On the afternoon of the second day of NSF’s Minimal Life workshop, Eric Smith of the Santa Fe Institute in New Mexico provided a much-needed synthesis.
He examined the trade-offs of having a super-pared-down genome and the need to leech off of the environment — parasites, for example, can only survive with bare-bones genomes because they farm out most of their metabolic needs to their hosts. He presented his not surprising, but necessary, quantitative data showing that the more dependent an organism is on its environment, the less metabolically complete its own genome is.
Smith discussed the metabolic and biosynthetic pathways that seem to be universally needed for life, which all involve the same five precursors (the famous CHNOPS from high school chemistry), the same cofactors, and produce pretty much the same amino acid nucleotides. But while it’s hard to find the complete networks for all these necessary bits and pieces at the level of an individual species, they are indeed wrapped into a nice little package at the level of the ecosystem. The boundary between organism and ecosystem, then, is more fluid and less important than most people assume.
“What species lineages are doing is breaking up the universal metabolic costs, and creating behavioral links that allow species to get what they don’t make within an ecosystem,” he said. Even the cell theory of life, Smith says, is “not as fundamental as we take it to be”.
Andy Ellington from University of Texas in Austin was next, and, following his discussion yesterday, opened with a diatribe against the concept of life. As “the only person in the room from the deep south…where people think differently”, he said he understood the consequences of the word’s sentimentality, which was due in part to the difficulty of defining it.
“For me, life is like pornography,” he said. “We know it when we see it, but we can’t actually define it with any precision.”
But that didn’t stop him from commenting on “the magic of life”: that complex function arises from the interaction of simple components. To understand the black box in between, he’s trying to create the minimal artificial system capable of evolving, a process which even viruses are capable of.
“I’m a genomic emperialist,” he said. “If T4 [virus] DNA gets in [a host cell], makes more T4 DNA, and gets out, it’s doing its job. It replicates. Whether I call carbon and nitrogen and some water my home or a big bag of nucleotides and enzymes and other fun things my home, it doesn’t matter to me. My DNA replicates.”
Thus he removes a pesky hurdle that holds back many bottom-up, engineering approaches to biology: the cell. “I don’t like the cell,” he said, “and I don’t think it makes any difference whether you have a cell or not to think about these things.”
Instead, he’s trying to engineer his evolvers in in vitro replicating systems — droplets of watery solution bobbing in a sea of mineral oil. Each droplet has the basics for DNA transcription and translation, and gets an evolutionary nudge from a self-splicing intron that jumps around the genome disrupting code, and can even do so in a targeted fashion.
To test the ability of his ascetic droplet worlds to support protein evolution, he provided genes for streptavidin and biotin, which normally bind very tightly. He scrambled the biotin binding site of streptavidin and distributed different mutants among some 10^12 little droplets. The system “responded like a champ,” he said, evolving novel interactions between the proteins.
Moreover, these novel proteins, which had “never seen the inside of a cell, just the black oily night, for their entire evolutionary lives”, were more soluble than wild-type proteins in the in vitro system. The protein had learned to fold better in its oily environment than in a cell.
One novel binding site is all well and good, but Ellington wants to “take my pathetic little one-feedback loop and extend it out” by evolving an operon or even an enzyme that amplifies its own gene.
“The goal is to make increasingly complex replicators that have nothing to do with cells, but have replicating functionality,” he said. “It’s a subsystem of a cell but it evolves.”
Ellington concluded that these replicators that undergo evolution “challenge the intuition that cells are important for life”. He also pointed out to Smith that, contrary to his discussion, “there’s no ecosystem here. It’s its own selfish self, trying to make more of its own selfish self. It is what it is.”
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