A biológia néhány megválaszolatlan nagy kérdése

1. A biológia néhány megválaszolatlan nagy kérdése Szathmáry Eörs ELTE Biológiai Intézet

2. Theodosius Dobzhansky (1900-75) • „A biológiában minden csak az evolúció fényében nyer értelmet” • Mi? • Hogyan? • Miért?

3. Az evolúció egységei Vannak olyan öröklődő bélyegek, melyek a termékenységre és/vagy a túlélőképességre hatnak • sokszorozódás • öröklődés • változékonyság

4. A replikáció eredete? • Kémiai szempontból mindig autokatalízist igényel • A legegyszerűbb forma: A + X  2 A + Y • A biológia számára kiemelt jelentőségű • Sokkal általánosabb, mint a DNS-replikáció

5. A formóz ‘reakció’ formaldehid autokatalízis glikolaldehid Butlerow, 1861

6. Replikáció a formóz reakcióban • Nem-információs replikáció • Autokatalízis – IGEN • Öröklődés – NEM • Jó az anyagcseréhez • Nem jó genetikai célokra

7. A fordított citrát-kör korai eredete? • Günter Wächtershäuser (1990) • CO2-fixálás pirit-felszíneken, a mélytengeri hévforrásoknál • Nincs rá bizonyíték

8. Az élet keletkezésének a fő problémája a metabolitok kellő kanalizásása a lehetséges reakciók terében • Az enzimek a fontos reakciókat a kellemetlen reakciókhoz képest gyorsítják • A spontán mellékreakciók száma rendkívül nagy • A fenntartás, nemcsak a szaporodás, feltétele az autokatalízis dx/ dt = k x – d x = 0

9. Minden, a mellékreakciókat elhanyagoló „hálózati” modell bűnösen csökött • Pl. a Kauffman által javasolt fehérje-hálózatok • A modellekben általában azt feltételezik, hogy a lehetséges reakciók vagy előnyösek, vagy semlegesek • Egy kémiai „kanyonból” jött ki az élet?

10. A kémiai evolúció az élet kialakulása és a kátrány képződése közötti verseny volt Kémiai hálózatok Kátrány Élet A bolygók hanyad részén lenne végül csak kátrány?

11. 1986: az első mesterséges replikátor És mi van, ha hosszabb?

12. Kísérlet és elmélet nemes versenye

13. Esetleg hőmérsékleti oszcillációval?

14. A spontán hosszabbodás gátolja a replikációt!

15. The extended genetic alphabet

16. New base pair in the code for new amino acid Implementation with isoC:isoG pair UAG nonsense codon for iodotyrosine Or the (iso-C)AG codon Challenge: coupling of non-standard amino acids to nonstandard tRNAs by nonstandard synthetases

17. Fisher’s(1930) question "No practical biologist interested in sexual reproduction would be led to work out the detailed consequences experienced by organisms having three or more sexes; yet what else should he do if he wishes to understand why the sexes are, in fact, always two?"

18. The fitness of ribo-organisms W(N) = A(N) Q(N) (vö. Eigen, 1971) W fitness A reproduction rate Q fidelity of replication N size of the alphabet

19. W(N) = A(N) Q(N) There is somewhere an optimal N

20. Mi hajtotta a kambriumi robbanást?

21. A „robbanás”

22. Before the Cambrian… Cnidaria were some of the earliest fossils recognized as animals. This death assemblage of Vendian cnidarians (medusoids) predate the Cambrian Explosion by tens of millions of years. These jellyfish-like examples of Nemaia simplex are relatively attributable to jellyfish descendants alive today. The incredible soft-bodied preservation is believed to be the result of impressions made in a microbial mat contained within the sand, a phenomenon that is exceedingly rare in the fossil record.

23. Temporal distribution (bars) and stratigraphic occurrences (black dots) of representative Ediacara genera, plotted against timescale of Ediacaran Period and fossil localities or stratigraphic units. The three Ediacara assemblages (Box 1) are indicated by different shades of gray. The Marinoan and Gaskiers glaciations, as well as the age range of the Doushantuo biota, are also marked.

25. Explanations Environmental Explanations The accumulation of enough oxygen to sustain large animals, large-scale and environmental change that occurred at about the time of the initiation of the radiation. • the geological evidence that points to the Snowball Earths • the large negative carbon isotopic anomaly at the precambrian/Cambrian boundary, followed by a period ofunusual volatility, (c) paleomagnetic evidence for true polar wander (whereby, on geological timescales, the continents rapidly shifted their positions).

26. Explanations II. Developmental Explanations • A small kit of key developmental genes was used in a new flexible way and generated the Cambrian diversity. • Dynamical patterning modules (units that mobilize physical processes characteristic of chemically and mechanically excitable meso- to macroscopic systems such as cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on lateral inhibition and multistable and oscillatory dynamics) generated all the body plans that emerged in the Cambrian. • Stress due to climatic and chemical changes (snow ball earths) could have activated stress-managing genes (such as the gene coding for Hsp90) leading to great increase in variation. • miRNA may be involved: it is present in eumetazonas and is absent in basal groups that lack organs including sponges, cnidarians, and acoel flatworms

27. Several workers point to the origin of the bilaterian developmental system, including the origin of the Hox genes, etc., as the primary cause of the origin of the bilaterian developmental “explosion”

28. ‘Dynamical patterning modules (DPMs)generated the multicellular forms during the explosive radiation of animal body plans in the middle Cambrian, approximately 530 million years ago; multicellular organisms could have explored an extensive morphospace without concomitant genotypic change or selection for adaptation.

29. A role for miRNA??? (Peterson) A core set of microRNAs is conserved in animal with organs (protostomes and deuterostomes), but is absent in basal groups that lack organs including sponges, cnidarians, and acoel flatworms.  In addition, the continuous acquisition and fixation of miRNAs in various animal groups strongly correlates both with the hierarchy of metazoan relationships (A) and with the non-random origination of metazoan morphological innovations through geologic time.  This suggests that microRNAs could have played a pivotal role in evolution of both animal body plans and morphological complexity (B), with organs being the ultimate manifestation of this innovation.  And because microRNAs regulate tens to hundreds of protein-coding genes, they may also constrain the future evolution of animal taxa (C bottom).

30. Animal miRNAs and morphological complexity Trichoplax • Oikopleura: urchordate

31. Tissue-specific miRNA expression in the bilaterian ancestor

32. miRNA expression onset is coupled to differentiation

33. miRNA and siRNA systems

34. Animal miRNA biogenesis

35. Plant miRNA biogenesis

36. Earliest possible stages of evolution of the eukaryotic RNAi proteinmachinery

37. Prokaryotic connections

38. Origin of eukaryotic miRNA machinery • Comparative genomic analysis shows that the protein machinery of RNAi is conserved in allmajor eukaryotic lineages, independent loss in many unicellular forms notwithstanding. • It appears most likely that LECA possessed relatively complex RNAi machinery. At aminimum, this primordial RNAi machinery consisted of an Argonaute-like protein, a Piwi-likeprotein, a Dicer, and an RNA-dependent RNA polymerase. • Comparison of these proteins withtheir prokaryotic homologs suggests that, during eukaryogenesis, the protein machinery ofRNAi was pieced together from archaeal, bacterial and phage proteins that performed diversefunctions in DNA repair and RNA processing, unrelated to RNA interference.

39. Origin of miRNAs from genomic repeats or transposable elementsin animals

40. Explanations III Ecological explanations – arms races Evolution of predation Hard body parts The Eye The nervous system Associative learning

41. Andrew Parker : In the Blink of an Eye 2003. Perseus Books Parker suggests that the Cambrian explosion was caused by the development of the eye, an organ that not only senses light, but can see an image. He states that the trilobite evolved its eye about 543 million years ago, which would have been in time to help ignite the Cambrian explosion. Once eyes developed, there would have been a revolution in predation. According to Parker, the period before the Cambrian ''was rather an experimental stage for predation, occupied mainly by peace-loving vegetarians that were willing enough to accept any occasional animal matter they stumbled upon.'' But once the ''light switch'' was turned on, the randomness of the hunt was gone. Since every animal could be seen -- predators included -- the rules of survival changed. ''So to adapt to vision,'' Parker writes, ''an animal must evolve a response in terms of adapting its visual appearance, whether it is warning shapes and colours, camouflage or hiding behind physical barriers.''

42. The Eye? Illustration of a possible evolutionary path for the development of the basic eye typesAndre

44. Classical (Pavlovian) conditioning: a neutral stimulus is paired with a primary stimulus which elicits a specific response (the response to this stimulus in either inborn, or was learnt earlier). The neutral stimulus is neutral with respect to this specific response, and precedes the primary stimulus. An animal that exposed to the paired stimuli will first respond to the primary stimulus, but later will respond to the neutral stimulus alone. Pavlov presented dogs with food, and measured their salivary response (how much they drooled). Then he began ringing a bell just before presenting the food. At first, the dogs did not begin salivating until the food was presented. After a while, however, the dogs began to salivate when the sound of the bell was presented. They learned to associate the sound of the bell with the presentation of the food.

45. Cubozoa

46. Increased size required better motor and sensory coordination and neural integration, and was associated with bigger, metabolically-expensive brains and ganglia. Active life-span was probably extended, so learning the associations among cues became worthwhile. The initial stages of associative learning evolution may have required only very simple modifications in the threshold concentrations of molecules that strengthened synaptic connections between newly-linked, co-activated neurons.