A unified framework for measuring selection on cellular lineages and traits

  1. Shunpei Yamauchi
  2. Takashi Nozoe
  3. Reiko Okura
  4. Edo Kussell
  5. Yuichi Wakamoto  Is a corresponding author
  1. Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Japan
  2. Department of Biology, New York University, United States
  3. Department of Physics, New York University, United States
  4. Research Center for Complex Systems Biology, The University of Tokyo, Japan
  5. Universal Biology Institute, The University of Tokyo, Japan
8 figures, 4 tables and 1 additional file

Figures

Representative single-cell lineage trees.

(A) Time-lapse images of a growing microcolony of Escherichia coli expressing green fluorescent protein (GFP) from plasmids. Scale bars, 5 μm. (B) Cellular lineage trees for the microcolony in A. …

Conceptual illustration of the relationships between fitness landscapes, trait distributions, and selection strength.

(A) Non-uniform fitness landscape and broad trait distribution. The gray distribution represents a chronological distribution of lineage trait x; the cyan distribution represents a retrospective …

Relationships among chronological distributions’ shape and selection strength measures.

(A) Graphical representation of various fitness and selection strength measures by KX(ξ)-plot. Blue curve represents KX(ξ). The area between the horizontal axis and KX(ξ) in the interval 0ξ1 outlined in red …

Figure 4 with 1 supplement
Population growth rate response to cell removal perturbation.

(A) Scheme of random cell removal. Here, we consider the situation where cells were removed probabilistically after each cell division. Red crosses represent cell removal positions in the tree. The …

Figure 4—figure supplement 1
Response of population growth rate to cell removal perturbation with positive mother-daughter correlations of generation time.

We conducted the simulations of cell population growth with positive mother-daughter correlations (Gray points). We considered the generation time distribution that follows a gamma distribution with …

Figure 5 with 2 supplements
Application of cell lineage statistics to experimental data.

(A) Contributions of the cumulants of a fitness landscape to population growth. W1(D) and W2(D) were evaluated for the experimental cell lineage data from E. coli (red), M. smegmatis (blue), S. pombe

Figure 5—figure supplement 1
Chronological distributions of division count, Qcl(D).

(A-G) E. coli. (H). M. smegmatis. (I-O) S. pombe. P. L1210 mouse leukemia cells.

Figure 5—figure supplement 2
Graphical representation of KD(ξ).

A-G. E. coli. H. M. smegmatis. I-O. S. pombe. P. L1210 mouse leukemia cells.

Strong selection in the E.coli population regrowing from a late stationary phase.

(A) Time-lapse images. Cellular regrowing dynamics from early and late stationary phases were observed by time-lapse microscopy. Cells were enclosed in the microchambers etched on coverslips. The …

Figure 7 with 1 supplement
Fitness landscapes and selection strength for RpoS expression levels.

(A) Fitness landscapes for the time-averaged concentration (mean fluorescent intensity) for RpoS-mCherry. The time-averaged mean fluorescent intensity of RpoS-mCherry was adoped as a lineage trait X

Figure 7—figure supplement 1
The relative selection strength values for time-averaged RpoS-mCherry and GFP fluorescence intensity compared with the randomized data.

The blue histograms show the distributions of the relative selection strength values calculated from the lineage data in which the correspondences between division counts and trait values are …

Appendix 1—figure 1
Analytical calculations of KD(ξ) and related relations given specific form of division count distributions.

(A) Chronological division count distributions. ϕ=0.3 and ϕ=ϕ0(=0.5857) are binomial, ϕ=1 is Poisson and ϕ=1.6 is negative binomial. D¯=20(1-ϕ0) is fixed. (B) Cumulative contributions of fitness cumulants. Parameter values …

Tables

Table 1
Relationships between KX(ξ) and quantities in cellular lineage statistics.
Quantities in lineage statisticsSymbolCorrespondence to KX(ξ)
FitnessPopulation growthτΛKX(1)
Chronological mean fitnessh(X)clKX(0)
Retrospective mean fitnessh(X)rsKX(1)
Chronological fitness varianceVar[h(X)]clKX′′(0)
Retrospective fitness varianceVar[h(X)]rsKX′′(1)
Selection strengthJeffreys divergence bet. Qcl(X)
and Qrs(X)
SJF[X]KX(1)-KX(0)
KL divergence of Qcl(X) from 
Qrs(X)
SKL(1)[X]KX(1)-KX(0)
KL divergence of Qrs(X) from 
Qcl(X)
SKL(2)[X]KX(1)-KX(1)
Growth rate gain/lossGrowth rate gainSKL(1)[D]/τΛ1-KD(0)/KD(1)
Additional growth rate loss upon perturbation-SKL(2)[D]/τΛ1-KD(1)/KD(1)
Table 2
Summary of cellular species, culture conditions, and observation setup used in the experiments in Figure 5.
SpeciesLabelStrainMediumTemperature (°C)Device
E. colirpoS-mcherry glucose_30°CMG1655 F3 rpoS-mcherry /pUA66-PrpsL-gfpM9 minimal medium +0.2%(w/v) glucose +1/2 MEM amino acids solution (Sigma)30Microchamber arrayThis study
E. colirpoS-mcherry glucose_37°CMG1655 F3 rpoS-mcherry /pUA66-PrpsL-gfpM9 minimal medium +0.2%(w/v) glucose +1/2 MEM amino acids solution (Sigma)37Microchamber arrayThis study
E. colirpoS-mcherry glycerol_37°CMG1655 F3 rpoS-mcherry /pUA66-PrpsL-gfpM9 minimal medium +0.1%(v/v) glycerol +1/2 MEM amino acids solution (Sigma)37Microchamber arrayThis study
E. colif3nw -smF3NWM9 minimal medium +0.2%(w/v) glucose +1/2 MEM amino acids solution (Sigma)+0.1mM Isopropyl β-D-1 thiogalactopyranoside (IPTG)37Agar padNozoe et al., 2017
E. colif3nw +smF3NWM9 minimal medium +0.2%(w/v) glucose +1/2 MEM amino acids solution (Sigma)+0.1 mM Isopropylβ-D-1 thiogalactopyranoside (IPTG)+100
μg/ml streptomycin
37Agar padNozoe et al., 2017
E. colif3ptn001 -smF3/pTN001M9 minimal medium +0.2%(w/v) glucose +1/2 MEM amino acids solution (Sigma)+0.1 mM Isopropylβ-D-1 thiogalactopyranoside (IPTG)37Agar padNozoe et al., 2017
E. colif3ptn001+smF3/pTN001M9 minimal medium +0.2%(w/v) glucose +1/2 MEM amino acids solution (Sigma)+0.1 mM Isopropylβ-D-1 thiogalactopyranoside (IPTG)+200
μg/ml streptomycin
37Agar padNozoe et al., 2017
M. smegmatismc2155 7H9mc2155Middlebrook 7H9 medium +0.5% albumin +0.2% glucose +0.085% NaCl+0.5% glycerol +0.05% Tween-8037Membrane coverWakamoto et al., 2013
S. pombeEMM28HN0025Edinburgh minimal medium +2% (w/v) glucose28Mother machineNakaoka and Wakamoto, 2017
S. pombeEMM30HN0025Edinburgh minimal medium +2%(w/v) glucose30Mother machineNakaoka and Wakamoto, 2017
S. pombeEMM32HN0025Edinburgh minimal medium +2%(w/v) glucose32Mother machineNakaoka and Wakamoto, 2017
S. pombeEMM34HN0025Edinburgh minimal medium +2%(w/v) glucose34Mother machineNakaoka and Wakamoto, 2017
S. pombeYE28HN0025Yeast extract medium +3%(w/v) glucose28Mother machineNakaoka and Wakamoto, 2017
S. pombeYE30HN0025Yeast extract medium +3%(w/v) glucose30Mother machineNakaoka and Wakamoto, 2017
S. pombeYE34HN0025Yeast extract medium +3%(w/v) glucose34Mother machineNakaoka and Wakamoto, 2017
L1210 mouse leukemia cellL1210 RPMI-1640L1210 (ATCC CCL-219)RPMI-1640 medium (Wako)+10% fetal bovine serum (Biosera) under 5% CO2 atmosphere37Mother machineSeita et al., 2021
Table 3
Summary of the data used in the analysis in Figure 5.

tstart and tend are the start and end times for the analysis time window τ.

Specieslabelτ(hr)tstart(hr)tend(hr)N0Nτ
E. colirpoS-mcherry glucose_37°C50.955.951633989
E. colirpoS-mcherry glucose_30°C80.958.951976173
E. colirpoS-mcherry glycerol_37°C6.50.957.452535825
E. colif3nw-sm5053054343
E. colif3nw +sm5052913164
E. colif3ptn001-sm5059849229
E. colif3ptn001+sm5059777429
M. smegmatismc2155 7H9101.7511.7539311
S. pombeEMM2816701671148-
S. pombeEMM301310131963-
S. pombeEMM32123.50123.5883-
S. pombeEMM3415201521078-
S. pombeYE2810801081177-
S. pombeYE3090090866-
S. pombeYE3478078863-
L1210 mouse leukemia cellL1210 RPMI-164060060474-
Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Recombinant DNA reagentpUA66-PrpsL-gfp (plasmid)Zaslaver et al., 2006
Strain, strain background (Escherichia coli)MG1655 F3Wakamoto labMG1655ΔfliCΔfimAΔflu
Strain, strain background (Escherichia coli)MG1655 F3 rpoS-
mcherry /pUA66-P rplS-gfp
Wakamoto labMG1655ΔfliCΔfimAΔflu rpoS-mcherry /pUA66-PrplS-gfp

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