Современное состояние геномики и биоинформатики бактерий

1. Современное состояние геномикии биоинформатики бактерий Краткий обзор направлений исследований

2. http://wishart.biology.ualberta.ca/BacMap/ Black Death It may have reduced world population from an estimated 450 million to between 350 and 375 million in 1400.

4. Полезная статистика

5. >2000 бактерий и архей

6. G E N O M E S I Z E

8. Estimates of genome sizes, based on data from DOGS http://www.cbs.dtu.dk/databases/DOGS/

10. GC content

11. http://esper.lab.nig.ac.jp/study/genome/?page=genome_composition_database_species_listhttp://esper.lab.nig.ac.jp/study/genome/?page=genome_composition_database_species_list В том числе - Eubacteria (1043 species), Archaea (84 species)

12. 2010

15. Selection Forces Genetic Code S N Val GTC Synonymous Change Nonsynonymous Change Ala GCC Val GTG

16. dN= # nonsynonymous substitutions/# nonsynonymous sites dS= # synonymous substitutions/# synonymous sites Test for selection by comparing dN and dS dN/dS= 1: Neutral evolution dN/dS< 1: Purifying selection dN/dS> 1: Positive selection The dN/dS ratio () measures the selective pressure

17. six strains of Escherichia coli and Shigellaflexneri, including five strains that are human pathogens. Beta barrel porins are pore proteins in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Their structure has been thoroughly described elsewhere. They allow the passage of small, hydrophilic, or charged molecules; however, porins are also important in interactions with the host immune system and in pathogenesis. Furthermore, they serve as receptors for phages, antibiotics, and colicins. 2007

19. Molecular Clock • The molecular clock hypothesis was put forward by Zuckerkandl and Pauling in 1962. • They noted that rates of amino acid replacements in animal hemoglobins were proportional to time of divergence—as judged from the fossil record.

20. Evidence for Rate Constancyin Hemoglobin from Zuckerkandl and Pauling (1965)

21. TheMolecular Clock Hypothesis • Amount of genetic difference between sequences is a function of time since separation. • Rate of molecular change is constant (enough) to predict times of divergence

22. Rate Constancy? Page & Holmes p240

23. Rate Heterogeneity • Rate of molecular evolution can differ between • nucleotide positions • genes • genomic regions • genomes within species (nuclear vs organelle) • species • over time • If not considered, introduces bias into time estimates

24. Relative rate tests have shown that there is no universal molecular clock.However, sufficiently accurate local clocks may exist.

25. slow fast Rate of evolution

26. Mutation rate per site per year versus genome size (Gago S, Elena SF, Flores R, Sanjuán R. Extremely high mutation rate of a hammerhead viroid. 2009. Science 323:1308.)

27. PNAS 1999 diNucleotide Relative Frequencies

29. Chaos Game Representation

31. Bacterial Replication

34. DNA replication https://www.youtube.com/watch?v=4jtmOZaIvS0

35. GC skews - Асимметрия по стрендам GC Skew = (G - C)/(G + C)

36. GC 3 позиция

37. Правила Чаргаффа (Chargaff’s rules) • Геном человека • A=30.9% and T=29.4%; G=19.9% and C=19.8% • 1ое правило Чаргаффа • А=Т и G=C в двуцепочечной ДНК • 2ое правило Чаргаффа • А=Т и G=C в одноцепочечной ДНК http://www.youtube.com/watch?v=HvJlnujmYcg

38. ДНК-блуждание (DNA walk) Bacillus_anthracis_Ames Aquifex_aeolicus Salmonella_enterica_Choleraesuis Drosophila chr2 Y chromosome human (genes) Sacharamaceae cerevisae

39. 2009

40. Figure 1. 2D DNA graphs of all genes from a chromosome for different organisms. Poptsova MS, Larionov SA, Ryadchenko EV, Rybalko SD, et al. (2009) Hidden Chromosome Symmetry: In Silico Transformation Reveals Symmetry in 2D DNA Walk Trajectories of 671 Chromosomes. PLoS ONE 4(7): e6396. doi:10.1371/journal.pone.0006396 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006396

41. Figure 2. Relations between number, cumulative gene length, GC and AT skews of genes from different strands. Poptsova MS, Larionov SA, Ryadchenko EV, Rybalko SD, et al. (2009) Hidden Chromosome Symmetry: In Silico Transformation Reveals Symmetry in 2D DNA Walk Trajectories of 671 Chromosomes. PLoS ONE 4(7): e6396. doi:10.1371/journal.pone.0006396 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006396

42. Сравнительная геномикаComparative Genomics • Сравнение по генам • По кускам генома или по целому геному • По РНК-структурам

43. Полногеномные сравнения

44. Multiple genome alignment performed using Mauve software and the chromosomes of A. oleivorans DR1, A. baylyi, A. calcoaceticus, and A. baumannii. Jung J et al. Appl. Environ. Microbiol. 2011;77:7418-7424

45. Figure 2. Genomic overview of the similarity between completely sequenced Wolbachia strains. Ellegaard KM, Klasson L, Näslund K, Bourtzis K, et al. (2013) Comparative Genomics of Wolbachia and the Bacterial Species Concept. PLoS Genet 9(4): e1003381. doi:10.1371/journal.pgen.1003381 http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003381

46. Сравнительная геномика на уровне генов Задача отобра ортологови паралогов Ortholog databases: http://questfororthologs.org/

47. Figure 2 The bacterial pan-genome. Each gene found in the bacterial genome represents one of three pools: genes found in all but a few bacterial genomes comprise the extended core of essential genes (?250 gene families that encode proteins involved in tran... Trends in Genetics Volume 25, Issue 3 2009 107 - 110

48. RNA world http://www.lifesorigin.com/chap10/rna_world.php