Fig 1.
Overview of the study and the model.
(a) Study flow diagram. Red color indicates blocks/functions simulated in this study. Dashed blocks specify measurements. Variables correspond to mRNA levels () and various measurements (
). See the main text for details. (b) Topology of the computational model used in this study, which includes m mRNAs and a shared free pool of ribosomes. Gi(z) denotes the initiation rate to mRNA i, and Ri(t) denotes the translation rate of mRNA i at time t. (c) An example of the free ribosomal pool (top), the GFP translation rate (middle) and the GFP mean ribosomal density (bottom) as a function of t ∈ [0, 192] for a periodically varying GFP mRNA levels with period T = 16.
Table 1.
Computational model parameters.
Fig 2.
The effect of endogenous gene mRNA levels.
(a) za, , and
as a function of the number of oscillating genes chosen incrementally from a mRNA levels-sorted list of genes (see details in the Materials and methods section), (dashed-line), and genes chosen randomly from the gene list (solid-line), for A = 1/2. Note that the results for za and
when oscillating a typical gene set are very similar (the solid-line for za cannot be distinguished from the solid-line
) (b) The corresponding variances. (c) za,
, and
as a function of the normalized amplitude A ∈ [0.1, 0.9] when oscillating the cell cycle related genes. (d) The corresponding variances.
Fig 3.
The effect of heterologous gene mRNA levels and initiation rates.
(a) as a function of
and different values of α, for A = 1/2, T = 16, and
. (b)
as a function of
and different values of α, for A = 1/2, T = 16, and
. (c)
as a function of A for α = 0.8,
, T = 16, and
. (d)
as a function of A for α = 0.8,
, T = 16, and
.
Table 2.
Mutated GFP genes translation properties.
Fig 4.
The effect of heterologous gene mRNA levels and elongation rates.
(a) Block diagram of the current test. (b) Normalized za as a function of , α = 0.8 and α = 3.2 for A = 1/2, T = 16, and
. “ORG” denotes the original (non-mutated) GFP. (c) Legend of the sub-figures. The up-to-down order corresponds to the performance ranking, per
value, in sub-figures (b), (d), and (e), i.e. HIGH results in the largest measurement values, followed by ORG, etc. (d) Normalized
(upper figure) and normalized
(lower figure) as a function of
, α = 0.8 and α = 3.2 for A = 1/2, T = 16, and
. (e) Normalized
(upper figure) and normalized
(lower figure) as a function of
, α = 0.8 and α = 3.2 for A = 1/2, T = 16, and
.
Fig 5.
The effect of the average ribosomal pool.
(a) Block diagram of the current test. (b) Normalized za as a function of of GFP_HIGH_RD, for α = 0.8, A = 1/2, T = 16, and different values of
. (c) Legend of the sub-figures. The right-to-left order corresponds to the performance ranking, per
value, in sub-figures (b), (d), and (e), i.e.
results in the largest measurement values, followed by
, etc. (d) Normalized
(upper figure) and normalized
(lower figure) as a function of
of GFP_HIGH_RD, for α = 0.8, A = 1/2, T = 16, and different values of
. (e) Normalized
(upper figure) and normalized
(lower figure) as a function of
of GFP_HIGH_RD, for α = 0.8, A = 1/2, T = 16, and different values of
.
Table 3.
Statistics as a function of the average free pool at steady-state for A = 0.35, T = 16, α = 0.8, and .
Table 4.
The 30 (out of 800) cell cycle related genes reported in [17] that we lack mRNA measurements for (and thus are not used in our simulations).
Fig 6.
The RFM as a chain of n sites of codons.
Each site is described by a state variable xi(t) ∈ [0, 1], expressing the normalized ribosome occupancy at site i at time t. λ0 is the initiation rate, and λi is the elongation rate from site i to site i + 1. Translation rate at time t is R(t) ≔ λnxn(t).