Electron micrographs of a cluster of minimal cells magnified 15,000 times.
Credit: Tom Deerinck and Mark Ellisman
University of California at San Diego.
University of California at San Diego.
It's turning out to be another terrible week for those few creationists capable, and willing, to read the science.
Here for example is a report on the work of a team led by evolutionary biologist, Professor Jay T. Lennon, of the Department of Biology in the College of Arts and Sciences at Indiana University. It shows a number of things that refute basic creationist dogmas:
- The team use a genetically engineered, stripped down version of the bacterium Mycoplasma mycoides, a parasitic organism that, in common with many parasites had lost genes in the course of its evolution as a dependent parasite in the gut of goats and similar animals, reducing its genome to just 901 genes. So here we have evolution by loss of information (something creationists claim can't happen because their dogma says loss of information is invariably detrimental) as the starting point of this research.
- The team then removed all but the essential genes needed to maintain a functional, reproducing cell, removing a further 45 percent of the genes, reducing the genome to just 493 genes, showing the massive amount of redundancy in a cell's genome - something that no intelligent designer would have designed, showing there was no intelligence in the design of M. mycoides. By comparison, a typical cell can contain 20,000 genes!
- The team then allowed the minimal cell to evolve for 300 days, or 2000 generations (equivalent to 40,000 years of human evolution). They found that even with a minimal genome and so fewer targets for mutation and selection to act on, the minimum cells evolved towards greater fitness, just as the TOE predicts.
- And of course, as with all biological research, there is the complete dependence on the TOE to understand and explain the results, with no hint of doubt in it's explanatory powers or any suggestion that the creationists superstition with its magic and unproven supernatural entity might offer a better explanation of the facts.
The research groups findinga are published, open access in Nature:Artificial cells demonstrate that “life finds a way”
You won't find any Velociraptors lurking around evolutionary biologist Jay T. Lennon's lab; however, Lennon, a professor in the College of Arts and Sciences Department of Biology at Indiana University Bloomington, and his colleagues have found that life does indeed find a way. Lennon's research team has been studying a synthetically constructed minimal cell that has been stripped of all but its essential genes. The team found that the streamlined cell can evolve just as fast as a normal cell—demonstrating the capacity for organisms to adapt, even with an unnatural genome that would seemingly provide little flexibility.Listen, if there's one thing the history of evolution has taught us is that life will not be contained. Life breaks free. It expands to new territories, and it crashes through barriers painfully, maybe even dangerously, but . . . life finds a way
Ian Malcolm, Jeff Goldblum's character in Jurassic Park
1993 science fiction film.
For their study, Lennon’s team used the synthetic organism, Mycoplasma mycoides JCVI-syn3B—a minimized version of the bacterium M. mycoides commonly found in the guts of goats and similar animals.It appears there’s something about life that’s really robust. We can simplify it down to just the bare essentials, but that doesn’t stop evolution from going to work.
Professor Jay T. Lennon, corresponding author
Department of Biology
Indiana University, Bloomington, IN, USA
Over millennia, the parasitic bacterium has naturally lost many of its genes as it evolved to depend on its host for nutrition. Researchers at the J. Craig Venter Institute in California took this one step further. In 2016, they eliminated 45 percent of the 901 genes from the natural M. mycoides genome—reducing it to the smallest set of genes required for autonomous cellular life. At 493 genes, the minimal genome of M. mycoides JCVI-syn3B is the smallest of any known free-living organism. In comparison, many animal and plant genomes contain more than 20,000 genes.In principle, the simplest organism would have no functional redundancies and possess only the minimum number of genes essential for life. Any mutation in such an organism could lethally disrupt one or more cellular functions, placing constraints on evolution. Organisms with streamlined genomes have fewer targets upon which positive selection can act, thus limiting opportunities for adaptation.
Electron micrograph of a cluster of minimal cells magnified 15,000 times.The synthetically streamlined bacterium, Mycoplasma mycoides, contains less than 500 genes.Credit: Tom Deerinck and Mark Ellisman
National Center for Imaging and Microscopy Research
University of California at San Diego, CA, USA.
Although M. mycoides JCVI-syn3B could grow and divide in laboratory conditions, Lennon and colleagues wanted to know how a minimal cell would respond to the forces of evolution over time, particularly given the limited raw materials upon which natural selection could operate as well as the uncharacterized input of new mutations.
The researchers established that M. mycoides JCVI-syn3B, in fact, has an exceptionally high mutation rate. They then grew it in the lab where it was allowed to evolve freely for 300 days, equivalent to 2000 bacterial generations or about 40,000 years of human evolution.Every single gene in its [M. mycoides JCVI-syn3B] genome is essential. One could hypothesize that there is no wiggle room for mutations, which could constrain its potential to evolve.
Professor Jay T. Lennon.
The next step was to set up experiments to determine how the minimal cells that had evolved for 300 days performed in comparison to the original, non-minimal M. mycoides as well as to a strain of minimal cells that hadn't evolved for 300 days. In the comparison tests, the researchers put equal amounts of the strains being assessed together in a test tube. The strain better suited to its environment became the more common strain.
They found that the non-minimal version of the bacterium easily outcompeted the unevolved minimal version. The minimal bacterium that had evolved for 300 days, however, did much better, effectively recovering all of the fitness that it had lost due to genome streamlining. The researchers identified the genes that changed the most during evolution. Some of these genes were involved in constructing the surface of the cell, while the functions of several others remain unknown.
Details about the study can be found in a paper recently featured in Nature. Roy Z. Moger-Reischer, a Ph.D. student in the Lennon lab at the time of the study, is first author on the paper.
Understanding how organisms with simplified genomes overcome evolutionary challenges has important implications for long-standing problems in biology—including the treatment of clinical pathogens, the persistence of host-associated endosymbionts, the refinement of engineered microorganisms, and the origin of life itself. The research done by Lennon and his team demonstrates the power of natural selection to rapidly optimize fitness in the simplest autonomous organism, with implications for the evolution of cellular complexity. In other words, it shows that life finds a way.
Fig. 1: The mutation rate and spectrum of the minimal and non-minimal
cell.
a–c, The mutation rate (per nucleotide (nt) per generation
(gen.)) and spectrum of the minimal and non-minimal cell were
estimated from mutation-accumulation experiments. a, Although
synthetic M. mycoides has the highest recorded mutation rate (base
substitutions and indels), it was not affected by genome minimization.
The dark coloured circles represent non-minimal (n = 85) and minimal
(n = 57) clones that were sequenced at the end of the experiment. The
light coloured areas represent kernel densities of the data. b,
The proportions of insertions, deletions and SNMs were also the same
for the minimal and non-minimal cells. c, Among SNMs, which
accounted for 88% of all mutations, the minimal cell exhibited a
stronger A:T bias in its mutation spectrum compared with the
non-minimal cell, particularly in the C:G to T:A category. Two-sided
χ2 analysis was used for hypothesis testing; ***P = 2.5 × 10−6 (A:T to
G:C), ***P = 1.5 × 10−11 (C:G to G:C), ***P = 1.6 × 10−20 (C:G to
T:A), ***P = 0.0003 (C:G to A:T); NS, not significant.
Fig. 2: The effect of genome minimization on fitness and
adaptation.
Genome minimization reduced the relative fitness by 50%. However,
almost all of this cost was regained over 2,000 generations of
evolution. Despite the removal of nearly half of its genome, the
minimal cell adapted at a rate comparable to that of the non-minimal
cell, which was corroborated by fitness estimates from growth curve
experiments (Extended Data Fig. 1 and Extended Data Table 1). The dark
coloured symbols represent mean ± s.e.m. As the experiment was
initiated with a single clone, error bars for the ancestral timepoint
were calculated from technical replicates (n = 4), whereas error bars
for evolved populations were calculated from replicate populations
(n = 4), both of which are depicted by light coloured symbols. The
solid red and blue lines are a visual aid connecting the mean values
of the minimal and non-minimal populations, respectively.
Fig. 3: The non-minimal cell and minimal cell populations acquired
adaptive mutations in different sets of shared genes.
Ordination from a principal coordinates analysis (PCoA) created by a
gene-by-population matrix using the Bray–Curtis distance metric after
2,000 generations of evolution (Extended Data Tables 2–4). The dashed
lines represent 95% confidence ellipses around replicate populations
(n = 4 for each cell type) represented by dark coloured symbols.
Fig. 4: The effect of genome minimization on the evolution of cell
size.
a, Genome minimization was accompanied by a 31% decrease in
cell size. Over 2,000 generations of evolution, the size of the
non-minimal cells increased by 85% (P = 0.005), whereas the size of
the minimal cells remained the same (P = 0.181). Owing to variation
associated with replicate evolved populations, there was a marginal
effect when directly comparing changes in the size of the minimal and
non-minimal cells (P = 0.077; Supplementary Fig. 4). The dark coloured
symbols represent the mean ± s.e.m. As the experiment was initiated
with a single clone, error bars for the ancestral timepoint were
calculated from samples of individuals (n = 62 and n = 75 for the
non-minimal and minimal cell, respectively), whereas error bars at the
evolved time point were calculated from individuals (n = 285 and n =
181 for the non-minimal and minimal cell, respectively) across
replicate populations (n = 4). The light coloured circles represent
randomly drawn data (n = 60) corresponding to the diameter of
individual cells from the ancestral populations. The light coloured
triangles (pointing up and down), diamonds and squares represent
randomly drawn data (n = 60) corresponding to the diameter of
individual cells from the four replicate evolved populations. The
solid red and blue lines are a visual aid connecting the mean values
of the minimal and non-minimal populations, respectively.
b,c, Scanning electron micrographs obtained from evolved
replicate populations of the non-minimal (b) and minimal
(c) cells. Scale bars, 1 μm.
Extended Data Fig. 1: Trajectories of maximum growth rates (µmax) for
the minimal cell and non-minimal cell.
Data (n = 141) were generated from growth-curve assays that were fit
using a modified Gompertz equation (see Fig. S5) across 2000
generations of experimental evolution. With these estimates of µmax,
we then fit a generalized linear mixed model (GLMM) where time
(generation) and cell type (minimal cell vs. non-minimal cell) were
treated as fixed effects and replicate evolved populations (n = 8) was
treated as a random effect. Based on the intercepts from the GLMM,
synthetic streamlining reduced µmax by 57% in the non-evolved
ancestors. During subsequent evolution, µmax for both cell types
increased at comparable rates over the course of the experiment (see
Extended Data Table 1). In the figure, dark-coloured circles represent
data from the ancestral populations, while triangles (up- and
down-pointing), diamonds, and squares represent data from the
replicate evolved populations. Dashed lines and light-coloured regions
represent predicted values and 95% confidence intervals, respectively,
for the fixed effects (generation and cell type). The conditional R2,
which accounts for variance explained by the fixed and random effects,
was 0.68. The variance partition coefficient (VPC) of 0.127 indicates
that an appreciable portion of the total explained variance in µmax
was associated with the random effect of the replicate evolved
populations (See Extended Data Table 1). Additional information,
including model fits, parameters, summary statistics, and residual
plots, can be found in the online Figshare repository.
Extended Data Fig. 2: Effect of genome streamlining on the ratio of
nonsynonymous to synonymous substitutions.
In populations of Mycoplasma mycoides after 2000 generations of
evolution, we used the normalized ratio of nonsynonymous to synonymous
mutations (dN/dS) as an indicator of natural selection. Values of
dN/dS > 1 are associated with positive selection, while values of
dN/dS < 1 are associated with the dominance of negative selection
and constraint on adaptation. The minimal and non-minimal cell
exhibited comparable values of dN/dS (t6 = 0.81, P = 0.488). One of
the replicate populations belonging to the non-minimal treatment had
an elevated dN/dS (2.06) compared to other replicate populations (mean
dN/dS = 0.45). When we removed this potential outlier, there was still
no difference in dN/dS between the minimal and non-minimal cell
(t5 = −0.25, P = 0.811). Dark-coloured symbols represent the mean ±
SEM (n = 4). Light-coloured symbols represent individual values for
each replicate population (n = 4). Hypotheses were evaluated with
two-sided t-tests.
Extended Data Fig. 3: Fitness effects of an
ftsZ mutation on populations of
Mycoplasma mycoides.
We reengineered the nonsense mutation ftsZ E315* and quantified
its effect on relative fitness in both the non-minimal and minimal
cells using head-to-head competition assays. The ftsZ E315*
nonsense mutation had a significant effect on Mycoplasma cell
size that depended on cell type (two-way ANOVA, F1,32 = 7.45,
P = 0.010). Compared to the wild type (non-evolved ancestor), the
mutation increased relative fitness by 25% in the non-minimal cell and
14% in the minimal cell. Dark-coloured symbols represent the mean ±
SEM. Light-coloured symbols represent values for each replicate
population. Samples sizes are as follows: wild-type minimal cell,
n = 12; ftsZ E315* minimal, n = 12; wild-type non-minimal cell,
n = 5; ftsZ E315* non-minimal, n = 5.
Extended Data Fig. 4: Cell size of ftsZ mutants
compared to wildtype (non-evolved) for the minimal cell and
non-minimal cell.
Using scanning electron microscopy, the ftsZ E315*
nonsense mutation had a significant effect on Mycoplasma cell
size that depended on cell type (two-way ANOVA, F1,241 = 37.9, P <
0.0001). The mutation in the non-minimal cell caused a 25% increase in
cell diameter (P < 0.0001) and a corresponding two-fold increase in
cell volume. In contrast, the same ftsZ nonsense
mutation in the minimal cell led to a 19% decrease in the cell
diameter (P = 0.015). Dark-coloured symbols represent mean ± SEM.
Light-coloured symbols represent randomly drawn data (n = 60)
corresponding to the diameter of individual cells.
AbstractWhat we can expect now is for creationists to try to get away with redefining evolution, which science defines as change in the allele frequency in the genome of a population over time, and insist evolution means changing into a new species altogether or at least growing legs and arms.
Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life1,2. Here we report on how an engineered minimal cell3,4 contends with the forces of evolution compared with the Mycoplasma mycoides non-minimal cell from which it was synthetically derived. Mutation rates were the highest among all reported bacteria, but were not affected by genome minimization. Genome streamlining was costly, leading to a decrease in fitness of greater than 50%, but this deficit was regained during 2,000 generations of evolution. Despite selection acting on distinct genetic targets, increases in the maximum growth rate of the synthetic cells were comparable. Moreover, when performance was assessed by relative fitness, the minimal cell evolved 39% faster than the non-minimal cell. The only apparent constraint involved the evolution of cell size. The size of the non-minimal cell increased by 80%, whereas the minimal cell remained the same. This pattern reflected epistatic effects of mutations in ftsZ, which encodes a tubulin-homologue protein that regulates cell division and morphology5,6. Our findings demonstrate that natural selection can rapidly increase the fitness of one of the simplest autonomously growing organisms. Understanding how species with small genomes overcome evolutionary challenges provides critical insights into the persistence of host-associated endosymbionts, the stability of streamlined chassis for biotechnology and the targeted refinement of synthetically engineered cells2,7,8,9.
Moger-Reischer, R.Z., Glass, J.I., Wise, K.S. et al.
Evolution of a minimal cell.
Nature (2023). https://doi.org/10.1038/s41586-023-06288-x
Copyright: © 2023 The authors.
Published by Springer Nature Ltd. Open access
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
What this research shows though is that even when severely constrained with a limited genome and so limited opportunities for evolution, self-replicating organisms in a selective environment will inevitably evolve towards greater fitness in that environment. These organisms even evolved to reduce the constraints they were evolving under.
In just 2,000 generations, evolution was observable and measurable and confirmed as well as anything that evolution can and does occur, naturally and without supernatural interference. The research also shows that the biologists had no difficulty applying the Theory of Evolution to explain their observations. There were no reports of any doubt or instances of magic being observed to have caused anything to happen.
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