Biology Reference
In-Depth Information
THE EVOLUTION OF COOPERATION CAN YIELD NOVEL BEHAVIORS
IN SYNTHETIC CONSORTIA
Studies of engineered consortia have demonstrated that two distinct populations can evolve
a novel, cooperative behavior in a relatively short period of time. While such evolvability
has implications in the construction of consortia for medical and industrial applications, it
can also address questions regarding the evolution of symbiosis and cooperation.
14
Shou et al.
21
examined evolvability of a cooperative consortium by creating two auxotophic
yeast strains: one which requires adenine to grow and the other which requires lysine to
grow. When the two strains were cocultured in a minimal medium, they were unable to
exchange sufficient amounts of essential metabolites to sustain growth of either strain.
To create a cooperative consortium, the authors engineered each strain to overproduce the
amino acids required by the other strain. That is, the adenine auxotroph overproduces lysine
and the lysine auxotroph overproduces adenine. When cocultured, each overproducing
strain was able to supply sufficient metabolites to the opposing population, and thus the
consortium cooperated and grew. Using a mathematical model, the authors predicted that a
critical factor in determining whether the consortium would grow depended upon the initial
densities of each population. When each population was inoculated at a sufficiently low
density, the consortium was not viable. However, if both populations were inoculated at a
sufficiently high density, the consortium grew. Interestingly, the authors observed that when
the consortium was cultured and sequentially diluted (i.e. bottlenecked) over extended
periods of time (
70 generations), the initial population density required for viability of the
consortium was reduced. Specifically, prior to long-term culturing, 10
3
B
10
4
cells/mL were
required for a viable consortium, whereas after long-term culturing, 10
1
10
2
cells/mL could
initiate a viable consortium.
Recently, Hosoda et al. determined a potential mechanism by which auxotrophic
cooperation could emerge in a synthetic consortium.
43
The authors engineered two
auxotrophic
E. coli
strains: an auxotrophic isoleucine strain (I-) and an auxotrophic leucine
strain (L-). When grown independently, neither strain grew in a minimal medium, nor
could either strain supply sufficient metabolites to support the other population
255
s growth.
That is, the L- strain could not produce and secrete sufficient isoleucine to rescue the growth
of the I- strain, and vice versa. Surprisingly, however, when cocultured in a well-mixed
minimal medium, the consortium could cooperate and grow, thus suggesting sufficient
production and metabolite exchange. Growth measurements revealed that the I- strain
grew first. This suggested that the L- population supplied isoleucine initially to rescue I-,
whereupon growth of I- rescued the L- strain. Interestingly, the isoleucine supply from the
L- population was sufficiently high to allow the I- population to grow two-fold higher than
the L- population. Furthermore, the concentration of isoleucine in the medium was
significantly greater than when the L- population was grown in monoculture. This suggested
that, upon interaction with the I- population, the L- population began to oversupply isoleucine.
'
To understand how the L- population became an apparent oversupplier of isoleucine
upon coculture with the I- population, the authors examined the transcriptional profiles
of both populations after coculture. Several categories of genes were up-regulated in the
L- population (amino acid biosynthesis of tryptophan, proline, methionine, phenylalanine,
leucine, cysteine, and chorismate, the precursor to the aromatic amino acids), while a few
were down-regulated (pathways for catabolism including tricarboxylic acid cycle, fatty acid
oxidation). Expression of genes regulating isoleucine biosynthesis and transport remained
unchanged. As such, while it appeared that the direct up-regulation of isoleucine production
did not contribute to the mechanism of enhanced cooperation, an overall increase in
amino acid anabolism was detected, suggesting its role in the oversupplier phenotype. The
authors suggested two plausible explanations for their results. First, a small population of
isoleucine oversuppliers existed in the initial inoculum and was enriched for during growth.
