Recent progress in understanding evolutionary dynamics

Richard Neher
Biozentrum, University of Basel

slides at

Ernst Haeckel, 1879

From qualitative to quantitative

  • What are the relevant parameters?
  • How does adaptation and diversity depend on parameters?
  • How repeatable is evolution?
  • How predictable is evolution?
  • How gradual is evolution?

Population genetics & evolutionary dynamics

evolutionary processes ↔ trees ↔ genetic diversity

Concepts and typical assumptions -- 20th century

  • The world doesn't change!
  • Mutations happen one at a time!
  • Typical events dominate!

Fitness landscapes

Diffusion theory (Kimura)

$\frac{\partial P(x,t)}{\partial t} = \frac{\partial}{\partial x}\left[-sx(1-x)+\frac{\partial}{\partial x}\frac{x(1-x)}{N}\right]P(x,t)$
  • Stochastic dynamics of a single locus
  • Difficult to generalize to many loci

Coalescence theory (Kingman)

  • Backwards in time model
  • Predictions for diversity at many loci
  • Difficult to generalize to non-neutral variation

Development of sequencing technologies

We can now sequence...
  • thousands of bacterial isolates
  • thousands of single cells
  • populations of viruses, bacteria or flies
  • diverse ecosystems

Experimental evolution -- Lenski experiment

Rich Lenski, Ben Good, Michael Desai et al

Influenza A/H3N2

  • Influenza viruses evolve to avoid human immunity
  • Vaccines need frequent updates

Rapidly evolving RNA viruses -- HIV

  • Many adaptive mutations → mutation supply not limiting
  • Many competing clones → complex dynamics
  • Environments are constantly changing
silouhette:, Richman et al, 2003.

Clonal interference and traveling waves

Gerrish & Lenksi; Desai & Fisher; Kessler & Levine

Traveling wave models of adaptation

  • Speed of adaptation is logarithmic in population size
  • Environment (fitness landscape), not mutation supply, determines adaptation
  • Different models have universal emerging properties
  • Dispersal matters: well mixed populations different from dynamics in one or two dimensions
Desai & Fisher, Genetics

Bolthausen-Sznitman Coalescent

$T_c \sim \log N \quad\mathrm{instead\, of}\quad \sim N$
$\mathrm{rare\,jackpot\,events\,}P(n) \sim n^{-2}$
Brunet and Derrida, PRE, 2007; RN, Hallatschek, PNAS, 2013; Desai, Walczak, Fisher, Genetics, 2013

Testable predictions -- site frequency spectra

Kosheleva & Desai, Genetics, 2014; RN, Hallatschek, PNAS, 2013

Site frequency spectra observed in HIV populations

Zanini et al, eLife, 2015

Repeatability -- selecting 100 E. coli lines to live at 42C by Tenaillon et al

Extensive parallelism at the level of genes and pathways
Alternative adaptive path to heat adaptation
  • Drug resistance: repeated evolution of the same mutations is typical
  • Less well defined selection targets: repeatability is restricted to genes or pathways
  • Selection on quantitative traits: standing diversity determines response
  • Little success in a priori prediction of adaptive pathways

Predicting future populations

General idea

  • Future populations descend from present day high fitness individuals
  • Identify current high fitness individuals

Predicting influenza

  • Approach 1: leverage our understanding of trees of adapting populations
    (RN, Russell, Shraiman)
  • Approach 2: exploit historical patterns indicative of recent adaptation
    (Luksza and Lässig)
  • These methods now inform the WHO vaccine strain selection process.

Conclusions, limitations, questions

  • Good understanding of adapting populations under directional selection
  • Sequencing is easy, structure and function are hard
  • Limited ability to predict the nature of adaptations
  • Experimental evolution = artificial environments
    → atypical adaptation, dominated by loss of function mutations.
    Is this representative? Better/other systems?
  • Observable pathogen evolution → Coevolution.
    Is this a more general setting (or limited RNA to viruses)?
    Beyond one pathogen/one host?
  • Ecology gets in the way → coevolution, niche construction, variable environments
    How does adaptation interact with ecology and intra-species partitioning?
    Can we ever separate the environment from adaptation?
  • How does short term adaptation extrapolate to processes on longer time scales?