Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA
description
Transcript of Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA
![Page 1: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/1.jpg)
UNIVERSITAT DE BARCELONA
U
B
Curso de postgradoGENOMICA, PROTEOMICA Y
BIOINFORMATICADESARROLLO DE ESTRATEGIAS TERAPEUTICAS PARA EL NUEVO MILENIO
Enero 2005
Dr. Jordi Garcia Fernàndez Departament de Genètica Facultat de BiologiaUniversitat de Barcelonae.mail: [email protected]
Genómica:Genómica
comparada/evolución del genoma
![Page 2: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/2.jpg)
![Page 3: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/3.jpg)
La paradoxa del valor C, o no es una paradoxa?
![Page 4: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/4.jpg)
Cnidarios
AcelomadosPseudocelomados
Protostomados Celomados
Deuterostomados
TriblásticosBilaterales
Celoma
Simetríabilateral
PoríferosDiblásticos
Las grandes transiciones del Reino Animal
Multi-celularidad
![Page 5: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/5.jpg)
Cnidarios
AcelomadosPseudocelomados
Protostomados Celomados
TriblásticosBilaterales
Celoma
Simetríabilateral
Poríferos
Las grandes transiciones del Reino Animal
Multi-celularidad
Vertebrados
Cresta neural, vértebras
Diblásticos
![Page 6: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/6.jpg)
CnidariosAcelomadosPseudocelomados
Protostomados Celomados
TriblásticosBilaterales
CelomaSimetríabilateral
PoríferosDiblásticos
Las grandes transiciones del Reino Animal
Multi-celularidad Vertebrados
Cresta neural, vértebras
![Page 7: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/7.jpg)
Cnidarios
Protostomados Celomados
TriblásticosBilaterales
SimetríaBilateral y celoma
PoríferosDiblásticos
Las grandes transiciones del Reino Animal
Multi-celularidad Vertebrados
Cresta neural, vértebras
AcelomadosPseudocelomados
![Page 8: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/8.jpg)
Cnidarios
Protostomados TriblásticosBilaterales
SimetríaBilateral y celoma
PoríferosDiblásticos
Las grandes transiciones del Reino Animal
Multi-celularidad Vertebrados
Cresta neural, vértebras
Acelomorfos
Ruiz-Trillo y col, 1999, 2002Jondelius y col., 2002Telford y col., 2003Pasquinelli y col., 2003
CelomaSimetríabilateral
![Page 9: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/9.jpg)
Evolutionary Transitions in Metazoans
Protostomes
Deuterostomes
Origin of Bilaterians
Cambrian Explosion
Origin of Vertebrates
Origin of Metazoan
![Page 10: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/10.jpg)
Ohno, S. (1970) “Evolution by Gene Duplication”
Susumu Ohno1928-2000
Propuso que genes extra (duplicados) son material potencial para incrementar la complejidad
Why?
![Page 11: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/11.jpg)
Ohno, S. (1970) “Evolution by Gene Duplication”
Susumu Ohno1928-2000
Propuso que genes extra (duplicados) son material potencial para incrementar la complejidad
Why? “Only the cistron (gene) which became redundant was able to escape from the relentless pressure of natural selection, and by escaping, it accumulated formerly forbidden mutations to emerge as a new gene locus”
Lo que hoy denominamos NEOFUNCIONALIZACION
![Page 12: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/12.jpg)
Ohno, S. (1970) “Evolution by Gene Duplication”
Susumu Ohno1928-2000
Propuso que genes extra (duplicados) son material potencial para incrementar la complejidad
Why? “natural selection merely modified, while redundancy created”
![Page 13: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/13.jpg)
EVOLUTION BY GENE/GENOME DUPLICATION
ps
A
B
A
AC
AB
Innovation
Innovation + redundancy
Inactivation (pseudogene)
NEW
FUNCTION
AA
A
AA
A
AA
A
![Page 14: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/14.jpg)
Mecanismes de duplicació génicaRecombinació no homòloga
No disjunció meiòtica
![Page 15: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/15.jpg)
El (los) complejo(s) Hox
![Page 16: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/16.jpg)
Duplicació: innovació i redundància
![Page 17: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/17.jpg)
L’origen dels vertebrats:invencions evolutives
![Page 18: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/18.jpg)
amniotes ray-finned fishescyclostomes cephalochordates tunicates
Vertebrados
Cordados
La posición privilegiada de anfioxo
![Page 19: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/19.jpg)
ANFIOXO, LANCETA, CEFALOCORDADOS
Phylum Chordata; Subphylum Cephalochordata
•Género Branchiostoma, 28 especies•Género Epigonichthys, 1 especie•Ampliamente distribuidos en mares templados y tropicales•Adultos en hábitats arenosos•Profundidad 0,5-40? m•Reproducción sexual•Sexos separados
•Tampa (Florida, USA)•Quindao (China)•Banyuls (Francia)
![Page 20: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/20.jpg)
10 years later….
Homeobox gene duplication (1994)
Garcia-Fernàndez & Holland, Nature 1994, Holland et al. Development 1994
![Page 21: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/21.jpg)
Although the analyses are sensitive to the imperfect quality of thegene predictions, our results so far are insuficient to settle whethertwo rounds of WGD occurred around 500 Myr ago. It may bepossible to resolve the issue by systematically estimating the time ofeach of the many gene duplication events on the basis of sequencedivergence, although this is beyond the scope of this report. Anotherapproach to determining whether a widespread duplicationoccurred at a particular time in vertebrate evolution would be tosequence the genomes of organisms whose lineages diverged fromvertebrates at appropriate times, such as amphioxus.
![Page 22: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/22.jpg)
Grups de paralogia, sintènia conservada
![Page 23: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/23.jpg)
2R
1. Origen dels metazous1. Origen dels metazous
2. Origen dels Bilateris2. Origen dels Bilateris
3. Explosió Cámbrica3. Explosió Cámbrica
![Page 24: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/24.jpg)
2R a l‘origen dels vertebrats, R en els peixos teleostis
![Page 25: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/25.jpg)
2001 Dec 2002
De qui son quins gens? Comparant l’home i el ratolí
![Page 26: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/26.jpg)
2000
2001
2002
![Page 27: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/27.jpg)
2002
Ratolí / home
2004
Peix / home
![Page 28: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/28.jpg)
![Page 29: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/29.jpg)
Els genomes humà i murí:bricolatge cromosòmic
NCBI 2003
![Page 30: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/30.jpg)
Paralogia dins de paralogia, i mes sintènia…?
![Page 31: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/31.jpg)
![Page 32: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/32.jpg)
El (los) complejo(s) Hox
![Page 33: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/33.jpg)
Origen y evolución de los complejos Hox y ParaHox
UrProtoHox gene
Hox-like cluster segmental TANDEM duplication
Evx/Mox ancestor
Coupled Hox-like cluster Primordial Hox cluster + EvxPrimordial ParaHox cluster + Mox
Coupled Hox-like cluster BREAKAGE
Primordial ParaHox cluster Primordial extended Hox cluster (Mox + Primordial Hox + Evx)
Ancestral Hox-like cluster(ProtoHox cluster + Evx/Mox ancestor )
UrProtoHox-like
ParaHox cluster (origin of vertebrates) Extended Hox cluster (origin of vertebrates)
ParaHox A
ParaHox B
ParaHox C
ParaHox D
Hox A
Hox B
Hox C
Hox D
Vertebrate duplicationsVertebrate duplications
![Page 34: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/34.jpg)
![Page 35: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/35.jpg)
AP/DV eMS BGaNS EX
CNIDARIA
Acoelomorpha
Hox y Eubilateria (transicions)
L
E
DBilateralitat Celoma
Baguñà, 2002
![Page 36: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/36.jpg)
AP/DV eMS BGaNS EX
CNIDARIA
Acoelomorpha
Hox y Eubilateria (hipòtesi)
PG3 Central Posterior
1/2 9/13
Anterior
Evx
Gsh Cdx Mox
L
E
D
PG3 Central Post
1 2 3 4 5 6/8 9/13 Evx
Gsh 3 Cdx MoxE/MAnterior
Gsh
PG3 Central Posterior
1/2 9/13
Anterior
Evx
Cdx MoxXlox
2 Hox (A+P)2 ParaHox (A+P)
+ 2 HOX + 1 ParaHox Expansió Hox central 1 3
Garcia-Fernàndez, Hereddity (en prensa)
![Page 37: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/37.jpg)
AP/DV eMS BGaNS EX
CNIDARIA
Acoela
Transicions
L
E
D
Multicelularitat
Simetría
PORIFERA
ProtoHox?
![Page 38: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/38.jpg)
CNIDARIA
Acoela
Perspectives
L
E
D
Multicelularidad
Simetría
PORIFERA
CHOANOFLAGELLATA
eMSAP/DV BGaNS EX
![Page 39: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/39.jpg)
Comunicación celularcombinatoria de dominios
King & Carroll, 2001
King et al., 2003
![Page 40: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/40.jpg)
Grandes transiciones del Reino Animal
D
CNIDARIA
Acoela
L
E
PORIFERA
eMSAP/DV BGaNS EX
CHOANOFLAGELLATA
Simetría
Bilateria
Eubilateria
Vertebrados
Multicelularidad
![Page 41: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/41.jpg)
Grandes transiciones del Reino Animal
D
CNIDARIA
Acoela
L
E
PORIFERA
eMSAP/DV BGaNS EX
CHOANOFLAGELLATA
Nemertodermatida
Multicelularidad
Simetría
Bilateria
Eubilateria
Vertebrados
![Page 42: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/42.jpg)
Cys-cluster
Leu-rich motif
Cys-cluster
Cys-cluster
Leu-rich motif
Cys-cluster
N-terminal
extension
Ror-like
Cys domains
Kringle
domainIgG-C2 IgG-C2
IgGV
IgG-C2
Extracelular
Intracelular
TrkA
TrkB
TrkC
Ltrk Dror/Dnrk Dofftrk
TK TK TK TK
Kesteren et al, 1999
AmphiTrk
-C2
-
-Cys cluster
Leurich motif
Cyscluster
IgG
TK
-
Caracterización Estructural de AmphiTrk
![Page 43: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/43.jpg)
TrkA/TrkB/TrkC
AmphiTrkAmphiTrk
Cysteine Cluster
Leucine Rich Region
IgG-C2 domain 1
IgG-C2 domain 2
Tyrosine Kinase domain
Transmembrane domain
Domain shuffling, exon shuffling?
“Promiscuity” mini-exon9
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Shc/SNT tansduction domain
1 2 3 4 5 6-7 8 9-10 11-12 13-14 15 16 17
![Page 44: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/44.jpg)
Modulos/Kits/Redes/GRN
![Page 45: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/45.jpg)
![Page 46: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/46.jpg)
PDX1MED
HNF1bNeuroD-E2A
Ngn3-E2A
Nkx2.2
Nkx6.1
HNF6
HNF1
FoxA2
FoxA3
Isl1
HNF4
FoxA1
FoxO1
Pax6Pax4
Gli2
Hes1
Notch2Notch1
Jagged1 Dll1
mafA < =? >
Ptf1a
MIST1
nr5a2
Insulin Glucagon Brn4
Amylase
Regulatory interactions during pancreatic developmentRegulatory interactions during pancreatic development, by Jan Jensen. Barbara Davis Center for Childhood Diabetes, U. Colorado Health Sciences Center.
HlxB9
Pbx1
Pax2
PDX1HIGH
Sox9
Sox17 Prox1
Shh
Gut
Six3
L-Maf
Eye
Eye
Eye
FoxA2
Eye
HNF1
Exocrine Transcription
Alpha-cell TranscriptionBeta-cell Transcription
GATA4
Cdx2
IFABPIntestinal Transcription
GATA6
CasanovaMixer/Bon
Nodal
ENDODERM
C/EBP-
CellcycleExit
Oct4
Comment on auto-regulation arrows:Green: The gene acts by a self-sustainable mechanism – intrinsic stability of networkRed: The gene may act by a threshold mechanism – intrinsic instability of network
Suc/Isom.
Cdx1Wntcat.
X.L
Z.F
Z.FZ.F
Jagged2
Notch signaling
Pancreas Determination
Activin or nrfX.L
Pax4
Hex
SMAD1/SMAD4
BMP
Pancreas
Documented interaction, positiveDocumented interaction, negative
AutoregulationSuggested interaction, not provenExtra-cellular signaling
Z.F
X.L
Link demonstrated in ZebrafishLink demonstrated in Xenopus LaevisDocumented interaction, not in pancreas
?
Hyperlink, review on subject
Symbols
??
COUP-TFII
LIVER TRANSCRIPTION
?
?
FGF10Indirectly
?
Eye
HNF4
Core Endodermal program
Hyperlink, description of targeted mutation of gene
/SMAD4/
How to use this file:
1. Download file to disk. 2. Open File by double clicking. Select “slideshow” option in
PowerPoint (PC: press F5). Within the slideshow, point-and-click on arrow, gene, or
symbol for exiting to hyperlinked information. Hyperlink information will display when
hovering over symbol. Clicking within non-linked areas will terminate the slideshow. Press
F5 to resume slideshow. For best results, a 17’’ screen, or larger, is recommended.
Comment on targeted mutation links:Studies of the genes by targeting mutations may have been performed by several independent groups, and several publications may exist regarding a particular gene. Furthermore, independent targeting may have been performed, as is the case for e.g. Pdx1, HB9, Ptf1a, NeuroD. Here, each link branches out only to one given study. Please consult the text for additional information to other references having provided information about the role of the gene in pancreatic development using a targeted mutation approach.
Via nkx2.2?SMAD2/SMAD4/SMAD4
Via Sox17 or Mix?
Gut
Gut
GutGut
Endoderm Establishment
Also involving most members of the core endodermal program
Endocrine fate Allocation
![Page 47: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/47.jpg)
1.- Invención de dominios proteicos2.- Ensamblaje de dominios proteicos
-exon shuffling-duplicación intragénica
3.- Creación de redes génicas4.- Redes génicas complejas
-duplicación de redes-conexiones entre redes
Niveles de complejidad en la evolución génica ygenómicaAntonio García-Bellido
Duplicación génica /Regulació génica (co-opció)
![Page 48: Curso de postgrado GENOMICA, PROTEOMICA Y BIOINFORMATICA](https://reader036.fdocuments.co/reader036/viewer/2022062322/568146b6550346895db3daa8/html5/thumbnails/48.jpg)
Genòmica comparada• conservació de grans regions genòmiques en diferents organismes (conservació de la sintènia)• evolució del genoma/bricolatge genòmic• duplicacions i poliploiditzacions• Complexitat del genoma/complexitat de l’organisme • Inferències a partir de sintènia• Sintènia del genoma ancestral• Reordenaments desprès de la duplicació• %Perdua/Divergència gènica
Evidència de duplicacions genòmiques-Saccharomyces cerevisae-origen dels vertebrats-Llinatges particulars
-Xenopus-Teleòstis-Planàries
-Llinatges de plantes