Synthetic Life: Most Minimalist Microorganism
J. Craig Venter is in the news again. He and his team at Synthetic Genomics have created a synthetic organism with a viable genome smaller than anything that evolved the old-fashioned way.
If you don’t remember Venter, he’s best known for being the lead guy of the private-sector’s efforts to sequence the human genome for the first time. He also created the first “synthetic life” of sorts back in 2010.
That landmark work in 2010 synthetically re-created the genome of a bacterium called Mycoplasma mycoides from what was essentially 4 bottles of chemicals. The researchers then transplanted that synthetic genome into another bacterium, Mycoplasma capricolum. That new bacterial genome then took over the cell and started to thrive and reproduce. This was called Syn1.0.
Having never been done before, that achievement was big news for synthetic life fans. Still it was only a proof of concept that was only a first step. Their longer term goal was to create a living organism with the fewest number of genes possible to allow it to sustain itself and reproduce…the most basic components for life if you will. All else arguably being just window dressing I suppose.
To that end, they started with syn1.0 and started removing genes based on what conventional thought deemed superfluous. Those attempts failed. Their next strategy was to split the genome into 8 segments, remove some genes and see if the resulting cell survived once they were all recombined. If it didn’t, then they clearly removed something critical. Eventually they successfully created syn2.0 with the smallest genome of any natural cell. Now syn3.0 has even fewer.
To put this in perspective, most bacteria have 4,000 to 5,000 genes to control all their day-to-day BTDL or Bacterial To Do List. The parasitic Mycoplasma genitalium (!!!!!) bacteria has the smallest genome we’ve ever found: 525 genes. Syn3.0 contains just 473 genes.
But that’s not even the coolest thing. Let’s look at the broad categories of what those 473 genes do:
- They preserve genome information through activities like DNA replication, repair, cell division etc
- They obsess over cell membrane structure and function and control the cytoplasm inside.
- After all that, there’s 149 genes left. What do they do? WE HAVE NO IDEA!
That’s right. 31.5% of the genes in Syn3.0 are little black boxes. We know very little or nothing about what they actually do. We do know however that many are highly conserved. This means that they are found in almost identical form in many other, vastly different, organisms. For such genes to remain unchanged for so long implies that they server some critical function that evolution did not want to fuck with.
Adam Arkin, the director of the Berkeley Synthetic Biology Institute said the researchers found…
“a huge number of surprises even in that minimal genome which couldn’t have been found by looking at genome sequences…It is a profound result and very elegantly presented.”
Another interesting result of this research is the potential implication of what Venter’s team also did to the cell DNA. They reorganized it. They made it more simple, modular, and organized.
Christopher Voigt, a professor of biological engineering at the Massachusetts Institute of Technology has an interesting take on this fact:
“If human designers can create an ordered, structured alternative to how life is found in nature, that would speak to the complexity of biology simply being an artifact of how it was shaped by evolution.”
Clearly this work is not done. There are hints that synX.0 could eventually be pared down to well below 473 genes. Perhaps something around 280. If this is in the range of minimum genes for a life form, that would truly be an achievement. Once that is accomplished and we also understand the function of all of those two hundred and eighty some-odd genes….well, who know what might come from that. Certainly, it would help us to engineer new, never-before-seen, metabolic pathways that could perform amazingly useful tasks like breaking down contaminants or excrete biofuels.
I haven’t even touched upon the potential of multi-cellular synthetic life. I think I’ll leave that for a future post.
Image Credit: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy Research at the University of California at San Diego)