Hi, thanks, and very cool work (assuming it eventually holds up in peer review)!
A few things that confused me while trying to read the paper:
- There's two different methods of cell division mentioned -- mechanical extrusion and the autonomous, protein-driven division. Most of the results (e.g. the five generations) focus on the mechanically driven one, while the autonomous one is more "lifelike". Does the autonomous division have a higher failure rate, or can you get the same results with it as well?
- It's mentioned that the bottleneck for survival of many generations is ribozomes degrading, but also that ribozomes are supplied from the outside. Do the degraded ribozomes actively harm the cell? Or is there some other reason why they cannot be replenished?
- You say that after 5 generations, only 30% of the cells have the correct genome, and it's presented like a problem -- but 30% of 2^5 is more than 10, so this sounds like more than enough for continued survival. Is there something missing in this train of thought? Perhaps other failures that can kill the cell?
And some questions about the implications:
- Do you think that the genome you use is already close to minimal? AFAIK a lot of the minimal organisms found in the wild are parasites of some sort, getting most of their complex molecules from the outside, which is a similar spirit to this (a rich medium and the cell "just" self-duplicating). If the multiple plasmids are causing trouble (per the previous point), would it make sense to try and get rid of some of them?
- Are those minimal genes somehow interpretable -- as in "you need functions X, Y, and Z and cannot avoid them by using a better medium"?
- Do you think this is a plausible stage of very early life?
A few things that confused me while trying to read the paper:
- There's two different methods of cell division mentioned -- mechanical extrusion and the autonomous, protein-driven division. Most of the results (e.g. the five generations) focus on the mechanically driven one, while the autonomous one is more "lifelike". Does the autonomous division have a higher failure rate, or can you get the same results with it as well?
- It's mentioned that the bottleneck for survival of many generations is ribozomes degrading, but also that ribozomes are supplied from the outside. Do the degraded ribozomes actively harm the cell? Or is there some other reason why they cannot be replenished?
- You say that after 5 generations, only 30% of the cells have the correct genome, and it's presented like a problem -- but 30% of 2^5 is more than 10, so this sounds like more than enough for continued survival. Is there something missing in this train of thought? Perhaps other failures that can kill the cell?
And some questions about the implications:
- Do you think that the genome you use is already close to minimal? AFAIK a lot of the minimal organisms found in the wild are parasites of some sort, getting most of their complex molecules from the outside, which is a similar spirit to this (a rich medium and the cell "just" self-duplicating). If the multiple plasmids are causing trouble (per the previous point), would it make sense to try and get rid of some of them?
- Are those minimal genes somehow interpretable -- as in "you need functions X, Y, and Z and cannot avoid them by using a better medium"?
- Do you think this is a plausible stage of very early life?