms decode their DNA. Of the millions of species on earth, we have genome sequences for only a sliver. In recent years, more projects have emerged vowing to sequence the genomes of wider swaths of biological diversity. This also comes at a time when sequencing a genome is easier and more accessible to research groups studying lesser-known organisms. As more never-before-sequenced genomes come under the scrutiny of scientists, the genetic code may become less and less universal.

Edited by Julia Grzymkowski