An evolutionary model identifies the main evolutionary biases for the evolution of genome-replication profiles

  1. Rossana Droghetti
  2. Nicolas Agier
  3. Gilles Fischer
  4. Marco Gherardi
  5. Marco Cosentino Lagomarsino  Is a corresponding author
  1. Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, Italy
  2. Sorbonne Universitè, CNRS, Institut de Biologie Paris-Seine, Laboratory of Computational and Quantitative Biology, France
  3. Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, Milan, Italy and INFN sezione di Milano, Italy
  4. IFOM Foundation, FIRC Institute for Molecular Oncology, via Adamello 16, Italy
8 figures and 2 additional files

Figures

Figure 1 with 4 supplements
Experimental data motivate an evolutionary model for replication origins turnover.

(A) Distribution of the distance between neighbor origins in 10 Lachancea species, each histogram refers to a different species (data from Agier et al., 2018), and all the plots show a marked peak …

Figure 1—figure supplement 1
The phylogenetic tree of the 10 Lachancea yeasts clade.

Taken from [Agier et al., 2018], Figure 3A. L. kluyveri was used as the outgroup species. Hence, evolutionary events that occurred on both the L. kluyveri and the b2 branches (gray lines) could not …

Figure 1—figure supplement 2
The majority of new origins are born within a 20% distance from the midpoint of the associated interval.

The plot shows the empirical distribution of the fractional distance from the midpoints of nearby origins for newborn origins of the Lachancea clade. More than half of all the newborn origins are …

Figure 1—figure supplement 3
Experimental data on the evolutionary change of firing rates process.

(A) The firing rates Spearman correlation coefficient ρ between sets of corresponding origins decreases with increasing phylogenetic distance between species. Each point in the plot represents a …

Figure 1—figure supplement 4
The decaying trend of the Spearman correlation coefficient defines a characteristic time for the firing rate resample.

For each pair of species, we compute the Spearman correlation coefficient between the set of normalized firing rates belonging to corresponding origins. The figure shows the results of this …

The double-stall-aversion model reproduces origin turnover and distributions but fails to capture correlations between origin turnover and origin strength.

The plots show the simulations of the best-fitting double-stall-aversion model compared with empirical data. (A) Inter-origin distance distribution in simulated species (blue bars) compared to the …

Figure 3 with 1 supplement
A model where both fork stalling and interference affect fitness explain the correlations between origins of evolutionary events.

Result of the joint model best-fitting simulation compared with empirical data. (A) Inter-origin distance distribution in simulated species (blue bars) vs. empirical distribution for the 10 Lachancea

Figure 3—figure supplement 1
Linear chromosomes do not alter significantly the model outcomes.

We simulated eight linear chromosomes (the number of chromosomes of the majority of Lachancea species), with length equal to one eighth of the average genome size. We have modified the model so that …

Figure 4 with 2 supplements
Comparison of model predictions for the correlations of origin birth-death events.

The plots in the red upper box compare efficiency distributions of the best-fitting simulation of the two different models (bottom and central panels) with experimental data (top panel). Comparison …

Figure 4—figure supplement 1
The efficiency mechanism is necessary to reproduce the correlation between firing rates and evolutionary events.

Comparison between the firing rates events correlation for experimental data, double-stall-aversion model, and joint model. Only the joint model can reproduce this correlation, which is observed in …

Figure 4—figure supplement 2
Analytical predictions for the inter-origins distance distribution falsify the scenario whereby interference alone drives replication program evolution.

The plot shows a comparison between the empirical inter-origin distance distribution (red line, diamonds) and the analytical prediction from the scenario of origin birth-death driven by interference …

Figure 5 with 2 supplements
The efficiency/double-stall-aversion model predicts origin divergence.

The plots compare predictions of the evolutionary model on the extent of origin divergence (simulations of the Lachancea phylogenetic tree) with empirical data. (A) Box plot of origins efficiency …

Figure 5—figure supplement 1
The joint efficiency/double-stall-aversion model simulated on a cladogenetic structure reproduces all the results found for a single lineage.

The results refer to 100 different runs of the simulation of the joint model on the empirical tree structure compared with empirical data. (A) Inter-origin distance distribution in simulated species …

Figure 5—figure supplement 2
Simulations and empirical data show a similar variability in number of death and birth events across branches of the tree.

In each plot, a symbol corresponds to one branch of the phylogenetic tree, empty squares represent the simulations of the cladogenetic structure (100 different runs), and round black circles the …

Author response image 1
Subtree chosen for the model fit.
Author response image 2
The "uniform draw" model does not reproduce the inter origin distance distribution.

The figure compares the empirical distance distribution (red point line) with the one resulting from the simulation of the uniform draw model (blue bars) with γ=10. We choose this value because for …

Author response image 3
Newborn origins and conserved ones have similar distributions of firing rates.

The plot shows the probability distribution functions for the normalized firing rates for all the origins in the ten Lachancea species (red diamonds) and for those origins which have been gained in …

Additional files

Supplementary file 1

Results of the simplified log-likelihood tests of the joint and the double-stall-aversion model with the associated p-values.

Positive log-likelihood differences favor the joint model (see Materials and methods).

https://cdn.elifesciences.org/articles/63542/elife-63542-supp1-v2.txt
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https://cdn.elifesciences.org/articles/63542/elife-63542-transrepform1-v2.pdf

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