Transcription fidelity and transcripts integrity

While DNA stores the blueprint for life, genes must be transcribed into RNA molecules to perform their function. This process of transcription relies on base-pairing to produce accurate copies of DNA templates. We have developed methods to quantify the accuracy of transcription (i.e. how frequently a base in an RNA molecule is different from that in the DNA template it was transcribed from). Our goal is to understand the causes and consequences of transcript errors and to decipher the evolutionary constraints acting on the fidelity of transcription.

We are also interested in understanding how different stressors (such as chemical agents or radiations) affect transcripts integrity.

Related publications:

• Gout, J. F., Li, W., Fritsch, C., Li, A., Haroon, S., Singh, L., ... & Thomas, K. (2017). The landscape of transcription errors in eukaryotic cells. Science Advances, 3(10), e1701484.
• Fritsch, C., Gout, J. F. P., & Vermulst, M. (2018). Genome-wide Surveillance of Transcription Errors in Eukaryotic Organisms. JoVE (Journal of Visualized Experiments), (139), e57731-e57731.
• Gout, J. F., Thomas, W. K., Smith, Z., Okamoto, K., & Lynch, M. (2013). Large-scale detection of in vivo transcription errors. Proceedings of the National Academy of Sciences, 201309843.

Evolution following whole-genome duplication

Whole-Genome Duplications (WGDs) represent one of the most extreme cases of mutation. It has long been hypothesized that duplications (and especially WGDs) provide the main substrate for the evolution of new functions, and therefore are a major source of innovation (Ohno 1970). Moreover, WGDs may promote the emergence of new species through differential retention of duplicated genes in isolated sub-populations after the duplication (Sémon and Wolfe 2007 for review). Indeed, WGDs are typically followed by a period of massive gene loss allowing a reversion to the original level of ploidy, a situation that makes the reciprocal loss of some genes highly probable. Because WGDs have occurred in many different eukarotic lineages (yeast, vertebrates, teleost fish, almost all land plants, ciliates; see Jaillon et al. (2009) for review), elucidating their evolutionary impact is crucial to understanding the genomes of present day organisms.

My main interest is in understanding the mechanisms responsible for gene retention after a WGD. I have studied the impact of gene expression on genes post-WGD evolutionary fate in Paramecium tetraurelia. I found that the level of expression is positively correlated with the probability of gene retention after a WGD and proposed a model based on the cost of expression to explain these observations. The conclusions of these model also shed new light on the impact of expression level on coding sequences evolutionary rates. In the future, analysis of genomes from other Paramecium species that share the same WGDs events may help in refining our understanding of how gene expression impacts post-WGD evolution.

Related publications:

• Gout, J. F., & Lynch, M. (2015). Maintenance and loss of duplicated genes by dosage subfunctionalization. Molecular biology and evolution, 32(8), 2141-2148.
• McGrath, C. L., Gout, J. F., Johri, P., Doak, T. G., & Lynch, M. (2014). Differential retention and divergent resolution of duplicate genes following whole-genome duplication. Genome research, gr-173740.
• McGrath, C. L., Gout, J. F., Doak, T. G., Yanagi, A., & Lynch, M. (2014). Insights into three whole-genome duplications gleaned from the Paramecium caudatum genome sequence. Genetics, genetics-114.
• Gout, J. F., Kahn, D., Duret, L., & Paramecium Post-Genomics Consortium. (2010). The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution. PLoS Genetics, 6(5), e1000944.
• Gout, J. F., Duret, L., & Kahn, D. (2009). Differential retention of metabolic genes following whole-genome duplication. Molecular biology and evolution, 26(5), 1067-1072.