prediction of selenoprotein genes in eukaryotic genomes roderic guigó i serra, bioinformatica, UPF curs 2005/2006 11/29/2018 Bioinformatica UPF març 2006

what are selenoproteins? Selenoproteins are proteins that incorporate selenocysteine, the 21st aminoacid Mostly redox enzimes Distributed in the three domains of life About 25 known selenoproteins in mammals, but the number varies for different taxa 11/29/2018 Bioinformatica UPF març 2006

selenocysteine 11/29/2018 Bioinformatica UPF març 2006

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the selenocysteine codon? 11/29/2018 Bioinformatica UPF març 2006

the selenocysteine codon:UGA 11/29/2018 Bioinformatica UPF març 2006

recoding of UGA 11/29/2018 Bioinformatica UPF març 2006

the dual function of UGA compounds the identification of selenoproteins 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: SECIS search SECIS came in a variety of sequences 11/29/2018 Bioinformatica UPF març 2006

SECIS search: PatScan 11/29/2018 Bioinformatica UPF març 2006

SECIS search in the Drosophila genome 35,876 potential SECIS elements 1,220 termodynamically stable 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: codon bias 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: codon bias Protein coding codon bias No codon bias selenoprotein TGA STOP Non selenoprotein TGA STOP 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: codon bias Coding Potential Coding region TGA - STOP STOP - STOP 10 SPs 10.21 9.90 -0.16 1169 non-SPs 8.37 -0.83 -2.52 Coding Potential: from the bias in the use of amino acids and, moreover, synonimous codons. 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: SECIS + exon prediction Predict SECIS with PatScan Gene prediction with geneid (allowing TGA-interrupted exons) Geneid uses dynamic programming to chain input exons into gene structures maximizing a log-likelihood function. SECIS predictions and TGA-interrupted exons are now among the input exons. Chaining rules state that SECIS elements can only be chained if they terminate genes containing TGA exons, and that genes containing TGA exon can only be terminated by SECIS predictions. 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: 5’ 3’ SECIS elements and genes are predicted independently along the DNA sequence, but joined in the final gene prediction in such a way that SECIS elements are only allowed after a gene containing a TGA in-frame (within a defined range). 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: 5’ 3’ SECIS elements and genes are predicted independently along the DNA sequence, but joined in the final gene prediction in such a way that SECIS elements are only allowed after a gene containing a TGA in-frame (within a defined range). 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search: 5’ 3’ SECIS elements and genes are predicted independently along the DNA sequence, but joined in the final gene prediction in such a way that SECIS elements are only allowed after a gene containing a TGA in-frame (within a defined range). 11/29/2018 Bioinformatica UPF març 2006

Independent but coordinated selenoprotein search: Putative selenoprotein 5’ 3’ SECIS elements and genes are predicted independently along the DNA sequence, but joined in the final gene prediction in such a way that SECIS elements are only allowed after a gene containing a TGA in-frame (within a defined range). Independent but coordinated TGA in-frame gene and SECIS prediction 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search in Drosophila (Castellano et al selenoprotein search in Drosophila (Castellano et al. EMBO Reports 2:697-702, 2001) SECIS predicted 35876 SECIS thermo assessment 1220 Genes predicted 12194 Predicted Selenoproteins (4) Real Selenoproteins 3 11/29/2018 Bioinformatica UPF març 2006

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dSelG 11/29/2018 Bioinformatica UPF març 2006

dSelH 11/29/2018 Bioinformatica UPF març 2006

dSelG and dSelH are ubiquitous selenoproteins 11/29/2018 Bioinformatica UPF març 2006

dSelH has selenoprotein homologues in vertebrates 11/29/2018 Bioinformatica UPF març 2006

selenoprotein search in mammalian genomes Larger genome. Much more room for false positive SECIS predictions Poorer gene predicitons. 11/29/2018 Bioinformatica UPF març 2006

conserved SECIS between human and mouse 11/29/2018 Bioinformatica UPF març 2006

characterization of mammalian selenoproteins (Kryukov et al., Science 300:1439-1443, 2003) 11/29/2018 Bioinformatica UPF març 2006

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selenoprotein search in other vertebrate genomes 11/29/2018 Bioinformatica UPF març 2006

human vs. fugu 11/29/2018 Bioinformatica UPF març 2006

SelU: a novel selenoprotein family (Castellano et al SelU: a novel selenoprotein family (Castellano et al., EMBO reports 5:71-77, 2004) 11/29/2018 Bioinformatica UPF març 2006

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SelU: exonic structure, and SECIS elements 11/29/2018 Bioinformatica UPF març 2006

SelU: a novel selenoprotein family 11/29/2018 Bioinformatica UPF març 2006

SelU: scattered phylogenetic distribution 11/29/2018 Bioinformatica UPF març 2006

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Fig. 1. SelJ gene and SECIS structure Castellano, Sergi et al. (2005) Proc. Natl. Acad. Sci. USA 102, 16188-16193 11/29/2018 Bioinformatica UPF març 2006 Copyright ©2005 by the National Academy of Sciences

Fig. 2. 75Se labeling Castellano, Sergi et al. (2005) Proc. Natl. Acad. Sci. USA 102, 16188-16193 11/29/2018 Bioinformatica UPF març 2006 Copyright ©2005 by the National Academy of Sciences

Fig. 3. Subcellular localization of SelJ Castellano, Sergi et al. (2005) Proc. Natl. Acad. Sci. USA 102, 16188-16193 11/29/2018 Bioinformatica UPF març 2006 Copyright ©2005 by the National Academy of Sciences

SelJ and crystallins 11/29/2018 Bioinformatica UPF març 2006

Fig. 4. Expression pattern of the SelJ gene during development in zebrafish embryos Castellano, Sergi et al. (2005) Proc. Natl. Acad. Sci. USA 102, 16188-16193 11/29/2018 Bioinformatica UPF març 2006 Copyright ©2005 by the National Academy of Sciences

the eukaryotic selenoproteome 11/29/2018 Bioinformatica UPF març 2006

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SELENOPROTEINS University of Nebraska IMIM, Barcelona Gregory V. Kryukov Sergey V. Novoselov Vadim N. Gladyshev IBMC, Strasbourg Alain Lescure Alain Krol IMIM, Barcelona Sergi Castellano Charles Chapple Universitat de Barcelona Marta Morey Montserrat Corominas Florenci Serras Harvard Unversity, Boston Nadia Morozova Marla J. Berry 11/29/2018 Bioinformatica UPF març 2006

sergi in hawaii 11/29/2018 Bioinformatica UPF març 2006