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Evolution on empirical adaptive landscapes

Yoav Ram
April 06, 2017

Evolution on empirical adaptive landscapes

The increasing availability of empirical adaptive landscapes in microbes pro- vides an opportunity, for the rst time, to study evolutionary theory on real- istic adaptive landscapes. We demonstrate this new approach by simulating adaptive evolution of a haploid, asexual population on the A. nigeri and the E. coli TEM empirical landscapes. Our results demonstrate some interesting evolutionary phenomena. First, adaptation starts with a big leap forward, but additional tness increases become smaller and further apart. Second, in the smooth E. coli TEM landscape, every genotype along the evolutionary trajec- tory reached high frequency before the next genotype emerged and increased in frequency. In contrast, in the rugged A. niger landscape, only four genotypes reach a high frequency, although adaptation proceeds through seven di erent genotypes. These di erences have profound e ects on our ability to predict the trajectory and pace of adaptation. We consider this new approach critical for our understanding of many biological phenomena, from emergence of drug resistance to formation of microbial communities.

Yoav Ram

April 06, 2017
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  1. Empirical adaptive landscapes How to get them? • Evolutionary experiments

    • Phylogeny • Random mutagenesis de Visser & Krug, Nat Rev Gen 2014 Yoav Ram / ISM 2017 9
  2. Example 1: E. coli TEM • β-lactamase TEM gene in

    E. coli • 5 point mutations • Increase resistance to cefotaxime ~100,000-fold. Weinreich et al., Science 2006 Image: Wikipedia Yoav Ram / ISM 2017 10
  3. Example 2: Aspergillus niger The black mould Fungus • 5

    auxotrophic mutations • 2 resistance mutations • 1 spore color mutation. de Visser et al., Evolution 1997 Image: Wikipedia Yoav Ram / ISM 2017 12
  4. Example 3: tRNA gene • 65,000 yeast mutants in the

    gene • Fitness ~ biophysical properties of tRNA molecule • 1% single point mutations are beneficial • 42% are deleterious C. Li et al., Science 2016 Yoav Ram / ISM 2017 14
  5. Example 4: E. coli lac system • lac operator mutants

    • Measured expression and repression ability de Vos et al., PNAS 2015 Yoav Ram / ISM 2017 15
  6. Example 4: E. coli lac system • Adaptation facilitated by

    environmental changes • Population can escapes local peaks de Vos et al., PNAS 2015 Yoav Ram / ISM 2017 16
  7. Combining experiments & theory Simulations on empirical landscapes Experiments: -

    genotype ➡ fitness mapping Simulations: - test hypotheses - make predictions Yoav Ram / ISM 2017 17
  8. Comparison: A. niger vs. E. coli TEM Obolski, Ram &

    Hadany, 2017 Yoav Ram / ISM 2017 22
  9. Comparison: A. niger vs. E. coli TEM Obolski, Ram &

    Hadany, 2017 Yoav Ram / ISM 2017 23
  10. Applications in Microbiology • Generate testable predictions • Use predictions

    to intervene in evolution: • drug & pesticide resistance • virulence • conservation • Study open questions in evolution Yoav Ram / ISM 2017 24
  11. What's next? • Experimental side • More organisms, bigger landscapes,

    precise measurements • Estimates of mutation rates, population sizes, environmental changes • Theoretical side • New methods & models for communities, host-symbiont interactions... Yoav Ram / ISM 2017 25
  12. Thank you! • Collaborators: • Lilach Hadany, Tel-Aviv University •

    Uri Obolski, Univ. of Oxford • Preprint: Obolski, Ram & Hadany, bioRxiv 2017. doi: 10.1101/112177 • Source code: github.com/yoavram/ISM2017 • Homepage: www.yoavram.com • Funding: Yoav Ram / ISM 2017 26