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Jean-François Gout
jgout(at)indiana.edu
(812) 856-0115

PhD from University Claude Bernard, Lyon 1, France. (2009) PhD dissertation (in French) available here : http://lbbe-dmz.univ-lyon1.fr/biblio/pdf/GoutJF2009b.pdf

My broad interests involve the evolution of eukaryotic genomes and how the relative impacts of natural selection and genetic drift can explain the patterns that we observe in extant species. Most of my past work was focused on two aspects of genomes evolution: the selective constraints imposed by the presence of spliceosomal introns and the consequences of Whole-Genome Duplications. For these two studies, I used data from the ciliate Paramecium tetraurelia, whose genome was published in 2006 (Aury et al., 2006, Nature 9;444). Because of its exceptional characteristics, Paramecium tetraurelia is a perfect model organism for these evolutionary genomics studies. For an overview of the Paramecium genome, see Aury et al. (2006) Nature 9;444 and Beisson et al. (2010) Cold Spring Harb Protoc.


  • Paramecium as a model organism

Paramecium are unicellular organisms belonging to the ciliates, a phylogenetic clade showing an amazing level of diversity (see picture below).


All ciliates are unicellular eukaryotes characterized by the presence of cilia that they can use for swimming, feeding or sensation. They are also characterized by the presence of two different nuclei within a single cell. The micronucleus (MIC) is transcriptionnaly silent but undergoes meiosis during sexual reproduction and therefore can be seen as the germline. Genes are transcribed from the macronucleus, which is generated from the MIC after each new sexual generation. The sequencing of Paramecium tetraurelia revealed a complex history of 3 (and probably 4) successive rounds of Whole-Genome Duplications in a highly compacted genome characterized by extremely short intergenic regions and tiny introns (Aury et al., 2006). You will find below the main findings of the studies I was involved in on the Paramecium genome.


  • Selective constraints on spliceosomal introns

Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. However, the removal of introns (a process called splicing) is complex and not 100% efficient. The retention of an intron within mature mRNAs is hazardous because translation of the intronic DNA may lead to the production of a non-fonctional or even toxic protein. However, mRNA surveillance mechanisms such as the Nonsense-mediated mRNA decay (NMD) can prevent the translation of these aberrant transcripts if they contain a Premature Termination Codon (PTC). We observed in the Paramecium genome a strong depletion in introns whose retention preserves the open reading frame (i.e. introns whose length is a multiple of 3 and do not contain any in-frame stop codon). Because missiplicing of these introns cannot be detected by NMD, we propose that selective constraint oppose to their presence in order to avoid the translation of erroneous proteins that can result from missplicing. Interestingly, although the initial observations were made in Paramecium, the conclusions of this work apply to all intron-rich eukaryote we searched for.
For more details, see: Jaillon et al., Translational control of intron splicing in eukaryotes (2008), Nature 451:359


  • Consequences of Whole-Genome Duplications

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.

For more details, see :
Gout JF, 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 Genet. 2010;6(6)

Gout JF, Duret L, Kahn D. (2009) Differential retention of metabolic genes following whole-genome duplication. Mol Biol Evol. 26(5):1067-72


  • Other projects

My other projects and interests include (but not limited to !) : evolution of pseudogenes among eukaryotes, consequences of errors during gene expression (aberrant expression level, transcription errors, missplicing, ...), genomic rearrangements in ciliates and mating type determination in Paramecium.


Publications

Arnaiz O, Gout JF, Betermier M, Bouhouche K, Cohen J, Duret L, Kapusta A, Meyer E, Sperling L. (2010) Gene expression in a paleopolyploid: a transcriptome resource for the ciliate Paramecium tetraurelia. BMC Genomics. 11(1):547

Gout JF, 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 Genet. 6(5):e1000944

Gout JF, Duret L, Kahn D. (2009) Differential retention of metabolic genes following whole-genome duplication. Mol Biol Evol. 26(5):1067-72

Lepère G, Nowacki M, Serrano V, Gout JF, Guglielmi G, Duharcourt S, Meyer E. (2009) Silencing-associated and meiosis-specific small RNA pathways in Paramecium tetraurelia. Nucleic Acids Res. 37(3):903-15

Duret L, Cohen J, Jubin C, Dessen P, Gout JF, Mousset S, Aury JM, Jaillon O, Noël B, Arnaiz O, Bétermier M, Wincker P, Meyer E, Sperling L. (2008) Analysis of sequence variability in the macronuclear DNA of Paramecium tetraurelia: a somatic view of the germline. Genome Res. 18(4):585-96

Jaillon O, Bouhouche K, Gout JF, Aury JM, Noel B, Saudemont B, Nowacki M, Serrano V, Porcel BM, Ségurens B, Le Mouël A, Lepère G, Schächter V, Bétermier M, Cohen J, Wincker P, Sperling L, Duret L, Meyer E. (2008) Translational control of intron splicing in eukaryotes. Nature. 451(7176):359-62