Un dels fets més remarcables del nostre planeta és que, a diferencia de tots els altres planetes que coneixem en l’actualitat, és curull de vida. Si ens centrem en els animals, es calcula que actualment a la Terra hi ha entre 1 i 20 milions d’espècies, les quals probablement representen menys de l’1% de totes les que han existit. Tanmateix, potser sigui encara més sorprenent que absolutament tota aquesta diversitat animal –anèlids i pinsans, papallones i escurçons, orades i meduses, mosques i persones– descendim d’un avantpassat comú que va viure als mars durant l’era Precambriana, fa més de 540 milions d’anys.
L'explicació de tota aquesta diversitat rau, sens dubte, en l'evolució, en els processos dinàmics de canvi i selecció de les espècies. L'any 1977, Stephen J. Gould va publicar un llibre que ha resultat cabdal en la història de la biologia, Ontogènia i filogènia, en el qual justificava perquè la biologia del desenvolupament i l'evolució, dues disciplines centrals de la biologia que havien anat divergint durant els dos primers terços del segle XX, havien de trobar un marc comú de treball, dins el quals els seus respectius conceptes bàsics poguessin ser compresos i compartits, en benefici mutu.
A partir de 1980 es va fer evident que els animals no només compartim gens similars pel que fa al control del nostre desenvolupament sinó també molts altres aspectes més generals de la nostra ontogènia –del nostre desenvolupament–. Tots els avenços que s'han produït en aquest sentit han obert la porta a la comprensió molecular del desenvolupament, i l'anàlisi de l'expressió d'aquests gens en un nombre creixent d'espècies ha permès correlacionar les activitats gèniques amb els canvis evolutius.
Aquest és el substrat conceptual de l'evo-devo, una disciplina científica que reuneix dins un mateix marc conceptual els coneixements sobre l'evolució i el desenvolupament embrionari, i que no només els integra sinó que els dota del seu màxim significat. Però no avancem esdeveniments, perquè l’objectiu d’aquests seminaris és desgranar de forma progressiva la contribució de l’evo-devo a la comprensió que actualment tenim dels processos evolutius en els animals, inclosa la nostra espècie. Primer farem una breu introducció històrica a aquesta disciplina científica, la qual parteix dels estudis embriològics i evolutius clàssics. Segon, ens endinsarem en els conceptes bàsics de la genètica i l’embriologia, en la caixa d’eines moleculars (developmental genetic toolkit) que ha permès l’evolució de les múltiples i diverses morfologies en el grup dels animals, la qual ens permetrà entendre els exemples d’evo-devo que s’utilitzaran a continuació i ens ajudarà a copsar la importància i les aportacions d’aquesta disciplina científica. A partir d’uns exemples concrets -l’estudi dels mecanismes genètics de les extremitats dels insectes [1, 2], dels becs dels pinsans de Darwin [3] i de l’evolució de les ales dels ratpenats [4] ens ajudarà a entendre cóm i quins canvis genètics poden alterar el desenvolupament i la morfologia dels disseny corporal. Discutirem l’impacte que la dinàmica de l’evolució dels gens i genomes en l’evolució animal [5], destacant la rellavància de l’evolució dels mecanismes d’splicing [6]. I aprofundirem com l’era de la genòmica està permetent explorar la diversitat animal, fent servir com exemple la seqüenciació del genoma complert d’una medusa [7] i com la seva comparació amb la d’altres organismes bilaterals [8], ens ha permès descobrir l’antiguitat de la majoria de gens que formen tots els animals, incloent l’home.
A TREBALLAR:
3 de maig
Introduction to Evo-Devo, by Dr. Cristian Cañestro
10 de maig
Article 1. (màxim 2 persones)
Evolution of a transcriptional repression domain in an insect Hox protein
Galant R, Carroll SB
Nature 2002, 415(6874):910-913.
Homeotic (Hox) genes code for principal transcriptional regulators of animal body regionalization. The duplication and divergence of Hox genes, changes in their regulation, and changes in the regulation of Hox target genes have all been implicated in the evolution of animal diversity. It is not known whether Hox proteins have also acquired new activities during the evolution of specific lineages. Amino-acid sequences outside the DNA-binding homeodomains of Hox orthologues diverge significantly. These sequence differences may be neutral with respect to protein function, or they could be involved in the functional divergence of Hox proteins and the evolutionary diversification of animals. Here, we identify a transcriptional repression domain in the carboxy-terminal region of the Drosophila Ultrabithorax (Ubx) protein. This domain is highly conserved among Ubx orthologues in other insects, but is absent from Ubx in other arthropods and onychophorans. The evolution of this domain may have facilitated the greater morphological diversification of posterior thoracic and anterior abdominal segments characteristic of modern insects.
Comment: Wray GA: Evolution: spot on (and off). Nature 2006, 440:1001
Review: Wray GA: The evolutionary significance of cis-regulatory mutations. Nat Rev Genet 2007, 8:206
Article 2. (màxim 2 persones)
Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene.
Prud'homme B, Gompel N, Rokas A, Kassner VA, Williams TM, Yeh SD, True JR, Carroll SB Nature 2006, 440(7087):1050-1053.
The independent evolution of morphological similarities is widespread. For simple traits, such as overall body colour, repeated transitions by means of mutations in the same gene may be common. However, for more complex traits, the possible genetic paths may be more numerous; the molecular mechanisms underlying their independent origins and the extent to which they are constrained to follow certain genetic paths are largely unknown. Here we show that a male wing pigmentation pattern involved in courtship display has been gained and lost multiple times in a Drosophila clade. Each of the cases we have analysed (two gains and two losses) involved regulatory changes at the pleiotropic pigmentation gene yellow. Losses involved the parallel inactivation of the same cis-regulatory element (CRE), with changes at a few nucleotides sufficient to account for the functional divergence of one element between two sibling species. Surprisingly, two independent gains of wing spots resulted from the co-option of distinct ancestral CREs. These results demonstrate how the functional diversification of the modular CREs of pleiotropic genes contributes to evolutionary novelty and the independent evolution of morphological similarities.
Comment: Levine M: How insects lose their limbs. Nature 2002, 415:848
17 de maig
Article 3. (màxim 2 persones)
Bmp4 and morphological variation of beaks in Darwin's finches.
Abzhanov A, Protas M, Grant BR, Grant PR, Tabin CJ
Science 2004, 305(5689):1462-1465.
Darwin's finches are a classic example of species diversification by natural selection. Their impressive variation in beak morphology is associated with the exploitation of a variety of ecological niches, but its developmental basis is unknown. We performed a comparative analysis of expression patterns of various growth factors in species comprising the genus Geospiza. We found that expression of Bmp4 in the mesenchyme of the upper beaks strongly correlated with deep and broad beak morphology. When misexpressed in chicken embryos, Bmp4 caused morphological transformations paralleling the beak morphology of the large ground finch G. magnirostris.
Article 4. (màxim 3 persones)
Regulatory divergence modifies limb length between mammals.
Cretekos CJ, Wang Y, Green ED, Martin JF, Rasweiler JJt, Behringer RR
Genes Dev 2008, 22(2):141-151.
Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus
with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis-regulatory redundancy may facilitate accumulation of such mutations.
Comment: Weatherbee SD: Mammalian limbs take flight. Dev Cell 2008, 14:149.
24 de maig
Article 5 (màxim 3 persones)
Impact of gene gains, losses and duplication modes on the origin and diversification of vertebrates.
Cañestro C, Albalat R, Irimia M, Garcia-Fernàndez J.
Semin Cell Dev Biol. 2013 Feb;24(2):83-94
The study of the evolutionary origin of vertebrates has been linked to the study of genome duplications since Susumo Ohno suggested that the successful diversification of vertebrate innovations was facilitated by two rounds of whole-genome duplication (2R-WGD) in the stem vertebrate. Since then, studies on the functional evolution of many genes duplicated in the vertebrate lineage have provided the grounds to support experimentally this link. This article reviews cases of gene duplications derived either from the 2R-WGD or from local gene duplication events in vertebrates, analyzing their impact on the evolution of developmental innovations. We analyze how gene regulatory networks can be rewired by the activity of transposable elements after genome duplications, discuss how different mechanisms of duplication might affect the fate of duplicated genes, and how the loss of gene duplicates might influence the fate of surviving paralogs. We also discuss the evolutionary relationships between gene duplication and alternative splicing, in particular in the vertebrate lineage. Finally, we discuss the role that the 2R-WGD might have played in the evolution of vertebrate developmental gene networks, paying special attention to those related to vertebrate key features such as neural crest cells, placodes, and the complex tripartite brain. In this context, we argue that current evidences points that the 2R-WGD may not be linked to the origin of vertebrate innovations, but to their subsequent diversification in a broad variety of complex structures and functions that facilitated the successful transition from peaceful filter-feeding non-vertebrate ancestors to voracious vertebrate predators.
Article 6. (màxim 2 persones)
Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats.
Gracheva EO, Cordero-Morales JF, González-Carcacía JA, Ingolia NT, Manno C, Aranguren CI, Weissman JS, Julius D.
Nature. 2011 Aug 3;476(7358):88-91
Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their sanguinary lifestyle. Chief among such adaptations is the ability to detect infrared radiation as a means of locating hotspots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons and pit vipers are capable of detecting infrared radiation. In each case, infrared signals are detected by trigeminal nerve fibres that innervate specialized pit organs on the animal's face. Thus, vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species-specific or cell-type-specific manner. Previously, we have shown that snakes co-opt a non-heat-sensitive channel, vertebrate TRPA1 (transient receptor potential cation channel A1), to produce an infrared detector. Here we show that vampire bats tune a channel that is already heat-sensitive, TRPV1, by lowering its thermal activation threshold to about 30 °C. This is achieved through alternative splicing of TRPV1 transcripts to produce a channel with a truncated carboxy-terminal cytoplasmic domain. These splicing events occur exclusively in trigeminal ganglia, and not in dorsal root ganglia, thereby maintaining a role for TRPV1 as a detector of noxious heat in somatic afferents. This reflects a unique organization of the bat Trpv1 gene that we show to be characteristic of Laurasiatheria mammals (cows, dogs and moles), supporting a close phylogenetic relationship with bats. These findings reveal a novel molecular mechanism for physiological tuning of thermosensory nerve fibres
31 de maig
Article 7. (màxim 2 persones)
Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization.
Putnam NH, Srivastava M, Hellsten U, Dirks B, Chapman J, Salamov A, Terry A, Shapiro H, Lindquist E, Kapitonov VV et al.
Science 2007, 317(5834):86-94.
Sea anemones are seemingly primitive animals that, along with corals, jellyfish, and hydras, constitute the oldest eumetazoan phylum, the Cnidaria. Here, we report a comparative analysis of the draft genome of an emerging cnidarian model, the starlet sea anemone Nematostella vectensis. The sea anemone genome is complex, with a gene repertoire, exon-intron structure, and large-scale gene linkage more similar to vertebrates than to flies or nematodes, implying that the genome of the eumetazoan ancestor was similarly complex. Nearly one-fifth of the inferred genes of the ancestor are eumetazoan novelties, which are enriched for animal functions like cell signaling, adhesion, and synaptic transmission. Analysis of diverse pathways suggests that these gene "inventions" along the lineage leading to animals were likely already well integrated with preexisting eukaryotic genes in the eumetazoan progenitor.
Comment: Pennisi E: Sea anemone provides a new view of animal evolution. Science 2007, 317:27
Article 8. (màxim 3 persones)
Evo-devo: variations on ancestral themes.
De Robertis EM
Cell 2008, 132(2):185-195.
Most animals evolved from a common ancestor, Urbilateria, which already had in place the developmental genetic networks for shaping body plans. Comparative genomics has revealed rather unexpectedly that many of the genes present in bilaterian animal ancestors were lost by individual phyla during evolution. Reconstruction of the archetypal developmental genomic tool-kit present in Urbilateria will help to elucidate the contribution of gene loss and developmental constraints to the evolution of animal body plans.
