Phylogeny and Comparative Genomics

Supporting material for MMG 801 Lectures on 'Phylogeny and Comparative Genomics.'
[PDF slides not accessible enough? Please reach out to me]

Learning Objectives

• Phylogeny & Construction of Phylogenetic Trees (species and gene)
• Comparative Genomics & Pangenomes
• In class hands-on demo for two most useful tools:
  • BLAST for similarity searches, MSA (multiple sequence alignment) and phylogenetic trees
  • PATRIC for Microbial genomics (esp. as a database)
  • For this, please explore the web-versions for the 'how' + papers to orient you on the 'why' & 'what'
  • Example input files in the data folder: fasta + saved BLAST search strategy.
  • We will address your Qs + use these with the web-tools in class on Thursday!

Outline

Lectures 1 & 2 | Phylogenetics

2020: slides | video | HW

2021: slides | HW

PDF, video, homework assignment are all accessible w/ your MSU ID Google login.

• Intro to phylogeny
  • Evolution of desserts
  • Activity: Pizza tree
  • Phylogeny and Phylogenetic trees
    • Carl Woese and the three domains of life
    • Bacterial evolution
    • Species trees vs gene trees
      • Homologs, Orthologs, Paralogs
      • Tangled tree
  • Methods to build phylogenetic trees
    • Distance-based methods | UPGMA, Neighbor-joining
    • Character-based methods | Max. parismony, Max. Likelihood, Bootstrap confidence estimation
    • Strengths and Weaknesses of each approach
    • Qn: Which alignment is better?
  • Sequence evolution & sequence alignment
    • The amazing Margaret Dayhoff
    • BLOCKS db and BLOSUM substition matrix
    • Activity: How do you cluster these? Distance -> Clusters -> Trees
    • Qn: Vertical distance in hierarchical rooted trees
  • Gene trees & sequence alignment (w/ BLAST)
    • NCBI Protein
    • NCBI BLAST
    • Protein of interest -> [Accession Number -> Fasta sequence] -> BLAST for homologs
    • Demonstration of paralogs vs orthologs w/ Ravi 2018 actinobacterial PspA tree
  • Tools to explore
    • iTol: Interactive Tree of Life
    • TimeTree
    • NextStrain for CoV, Ebola, Dengue, Mtb and more!
    • For similarity searches: BLAST (BLASTp, DELTA-BLAST)
    • For multiple sequence alignment: MUSCLE, T-Coffee, Jalview
    • For tree building: FigTree, FastTree
    • For phylgoenetic trees using distance-based and character-based methods: BEAST, MEGA
  • Suggested reading:
    • Review on Phylogenetic Methods | a good overview of the phylogenetic tree-building techniques | Molecular phylogenetics: principles and practice. Yang Z, Rannala B. Nat Rev Genet. 2012;13(5):303-314.
    • BLAST Original paper | harder to read | Basic local alignment search tool. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. J Mol Biol. 1990 Oct 5;215(3):403-10.
    • BLAST | easier to read paper | Steps Used by the BLAST Algorithm. Mount DW. CSH Protoc. 2007 Jul 1;2007:pdb.ip41. doi: 10.1101/pdb.ip41.
    • Wiki: BLAST (biotechnology)
    • The book, Tangled Tree by David Quammen

Lecture 3 | Comparative genomics and pangenomes

2020: slides | HW

2021: slides | HW

• Species trees
• Genome sequencing
• Genome assembly
• Whole genome alignment
• Comparative genomics
• Pangenomes
• PATRIC

Questions?

• Email
• MSU Microsoft Teams (direct message to: Janani Ravi)
• 2020 Office hours (202009) at 4p on Friday (Sep 11) and Tuesday (Sep 16)
• 2021 Office hours: Friday 1–2p; Monday 10–11a