DOI: 10.5061/dryad.zgmsbccdn
title: Strong selective environments determine evolutionary outcome in time-dependent fitness seascapes

description: The impact of fitness landscape features on evolutionary outcomes has
 attracted considerable interest in recent decades. However, evolution
 often occurs under time-dependent selection in so-called fitness seascapes
 where the landscape is under flux. Fitness seascapes are an inherent
 feature of natural environments, where the landscape changes owing both to
 the intrinsic fitness consequences of previous adaptations and extrinsic
 changes in selected traits caused by new environments. The complexity of
 such seascapes may curb the predictability of evolution. However,
 empirical efforts to test this question utilising a comprehensive set of
 regimes are lacking. Here we employed an in vitro microbial model system
 to investigate differences in evolutionary outcomes between time-invariant
 and -dependent environments, including all possible temporal permutations,
 with three subinhibitory antimicrobials and a viral parasite (phage) as
 selective agents. Expectedly, time-invariant environments caused stronger
 directional selection for resistances compared to time-dependent
 environments. Intriguingly, however, multidrug resistance outcomes in both
 cases were largely driven by two strong selective agents (rifampicin and
 phage) out of four agents in total. These agents either caused
 cross-resistance or obscured the phenotypic effect of other resistance
 mutations, modulating the evolutionary outcome overall in time-invariant
 environments and as a function of exposure epoch in time-dependent
 environments. This suggests that identifying strong selective agents and
 their pleiotropic effects is critical for predicting evolution in fitness
 seascapes, with ramifications for evolutionarily informed strategies to
 mitigate drug resistance evolution. 
description: The dataset was collected from a 48-day serial passage experiment
 through phenotypic measurements at the population or clone level in the
 lab (curated_pheno_data.txt) or whole-genome sequencing to detect genomic
 mutations (curated_variants.txt) as specified in the manuscript, metadata,
 and detailed metadata descriptions below.
description: <strong>curated_variants.txt</strong>
 "id": unique sample ID (original well plate ID and
 location of clone as well as antibiotic treatment sequence
 information) "plate": 96-well plate ID (1-5
 without phage and 1P-5P with phage)
 "antibiotic_sequence": antibiotic treatment sequence
 using understandable abbreviations (no = no antibiotic; nal = nalidixic
 acid; rif = rifampicin; spe = spectinomycin; all = all antibiotics
 together throughout experiment)
 "strain_orig": original E. coli substrain annotation
 from sequencing metadata (R6 = 606; R7 = 607-like mutant)
 "strain_corrected": E. coli substrain information (R6 =
 606; R7 = 607-like mutant) corrected for erroneous annotation in
 sequencing metadata (this should be used for any analyses on E. coli
 substrain effect) "phage": presence of phage
 (0 = absent; 1 = present) "chrom": E. coli
 R606 reference genome accession (NC_012967)  
 "pos": nucleotide position on reference genom       
   "ref": reference allele 
 "alt": alternative (mutated) allele      
 "effect": predicted effect of mutated allele (e.g.
 synonymous_variant or frameshift_variant)         
 "effect_simplified": predicted effect of mutated allele
 simplified into three categories: synonymous, nonsynonymous and
 intergenic     "impact": predicted impact of
 mutated allele (LOW, MODERATE, or HIGH)       
 "gene": name of affected gene
 "gene_id": ID code of affected gene
 "na_change": nucleic acid change in affected
 gene "aa_change": amino acid change in
 affected gene     "genotype": whether given
 clone contains given mutation (0 = absence of mutation; 1 = presence of
 mutation)    "nal_res": whether given clone
 is phenotypically resistant to nalidixic acid (0 = susceptible; 1 =
 resistant)                       "rif_res":
 whether given clone is phenotypically resistant to rifampicin (0 =
 susceptible; 1 = resistant)                 
 "spe_res": whether given clone is phenotypically
 resistant to spectinomycin (0 = susceptible; 1 = resistant)               
      "phage_res": whether given clone is
 phenotypically resistant to bacteriophage (0 = susceptible; 1 =
 resistant)      Missing values and data to be removed
 prior to analyses are described in detail in the metadata described
 above.