Microbial evolution and the spread of infectious disease

Richard Neher
Biozentrum, University of Basel

slides at neherlab.org/201812_CBB_Seminar.html

Human Influenza A viruses

slide by Trevor Bedford

Weekly numbers of positive influenza tests in the US by subtype

Data by the US CDC

  • Influenza virus evolves to avoid human immunity
  • Vaccines need frequent updates

Clonal interference and traveling waves

RN, Annual Reviews, 2013; Desai & Fisher; Brunet & Derrida; Kessler & Levine

Typical tree

Bolthausen-Sznitman Coalescent

RN, Hallatschek, PNAS, 2013; see also Brunet and Derrida, PRE, 2007

Bursts in a tree ↔ high fitness genotypes

Can we read fitness of a tree?

Predicting evolution

Given the branching pattern:

  • can we predict fitness?
  • pick the closest relative of the future?
RN, Russell, Shraiman, eLife, 2014

Fitness inference from trees

$$P(\mathbf{x}|T) = \frac{1}{Z(T)} p_0(x_0) \prod_{i=0}^{n_{int}} g(x_{i_1}, t_{i_1}| x_i, t_i)g(x_{i_2}, t_{i_2}| x_i, t_i)$$
RN, Russell, Shraiman, eLife, 2014

Prediction of the dominating H3N2 influenza strain

  • no influenza specific input
  • how can the model be improved? (see model by Luksza & Laessig)
  • what other context might this apply?
RN, Russell, Shraiman, eLife, 2014


joint work with Trevor Bedford & his lab

HIV-1 evolution within one individual

silouhette: clipartfest.com, Zanini at al, 2015. Collaboration with Jan Albert and his group

Population sequencing to track all mutations above 1%

Zanini et al, eLife, 2015

Bacterial evolution

  • every genome contains a different set of genes
  • horizontal transfer
  • genome rearrangements
  • variable divergence along the genome
  • important parts sit on plasmids,
    flanked by repetitive sequence
  • short read assemblies tend to be fragmented
  • annotations of variable quality
panX by Wei Ding
  • pan-genome identification pipeline
  • phylogenetic analysis of each orthologous cluster
  • detect associations with phenotypes
  • fast: analyze hundreds of genomes in a few hours
  • github.com/neherlab/pan-genome-analysis
Ding, Baumdicker, RN, 2017

HIV acknowledgments

  • Fabio Zanini
  • Jan Albert
  • Johanna Brodin
  • Christa Lanz
  • Göran Bratt
  • Lina Thebo
  • Vadim Puller

Influenza and Theory acknowledgments

  • Boris Shraiman
  • Colin Russell
  • Trevor Bedford
  • Oskar Hallatschek


  • Trevor Bedford
  • Colin Megill
  • Pavel Sagulenko
  • Sidney Bell
  • James Hadfield
  • Wei Ding
  • Emma Hodcroft
  • Sanda Dejanic