Loss of information at deeper times

Transcription

1 Loss of information at deeper times (and the origin of proteins?) David Penny Brisbane July 2014 The mathematicos caused the problem!!! Now they should solve it! And the origins of protein synthesis Okay, maybe we could help them, Here are some ideas

2 the comfort zone ML Int ML Rel Ml av ML ML an MP ML ML ep MP MP popn classic phylogeny deep phylogeny

3 Markov models - Loss of information can we go further back in time? Mossel and Steel

4 damned eukaryotes!

5 One Eukaryotic Tree crown group Amoebozoa Plantae Chromalveolates Plants Green Algae Red Algae Alveolates fungamals Animals Stramenopiles Radiolaria Rhizaria Fungi Microsporidia Fred or LECA Cercozoa Euglenozoa Heterolobosea Diplomonads Parabasalids Excavates What is common to all groups of modern (extant) eukaryotes? We have pretty good data. We can get solid evidence.

6 Calculated results, Δ ¼ + ne -qt

7 idea 1. simulations (covarion model) percentage of trees correct 120% 100% 80% 60% 40% 20% d=0.001 d=0.100 d=0.500 d=1.000 d=2.000 d=5.000 infinite 0%

8 simulation results with standard model number of internal edges correct, out of 6 neighbor joining, 9 taxa, 1000 columns, i.i.d millions of years (log scale)

9 idea 2, delete fast sites If there were a mixture of a) faster evolving sites, and b) and we could identify them c) and remove them would that help go further back in time?

10 deleting faster sites

11 Ancestral Sequence Reconstruction (idea 3) Giardia animals plants

12 3,4 testing Ancestral Sequence Reconstruction vaults 3-D info

13 subgroups X and Y a x a y a b c d e k l m n o subgroup X subgroup Y

14 chloroplast vs nuclear Data Type Group X Group Y Divergence Times X² d.f. p(x²) X²(con trol) p(x²)(contr ol) Chloro Eudicot Monocot 125mya E E-01 plast Chloro plast Angiosper m Gymnosperm 305mya E E-01 Chloro plast Seed plant Fern 390mya E E-01 Chloro Streptophy Chlorophyta 700mya E E-01 plast ta Chloro plast Red Algae Green Algae ~ 1000mya E E-01 Chloro plast Algae Cyanobacteria ~ 1500mya E E-01 Nuclear Algae Cyanobacteria ~ 1500mya E E-01

15 4. gene length vs similarity

16 5. should we emphasize conserved residues? (or surface ones)

17 6, Weighting i j f 1 a.... a f a.... a. f a..... a f a g 1. a a a a. a a.... g 2 a a a a a.. a.. a. h 1.. a a a... a a.. h 2.. a. a... a a.. h 3 a.. a a... a a.. upper bound = 17 13? lower bound = 12 i j i j... a Would weighting by incompatibilities help? a. a a

18 7, information from sequence order not used Alignment Reordered Alignment original sequence order shuffled/reordered AIIFLNSALGPSPELFPIILATKVL ASAGPSPPATPLLIIIILLFFNEKV AIMFLNSALGPPTELFPVILATKVL ASAGPPTPATPLLIMVILLFFNEKV SIMFLNHTLNPTPELFPIILATETL SHTNPTPPATPLLIMIILLFFNEET TILFLNSSLGLQPEVTPTVLATKTL TSSGLQPPATPLLILTVLVTFNEKT TLLFLNSMLKPPSELFPIILATKTL TSMKPPSPATPLLLLIILLFFNEKT ALLFLNSTLNPPTELFPLILATKTL ASTNPPTPATPLLLLLILLFFNEKT AILFLNSFLNPPKEFFPIILATKIL ASFNPPKPATPLLILIILFFFNEKI c! ways to reorder alignment shuffle by columns & by taxa 8. could we use words of 2, 3, 4, 5, letters 9. Alphabet reduction?

19 damned eukaryotes!

20 the origin of protein synthesis? continuity all intermediates functional can t evolve for what doesn t exist limits of evolutionary mechanisms - no miracles Protein synthesis? mrna, trnas, rrnas, triplet code - why 3?

21 Eigen limit 1 master sequence

22 Eigen limit 2 0 selection mutation

23 Eigen limit 3 0 selection mutation

24 Eigen limit 4 ~1 error per replication, error catastrophe, mutational meltdown 0 selection mutation

25 error rates the error rate limits the length that can be copied, Manfred Eigen (1971) 2 errors in 37 copies of hammerhead ribozyme, 20-fold improvement

26 ribavirin and polio viruses Crotty et al. PNAS 98,

27 synthesis of RNA from cyclic GTPs

28 hydrolysis polymerisation H O H O H O H O H 3 N + C C O - + H 3N + C C O - α α + H 3 N C C N -C C O - + H 2 O α α R } R 2 R 1 R 2 two monomers one dimer (+H 2 O). heat amino acids dry, or drying cycles (fluctuating clay environment) or frozen in ice?

29 RNA evolution - in vitro

30 enzyme efficiency RNA RNP protein CATALYST K cat (min -1 ) K cat /K m (M -1 min -1 ) RNA Tetrahymena L-21(SacI) polynucleotide kinase RNase P RNA x x x 10 6 RNP RNase P RNA + protein x 10 6 protein RNase T1 T4 polynucleotide kinase triose-p isomerase carbonic anhydrase 5,700 25, , ,000, x x x x 10 9 RNA copied by protein, error rate is high

31 origin of protein synthesis?? C NNN B N A N-TP NNN How long would a G=C pairing last?

32 origin of protein synthesis? aa+ inactivated trna D activated trna 3 A C C activated trna aa+ A C aa+ A C C new RNA strand 2 1 NNN template strand activ ated trn A ribozyme-catalysed decoding, cleavage and ligation functions

33 predictions Theoretical/computational time of (say) GC binding is it increased by heavy RNAs di and trinucleotides Experimental length of RNA copied (dinucleotides) amino acid codes???