Introduction to Bioinformatics and Computational Genomics

Week 7Gene content and pan-genomes

The E. coli result from week 1, done properly: cluster genes into families across strains, then split the result into core, shell and cloud.

Questions this week answers

  • How do you get from a pile of protein sequences to gene families?
  • You sequence a twentieth strain and find sixty new gene families. What does that tell you about the species?
  • Where in a pan-genome would you expect recently acquired genes to appear?

By the end of this week you can

  • Describe how an all-against-all BLAST becomes a set of gene families
  • Partition a gene presence-absence matrix into core, shell and cloud
  • Tell an open pan-genome from a closed one, and say what each implies
0 of 4 done

  1. Open or closed is a question about a curve

    Sequence more strains and watch the pan-genome grow. Then find the point where another strain stops being worth sequencing.

    With the exponent at 0.30 the sum never converges: strain 500 still brings 62 new genes. This is an open pan-genome, and it means the species is taking DNA from outside itself faster than sampling can catch up.

    Pan-genome4,0232,500 core + 1,523 accessory
    Next strain would add234still finding novelty
    Core share62%after 5 strains
    At 500 strainsstill climbing
    Each one is compared against everything sequenced before it.
    Heaps' law exponent. Above 1 the pan-genome converges; at or below 1 it does not.
    How much novelty a typical strain carries.
    Genes present in every strain. This is what makes it the species.
    Things to try0 of 3

    Core, shell and cloud vocabulary from the week 7 pan-genome lecture.

What should survive this week

  • All-against-all BLAST produces a similarity network; MCL clusters it; each cluster is a gene family. Roary is one implementation, not the method.
  • Core, shell and cloud. Core makes it this species, shell is lifestyle, cloud is recent and often the interesting part.
  • An open pan-genome keeps growing with every new strain, which means the species freely exchanges DNA with its environment.
  • Rhizobial symbiosis genes sit on plasmids and integrative conjugative elements, so they behave exactly like cloud genes should.