Figure 1.
Virtual Cell simulation protocol.
A schematic overview of the Virtual Cell model shows how resource can diffuse and be transported into the cell, where it is converted to energy molecule
and further catabolized into an unspecified end product. The expression of genes coding for different variants (differently evolved parameters for substrate affinities and binding motifs) of enzymes, pumps and TFs are differentially regulated depending on TF regulatory interactions with their promoters. Genes are located on a spatially explicit, circular genome. For our simulation protocol 100 populations consisting of 1024 cells each were randomly initialized and evolved under standard environmental conditions. From populations that reached high fitness (arbitrarily defined as a fitness higher than 0.85) 10 were selected for further environmental change testing. 1000 generations upon reaching high fitness these 10 selected populations were each subjected to 80 novel environmental conditions. From the 800 simulations fit runs were grouped into lineages with WGD and lineages without WGD within their line of descent. A neutral control set was formed by continuing evolution of the initially fit lineages under identical standard environmental conditions.
Figure 2.
Fitness and whole genome duplication results.
(A,B) Simulations binned on the time of reaching high fitness (0.85), when adapting for the first time to standard conditions (A) and re-adapting after an environmental change (B). The bars are split into a fraction that adapted with (red) and without (cyan) a WGD. The inset of B shows the differently shaped distributions of adaptation times on a log-scale for WGD and non-WGD lineages, with WGD lineages showing a sharper peak at intermediate adaptation times. (C) Fractions of runs that became fit after environmental change, separated for runs with and without an ancestral WGD respectively. D,E and F show fitness evolution of three example simulations, where the initial adaption (gray background) is the same and subsequent re-adaptation occurs in different environments (yellow background). We show an example of re-adaptation with additional rounds of WGD at an intermediate time scale (D) and re-adaptation without WGD (E,F) on a longer timescale (E) and on very short timescale of a few tens of generations, after a sharp fitness drop (F).
Figure 3.
Fraction of conserved ancestral gene content through evolutionary time.
The gene content of ancestors at the time of environmental switch was used as reference. At 1000 generation intervals, the overlap in gene content of descendants with the reference was measured. All genes inherited one to one from the ancestral reference (not counting copies from subsequent duplication events) count towards the retained fraction of the total ancestral gene content, in WGD lineages (red), non-WGD lineages (blue) and a neutral control set where the environment was kept the same (gray). Boxes and whiskers show the 50% (box) and 75% (whiskers) ranges of the data around the median (line). Triangles and the upper edge of the shaded area show the averages of the environmental change and neutral evolutionary runs, respectively. The inset shows the distribution of genome sizes.
Figure 4.
Deletion and point mutation rates in the line of descent.
(A) Rate of genes deleted per accepted deletion event as a fraction of total genome size. These fractions were averaged for all fit runs with (red) and without (cyan) a WGD as well as a control set of runs that continued without environmental change (gray), and binned in 1000 generation intervals. In the inset, accepted deletion fractions are per generation instead of per event. (B) Accepted point mutation rates per generation as a fraction of total genome size. The fractions were averaged for all fit runs with (red) and without (cyan) a WGD as well as a control set of runs that continued without environmental change (gray), and binned in 1000 generation intervals.
Figure 5.
Intact ohnologs as a fraction of conserved WGD content.
Of the conserved gene content from the ancestral reference genome the fraction of genes in complete WGD pairs (ohnologs) was plotted, per gene category. Solid lines show the intact ohnologs in the evolutionary data, while dashed lines represent the ohnolog fractions obtained when the same number of deletions per category were applied randomly and in the absence of selection. Shaded areas highlight the difference between evolutionary and neutral simulation results.
Figure 6.
Ancestral outdegree and binding site conservation of conserved TFs.
At the time of WGD all TFs were identified and their outdegree and binding site motifs recorded. At 1000 generation intervals conserved TFs from the time of WGD or, if there was no WGD, from the time point when environmental change was applied for the re-adaptation experiments, were identified in the genomes in the line of descent. (A) The average ancestral outdegree of the retained TFs (recorded at the reference time point) was divided by the average outdegree of the all ancestral TFs, thus providing a measure of the influence of ancestral connectivity on the rate of conservation of TFs. For WGD lineages this relative outdegree of conserved TFs was measured separately for ohnologs (red) and singles (yellow). For comparison, the analysis was also done for non-WGD (cyan) lineages and a neutrally evolving control set (gray). (B) The current and ancestral binding sequences of the TFs were compared and conservation score set to 1 if they remained the same and 0 otherwise and all scores averaged per individual.