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

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Presentation on theme: "Prediction of selenoprotein genes in eukaryotic genomes roderic guigó i serra, bioinformatica, UPF curs 2005/2006 11/29/2018 Bioinformatica UPF març."— Presentation transcript:

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

2 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

3 selenocysteine 11/29/2018 Bioinformatica UPF març 2006

4 11/29/2018 Bioinformatica UPF març 2006

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

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

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

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

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

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

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

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

13 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

14 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

15 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

16 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

17 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

18 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

19 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

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

21 11/29/2018 Bioinformatica UPF març 2006

22 dSelG 11/29/2018 Bioinformatica UPF març 2006

23 dSelH 11/29/2018 Bioinformatica UPF març 2006

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

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

26 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

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

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

29 11/29/2018 Bioinformatica UPF març 2006

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

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

32 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

33 11/29/2018 Bioinformatica UPF març 2006

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

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

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

37 11/29/2018 Bioinformatica UPF març 2006

38 11/29/2018 Bioinformatica UPF març 2006

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

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

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

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

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

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

45 11/29/2018 Bioinformatica UPF març 2006

46 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

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

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