Genes: Why is the elephant different from the ant?

The scientists of the institute compared the genomes of nine yeast strains, identified about 2,800 common genes, and examined the causes of the differences between the strains

Orna Man and Dr. Tzachi Pepper. silent mutations

Why is the elephant different from the ant? This basic and ancient question has occupied generations of naturalists, who are trying to identify the source of the huge variety of living creatures on Earth. Over the years, several possible answers to this question have been found. The simplest of them says that the difference between the creatures is due to their gene set: a bacterium with a shooton contains a set of genes that is not found in a bacterium that does not have a shooton. Simple and instinctive as it may be, this explanation is insufficient, as creatures very different from each other contain a surprisingly large amount of identical genetic material.
Humans and chimpanzees, for example, share about 99% of their genetic material. Another explanation says that shared genes can also contribute to variation between organisms, when they are activated
in different intensities, locations and timings. According to this explanation, the genetic control system that oversees the expression of genes, that is, the process of their transformation into active proteins, is largely responsible for the variation between organisms. This control system operates in two stages: the first stage, on which the main research is focused, is the "copying" - the creation of a messenger RNA molecule based on a section of DNA. The second stage is the "translation" stage, in which a protein is created based on the messenger RNA molecule.
Dr. Tzachi Flafel from the Department of Molecular Genetics, and research student Orna Man, who is also guided by Prof. Yoel Sussman from the Department of Structural Biology, chose to focus on this less researched stage, and tested whether it is possible that the translation process may also cause differences between organisms.
Dr. Pepper and Orna Man focused on the "synonymous words" in the genetic book. What are these words? As you know, the DNA sequence consists of sequences that include four letters: A, T, G and C. Each three-letter "word" creates a "codon" that marks a certain amino acid, each "sentence", or gene, is responsible for creating a protein .
Since the number of possible codons (64) is greater than the number of amino acids (20), each amino acid is encoded by several combinations. Scientists used to refer to them as "synonyms" - replacing a codon with a synonymous codon (as a result of a mutation) will not affect the protein that will be produced from the gene.
Until now, it was common to assume that these mutations, known as "silent mutations", are not expressed in the creature that underwent the mutation, and therefore do not cause differences between creatures, nor do they cause genetic diseases. Dr. Pepper and Orna Man's research, recently published in the journal Nature Genetics, shows that differences in the rate and efficiency with which the synonymous codons are translated affect the characteristics of the entire organism.
Why is translation efficiency different for different synonymous codons? The reason for this is that for each codon there is a unique molecule, called transfer RNA, whose role is to lead the amino acid corresponding to the codon to the protein that is being built.
The efficiency of translation depends on the frequency of different transfer RNA molecules: the greater the frequency of transfer RNA molecules corresponding to a certain codon, the faster the translation will be. The researchers compared the genomes of nine yeast strains, and identified about 2,800 genes in common. Then they calculated the translation efficiency of these genes, according to the codons that make them up.
It turns out that there are indeed large differences in the translation efficiency of the genes in the different species, and that there is a connection between the translation efficiency and the characteristics of the yeast species. Thus, for example, yeasts that prefer to derive the energy they need from oxygen (aerobic species) have very efficiently translated the genes needed to perform this activity. In contrast, yeast species that produce energy
Without oxygen (fermenting yeast), they favored efficient translation of other genes. Dr. Pepper: "A certain lifestyle, which requires increased expression of certain genes, will cause a preference for the representation of these genes using codons that are translated with the highest efficiency. This preference is achieved by natural selection pressures."
One of the important consequences of the research concerns the role of "silent mutations" as causes of diseases. Until now, scientists have looked for mutations that change the sequence of amino acids, with the assumption that only such mutations cause a disturbance in the protein's function and therefore cause diseases. Dr. Pepper's research draws attention to the silent mutations, which, as it turned out, have a considerable effect on the character and functioning of living beings.

From issue number 47 of the Weizmann Institute magazine