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Biology 301 Computational Biology Phylogenetic Trees Molecular Data and Applications Relevant Dutton

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Biology 301 - Computational Biology. Phylogenetic Trees ... Hasegawa: BF; SR (Ts Tv) Page 5.20: Think About. BF = base frequency, SR = substitution rate; ... – PowerPoint PPT presentation

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Title: Biology 301 Computational Biology Phylogenetic Trees Molecular Data and Applications Relevant Dutton


1
Biology 301 - Computational BiologyPhylogenetic
Trees - Molecular Data and ApplicationsRelevant
Dutton Lectures, Page Sections, BFD Ch. 9
(PJ)In advance for next time and final Sauter
paper (for Wednesday) and Golding paper (for
final).
2
  • Molecular Data Assumptions
  • Sequence information is correct/accurate
  • Homologous - sequences, aligned regions
  • Dataset - adequate representation
  • Dataset characters adequately variable
  • All sequences evolved via a single model
  • - all positions evolved independently
  • - substitution rates equal
  • - base composition is the same

3
  • The danger of generating incorrect results is
    inherently greater in computational phylogenetics
    than in many other fields of science.
  • Authors, Bioinformatics - A Practical Guide to
    the Analysis of Genes and Proteins

4
  • Review Duttons Stuff
  • Structure and Function of Phylogenetic Trees
  • Using legends to calculate genetic change
  • Will briefly discuss Distance, MP, and ML
  • BOOTSTRAP same
  • Testing of phylogenetics programs

5
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6
  • A Few Emphatics
  • Distance alignments converted to distance
  • Discrete aligned position data retained
  • - Parsimony low tree score wins
  • - Likelihood most probable based on model
  • BOTH can invoke substitution rates, weights
  • Read ML - we will not be doing in lab.

7
  • Distance Critiques
  • GOOD fast and cheap
  • BAD LOSS of aligned character data
  • BAD no way to apply weights to regions
  • BAD strong stochastic assumptions
  • In tests poor with similar sequences, slightly
    better with long branching less similar.

8
  • MP Critiques
  • GOOD moderately fast and cheap
  • BETTER less stochastic assumptions
  • YOUR CALL is life/evolution parsimonious?
  • In tests excellent to good with similar
    sequences, moderately poor with long branching
    less similar.

9
  • ML Critiques
  • BAD EXPENSIVE and slow
  • DIFFICULT all data must share same model
  • DIFFICULT how many models are there?
  • In tests top performer with similar and
    dissimilar data using one model.

10
  • Evolution Models
  • Carefully review Page 5.14
  • JC BF and SR (Ts Tv)
  • Kimura BF but ? SR (Ts ? Tv)
  • Felsenstein ? BF SR (Ts Tv)
  • Hasegawa ? BF ? SR (Ts ? Tv)
  • Page 5.20 Think About
  • BF base frequency, SR substitution rate
  • Ts transitions Tv transversions

11
  • Schools of Evolution
  • Trait-Based (pre-1960s)
  • Classical natural selection purified/stabilized
  • Balance natural selection drove diversity
  • Molecular-Based (post-1960s)
  • Neutralists more mutations neutral
  • Selectionists more mutations advantageous
  • Are non-adaptive traits parsimonious?

12
  • Agreeable Molecular Concepts
  • More functionally constrained, lower SR
  • Less constrained/non-coding, high SR
  • Third codon position, high SR
  • Different GC ratios - Why?
  • More G/C in early monomer pools
  • Hydrogen bond stability and hot earth
  • Associated with higher recombination
  • Shorter generation time in prokaryotes

13
Applications Beyond Organismal Phylogeny
  • Basic Identification
  • Typified by your 16S lab project
  • Yellowstone unknowns - you are solving
  • Compare with Noahs Ark dataset
  • Assess location to infer phylogeny
  • Nowadays, BLAST is acceptable for ID
  • Identification applications include research,
    epidemiology, and even forensics.

14
  • Assessing Horizontal/Lateral Gene Transfer
  • Acquiring new genes
  • MUST compare with known molecular clock
  • If topologies different assume acquired
  • BACTERIAL PROJECTS 16S gene clock
  • Compare your genes to 16S trees

15
  • Gene Duplication and Gene Family History
  • Typical for eukaryotic studies
  • Compare molecular clock species tree
  • With tree of all gene family members
  • Look For widely distributed species genes
  • DIFFICULT why I dont study eukaryotes!
  • None of you should encounter these in your
    projects so it is best to avoid making these
    calls.

16
  • Host-Parasite Co-Evolution
  • Page, Figure 8.10
  • Compares genes from host to clock
  • And genes from parasite to clock
  • AND host gene tree to parasite gene tree
  • Look For host and parasite ? either clock
  • AND LOOK FOR host parasite!
  • Hydrogenase - compare eukaryotic to prokaryotic
    to guess bacterial symbiont.

17
  • Addressing Time (and place)
  • Extinct organism DNA (on NCBI)
  • Calibration of trees to fossil record
  • Calibrating mutation rates controversial!!!!
  • Some less controversial applications
  • - when pathogens invaded given hosts
  • - origin of epidemics in time and place
  • Several projects may want to consider this.

18
  • Molecule or Drug Design
  • Class Brainstorm - More On Final
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