De novo evolution of genetic function from random sequences

The study of de novo gene birth has opened the doors for evolutionary biologists to approach old questions about the origin of innovation from new perspectives. There are still many questions about what makes a functional gene, how likely it is for a non-coding sequence to become one, how common is this phenomenon in nature, and how do novel genes become essential for an organism. In this thesis, I present three projects that aim to explore some of these questions.

In chapter 1, I revisit a study published in 2017 that used a library of random sequences in E. coli, in order to quantify the likelihood that a random sequence expressed in a cell provides a fitness advantage. I successfully replicated these results, and I improved the analysis pipeline to examine sequences in greater depth. I confirmed that expression of random DNA sequences is well tolerated by E. coli, and found that sequence length is a determinant factor of its effect on fitness. In chapter 2, I transferred the random sequence experiment to a eukaryotic model to determine what proportion of random sequences are well tolerated by eukaryotic cells despite the different complexity. The results indicate that eukaryotic cells are at least as tolerant to the expression of random sequences as bacteria. However, no specific feature of the sequences correlated with their tolerability. Finally, in chapter 3, I expressed three putative de novo genes identified in mouse in a human cell line. The selected genes are taxonomically restricted to species of mice, with transcription and proteomic evidence. Interestingly, expression of the novel genes had little effect on the transcriptome of the cells.

The results presented in this thesis add to the mounting evidence that cells are much more tolerant to the expression of new sequences than previously thought. This insight generates new questions about the birth of genes that should be explored in the future.


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