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Современное состояние геномики и биоинформатики бактерий Краткий обзор направлений исследований.

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Presentation on theme: "Современное состояние геномики и биоинформатики бактерий Краткий обзор направлений исследований."— Presentation transcript:

1 Современное состояние геномики и 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.

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4 Полезная статистика

5 >2000 бактерий и архей

6 GENOMESIZEGENOMESIZE

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

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10 GC content

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

12 2010

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15 Selection Forces Genetic Code Val GTC Val GTG Ala GCC Synonymous Change Nonsynonymous Change SN

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

17 six strains of Escherichia coli and Shigella flexneri, including five strains that are human pathogens. 2007 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.

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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 Constancy in Hemoglobin from Zuckerkandl and Pauling (1965)

21 The Molecular 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 Page & Holmes p240 Rate Constancy?

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

25 25 fastslow Rate of evolution

26 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

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29 Chaos Game Representation

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31 Bacterial Replication

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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) 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 Геном человека A=30.9% and T=29.4%; G=19.9% and C=19.8%

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

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 геномика Comparative 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 ортологов и паралогов http://questfororthologs.org/ Ortholog databases:

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

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51 tRNA

52 Transcription and translation https://www.youtube.com/watch?v=41_Ne5mS2ls

53 DNA punctuation Stem-loops structures terminators promoters attenuators

54 Termination of Transcription Genome Biology 2007,

55 http://www.youtube.com/watch?NR=1&feature=endscreen&v=cK-OGB1_ELE

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57 BioEssays 24:700–707, ß 2002 Wiley Periodicals, Inc.


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