Annotation and Nomenclature: A Zebrafish Example. Ingo Braasch, Julian Catchen and John Postlethwait

Transcription

1 Annotation and Nomenclature: A Zebrafish Example Ingo Braasch, Julian Catchen and John Postlethwait

2 Annotation and Nomenclature: An Example: Zebrafish The goal Solutions

3 Annotation and Nomenclature: An Example: Zebrafish The goal "Nothing in Biology Makes Sense Except in the Light of Evolution" Theodosius Dobzhansky Amer Biol Teach (1973) 35: Nomenclature should match evolutionary origins Solutions

4 The goal "Nothing in Biology Makes Sense Except in the Light of Evolution" Theodosius Dobzhansky Amer Biol Teach (1973) 35: Nomenclature should match evolutionary origins Gene names should connect fish genes to the human genome Genome duplication Gene losses

5 Annotation and Nomenclature: An Example: Zebrafish The goal "Nothing in Biology Makes Sense Except in the Light of Evolution" Theodosius Dobzhansky Amer Biol Teach (1973) 35: Genome duplication Gene losses Solutions Trees + conserved syntenies

6 Genome duplication Gene losses A. No gene loss g R1 g1 g2 Ohnologs: paralogs from genome duplication Susumu Ohno

7 Genome duplication Gene losses speciation S1 R2 g1a g1b g2a g2b A. No gene loss g R1 g1 S2 G1 G2 g2 Ohnologs: paralogs from genome duplication Susumu Ohno

8 Genome duplication Gene losses speciation S1 R2 g1a g1b g2a g2b A. No gene loss g R1 g1 S2 G1 G2 g2 g1a R2 g1b speciation S1 B. With gene loss R1 g1 S2 g G2 g2 Ohnologs gone missing

9 Genome duplication Gene losses C. With gene loss R1 speciation R2 S1R2 g1a g1b g speciation S1 g1b B. With gene loss g R1 g1 S2 G2 G2 g2

10 Genome duplication Gene losses speciation S1 R2 g1a g1b B. With gene loss R1 g1 S2 g G2 g2 C. With gene loss R1 speciation R2 g1a S1 g g1b G2 erroneously appears as an S2 G2 ortholog of its duplicated paralog g1. Thus, the entire region must be used to determine origins and hence nomenclature. => conserved syntenies

11 Annotation and Nomenclature: An Example: Zebrafish The goal "Nothing in Biology Makes Sense Except in the Light of Evolution" Theodosius Dobzhansky Amer Biol Teach (1973) 35: Genome duplication Gene losses: Ohnologs gone missing Solutions Trees + conserved syntenies S1 S2 g1a g1b G2

12 Annotation and Nomenclature: An Example: Zebrafish The goal "Nothing in Biology Makes Sense Except in the Light of Evolution" Theodosius Dobzhansky Amer Biol Teach (1973) 35: Genome duplication Gene losses: Ohnologs gone missing Solutions Trees + conserved syntenies S1 S2 g1a g1b G2

13 Solutions Trees + conserved syntenies Teleosts can adjust to background color black Background white Zhang found a novel agouti-related gene agrp2 necessary for background adaptation Background black black Zhang et al. (2010) PNAS 107: they imply that this is a novel function that arose in teleosts

14 they imply that this is a novel function that arose in teleosts Hypothesis 1 fish mouse bkd adapt no adapt gain of TGD function no adapt Hypothesis 2 fish mouse bkd adapt no adapt TGD loss of function adapt

15 Hypothesis 1 fish mouse bkd adapt no adapt gain of TGD function no adapt Hypothesis 2 fish mouse bkd adapt no adapt TGD loss of function adapt Tetrapods have 2 agouti related genes Xenopus scaffold38 99 Human chr20 Mouse chr2 71 Chicken chr20 Xenopus scaffold Chicken chr11 Human chr16 Mouse chr8 Asip Agrp

16 Hypothesis 1 fish mouse bkd adapt no adapt gain of TGD function no adapt Hypothesis 2 fish mouse bkd adapt no adapt TGD loss of function adapt Tetrapods have 2 agouti related genes Teleosts have 4 Tree suggests nomenclature problems Fugu scaffold446 Tetraodon chrun Stickleback chrxvii Zebrafish chr6 Xenopus scaffold38 Human chr20 Mouse chr2 71 Chicken chr20 Fugu scaffold427 Tetraodon chrun Stickleback chrxxi 61 Medaka chr20 96 Fugu scaffold166 Tetraodon chr15 98 Medaka chr17 Stickleback chriii Zebrafish chr Fugu scaffold174 Tetraodon chr5 Stickleback chrii Medaka chr3 Zebrafish chr6 Xenopus scaffold283 Chicken chr11 Human chr16 Mouse chr8 Check shared syntenies Asip1 Asip Asip2 Agrp2 Agrp1 Agrp

17 Zebrafish Chromosomes agrp2 neighborhood does not share syntenies with teleost agrp1 or with tetrapod Agrp Hsa16 60Mb agrp2 agrp1 AGRP 70Mb Hsa16 Orthologs Medaka Chromosomes Catchen 2009 Genome Research19: Hsa8 agrp2 & asip2 regions show conserved synteny to Hsa8 agrp2 asip2 ripk2 snx16 wwp1 SNX16 WWP1 RIPK2 60Mb 80Mb 100Mb Hsa8 Orthologs Human Chromosomes X Y Ohnologons from vertebrate protochromosome B Nakatani Genome Res 17:1254 ASIP2 region 30Mb Check shared syntenies AGRP ASIP 40Mb Hsa20 Paralogs Braasch (2011) Proc Natl Acad Sci 108:E47-8.

18 Hypothesis 1 fish mouse bkd adapt no adapt gain of TGD function no adapt R2 R1 proto- Asip/Agrp Hypothesis 2 fish mouse bkd adapt no adapt TGD loss of function adapt TGD Old nomenclature teleost asip1 loss tetrapod Asip teleost asip2 teleost agrp2 tetrapod OGM teleost agrp1 loss tetrapod Agrp bony vertebrate OGM Nomenclature in light of evolution asip1 Asip1 asip2a asip2b agrp Agrp Adapting to background could have originated much earlier Braasch (2011) Proc Natl Acad Sci 108:E47-8.

19 Annotation and Nomenclature: An Example: Zebrafish The goal "Nothing in Biology Makes Sense Except in the Light of Evolution" Theodosius Dobzhansky Amer Biol Teach (1973) 35: Genome duplication Gene losses: Ohnologs gone missing Solutions Trees + conserved syntenies S1 S2 g1a g1b G2

20 Annotation and Nomenclature: A Zebrafish Example Julian Catchen Ingo Braasch John Postlethwait