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SUMMARY:Alternative splicing: widespread fine-tuning regulatory process or
  costly errors? - Dr Laurent Duret
DTSTART:20170313T160000Z
DTEND:20170313T170000Z
UID:TALK71446@talks.cam.ac.uk
CONTACT:46487
DESCRIPTION:Most eukaryotic genes are subject to alternative splicing (AS)
 \, which may contribute to the production of functional protein variants o
 r to the regulation of gene expression\, notably via nonsense-mediated mRN
 A decay (NMD). However\, a fraction of splice variants might correspond to
  spurious transcripts\, and the question of the relative proportion of spl
 icing errors vs. functional splice variants remains highly debated. We pro
 pose here a test to quantify the fraction of AS events corresponding to er
 rors. This test is based on the fact that the fitness cost of splicing err
 ors increases with the number of introns in a gene and with expression lev
 el. We first analyzed the transcriptome of the intron-rich unicellular euk
 aryote Paramecium tetraurelia. We show that both in normal and in NMD-defi
 cient cells\, AS rates (intron retention\, alternative splice site usage o
 r cryptic intron splicing) strongly decrease with increasing expression le
 vel and with increasing number of introns. This relationship is observed b
 oth for AS events that are detectable by NMD or not\, which invalidates th
 e hypothesis of a possible link with the regulation of gene expression. Ou
 r results indicate that in genes with a median expression level\, 92%-98% 
 of observed splice variants correspond to errors. Interestingly\, we obser
 ved the same patterns in human transcriptomes. These results are consisten
 t with the mutation-selection-drift theory\, which predicts that genes und
 er weaker selective pressure should accumulate more maladaptive substituti
 ons\, and therefore should be more prone to errors of gene expression.\n\n
 --------------------------------------------------------\n\nLaurent Duret\
 nCNRS Research Director\, Université de Lyon Head of the group: ‘Bioinf
 ormatics\, Phylogeny and Evolutionary Genomics’\n\nHis line of research 
 deals with understanding the processes that drive genome evolution. He inv
 estigates the relative contribution of selection\, mutation\, drift and bi
 ased gene conversion (BGC) to the evolution of genomic features\, with the
  ultimate aim of better characterising functional genetic elements.\n\nhtt
 ps://lbbe.univ-lyon1.fr/-Duret-Laurent-.html?lang=en\n
LOCATION:CRUK CI Room 009/009A
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