Researchers at the Smurfit Institute of Genetics at Trinity College Dublin and the School of Medicine at the University of Pittsburgh have recently uncovered secrets about De novo genes, which are genes that have evolved from scratch. These genes do not have related genes in the genomes of the species family. They seemingly arise from nowhere, not brought on by evolutionary pressure. The researchers used yeast samples in which they induced De novo gene functions to see the practical effect and rate of emergence of these genes.

De novo gene birth in yeast has now been proven to be a phenomenon that is more common than we first thought. We now know how to create De novo genes that are fitter and more adaptable than established genes.

Most genes have cousin genes in the genome that are made of similar DNA sections and are translated to proteins with similar functions. Orphan genes are those that do not show these features and emerge in an unpredictable manner. This poses tough evolutionary problems as to where they come from. It was thought that they mostly came from divergence, where genes that are similar diverged in their code overtime through evolution. This new research suggests that that is not the case.

The researchers discovered that only 1/3 of orphan genes come from divergence which in turn suggests that they mostly arise from other processes, namely, the De novo process. In De novo, complexes arise a new with no pre-existing structure. The researchers discovered that most orphan genes are De novo genes because they arise from genetic material that had previously not been used to code genes and make proteins. So, these genes show De novo emergence as they are created from material that was not being previously used to make genes.

The evolutionary function for this emergence is thought to be that this exposes a reservoir of variable genetic data to natural selection as this data will be used to make genes and then proteins. This allows for the purging of this potentially toxic genetic data from the species. Once the mechanism for this emergence was determined, the researchers studied the importance of these genes by observing the effect of their functions on the fitness of the species.

The researchers induced overexpression of these genes, where large quantities of these genes are created which in turn creates high numbers of their corresponding proteins, in budding yeast samples. The fitness of these emerging genes was compared against established genes. Fitness was compared by large deletions of non-essential genes and then essential genes. In this way, fitness estimates were obtained for 239 emerging genes and 4,410 established genes. Gene fitness was then examined in natural conditions created by varying oxygen, carbon, and nitrogen levels.

What was discovered was that in normal expression, only 8% of emerging genes showed beneficial fitness effects, markedly less than the 29% of established genes. However, when the emerging genes were overexpressed, they were 4.5 times more likely to increase fitness, and 3.1 times less likely to decrease fitness, which was more than that of established genes. Furthermore, these new genes were never found to be toxic in any of the conditions tested and their cells also showed faster growth leading to completely viable cells. Meanwhile, established genes showed no improvement when overexpressed.

 

Sources:

Vakirilis, N., et al. 2020. De novo emergence of adaptive membrane proteins from thymine-rich genomic sequences. Nature Communications. 11(781).

Link: https://www.nature.com/articles/s41467-020-14500-z

Vakirilis, N., Carvunis, A-R., McLysaght, A. Synteny-based analyses indicate that sequence divergence is not the main source of orphan genes. eLife. 9.

Link: https://elifesciences.org/articles/53500