[math-fun] 473-gene "artificial bactierium"
Venter et al made their long-awaited "artificial bacterium" (actually synthetic DNA that they managed to get inside a bacterium to "boot up" a wholy artificial design for living being, which of course was based on 473 known natural genes). They think or hope that 473 is near minimum possible. -- Warren D. Smith http://RangeVoting.org <-- add your endorsement (by clicking "endorse" as 1st step)
How many base-pairs?
Sent: Sunday, March 27, 2016 at 4:41 PM From: "Warren D Smith" <warren.wds@gmail.com> To: math-fun <math-fun@mailman.xmission.com> Subject: [math-fun] 473-gene "artificial bactierium"
Venter et al made their long-awaited "artificial bacterium" (actually synthetic DNA that they managed to get inside a bacterium to "boot up" a wholy artificial design for living being, which of course was based on 473 known natural genes).
They think or hope that 473 is near minimum possible.
-- Warren D. Smith http://RangeVoting.org <-- add your endorsement (by clicking "endorse" as 1st step)
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A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us. 2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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You would need a selection for small genome size to get evolution to work on this. While there is a built-in selection for size in that the doubling time is partially paced by genome replication, it is not a sharp selection. Genome replication is heavily pipelined, with 8 copies of the origin of replication and 1 copy of the terminus in rapidly growing coli cells. Also, the 570 kb genome is lacking in a huge number of genes that would normally be considered essential, such as all of the amino acid synthesis genes, all of the fatty acid synthesis genes, all of the nucleotide synthesis genes etc., so the experiment would have to be carried out in a very rich medium containing all of those compounds. Not impossible, and the good news is that likely no one has tried it. But knockouts of genes typically disable them, but don’t remove them. Coli is stable over hundreds of thousands or millions of replication cycles in continuous culture.
On May 12, 2016, at 1:38 PM, Allan Wechsler <acwacw@gmail.com> wrote:
A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us.
2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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I did not express myself well, if it wasn't clear that I was proposing explicitly measuring and selecting for genome size. A sketch of the experimental procedure: Grow the organism in ten culture tanks. (The medium should be fixed at the start of the experiment. I expect different results depending on medium.) Ever so often (twelve hours, maybe?) grab a sample from each tank, and use it to "weigh" the genome by electrophoresis; use this data to identify the culture with the smallest average genome. Dump all the cultures except the best; restart the ten tanks with seeds from the best tank. Repeat thousands of times. On Thu, May 12, 2016 at 1:58 PM, Tom Knight <tk@ginkgobioworks.com> wrote:
You would need a selection for small genome size to get evolution to work on this. While there is a built-in selection for size in that the doubling time is partially paced by genome replication, it is not a sharp selection. Genome replication is heavily pipelined, with 8 copies of the origin of replication and 1 copy of the terminus in rapidly growing coli cells. Also, the 570 kb genome is lacking in a huge number of genes that would normally be considered essential, such as all of the amino acid synthesis genes, all of the fatty acid synthesis genes, all of the nucleotide synthesis genes etc., so the experiment would have to be carried out in a very rich medium containing all of those compounds. Not impossible, and the good news is that likely no one has tried it. But knockouts of genes typically disable them, but don’t remove them. Coli is stable over hundreds of thousands or millions of replication cycles in continuous culture.
On May 12, 2016, at 1:38 PM, Allan Wechsler <acwacw@gmail.com> wrote:
A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us.
2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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I think with this methodology you could easily exert evolutionary pressure in favor of small *organisms*. But even in a bacterium, the mass of its DNA is <1% of the total mass. So selecting for genome length seems hard. --Michael On Thu, May 12, 2016 at 2:27 PM, Allan Wechsler <acwacw@gmail.com> wrote:
I did not express myself well, if it wasn't clear that I was proposing explicitly measuring and selecting for genome size. A sketch of the experimental procedure:
Grow the organism in ten culture tanks. (The medium should be fixed at the start of the experiment. I expect different results depending on medium.) Ever so often (twelve hours, maybe?) grab a sample from each tank, and use it to "weigh" the genome by electrophoresis; use this data to identify the culture with the smallest average genome. Dump all the cultures except the best; restart the ten tanks with seeds from the best tank. Repeat thousands of times.
On Thu, May 12, 2016 at 1:58 PM, Tom Knight <tk@ginkgobioworks.com> wrote:
You would need a selection for small genome size to get evolution to work on this. While there is a built-in selection for size in that the doubling time is partially paced by genome replication, it is not a sharp selection. Genome replication is heavily pipelined, with 8 copies of the origin of replication and 1 copy of the terminus in rapidly growing coli cells. Also, the 570 kb genome is lacking in a huge number of genes that would normally be considered essential, such as all of the amino acid synthesis genes, all of the fatty acid synthesis genes, all of the nucleotide synthesis genes etc., so the experiment would have to be carried out in a very rich medium containing all of those compounds. Not impossible, and the good news is that likely no one has tried it. But knockouts of genes typically disable them, but don’t remove them. Coli is stable over hundreds of thousands or millions of replication cycles in continuous culture.
On May 12, 2016, at 1:38 PM, Allan Wechsler <acwacw@gmail.com> wrote:
A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us.
2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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-- Forewarned is worth an octopus in the bush.
Again, I was insufficiently clear. It is possible to extract the DNA and weigh just that, using various limited-permeability techniques. I did not mean to suggest weighing the whole organism. On Thu, May 12, 2016 at 2:38 PM, Michael Kleber <michael.kleber@gmail.com> wrote:
I think with this methodology you could easily exert evolutionary pressure in favor of small *organisms*. But even in a bacterium, the mass of its DNA is <1% of the total mass. So selecting for genome length seems hard.
--Michael
On Thu, May 12, 2016 at 2:27 PM, Allan Wechsler <acwacw@gmail.com> wrote:
I did not express myself well, if it wasn't clear that I was proposing explicitly measuring and selecting for genome size. A sketch of the experimental procedure:
Grow the organism in ten culture tanks. (The medium should be fixed at the start of the experiment. I expect different results depending on medium.) Ever so often (twelve hours, maybe?) grab a sample from each tank, and use it to "weigh" the genome by electrophoresis; use this data to identify the culture with the smallest average genome. Dump all the cultures except the best; restart the ten tanks with seeds from the best tank. Repeat thousands of times.
On Thu, May 12, 2016 at 1:58 PM, Tom Knight <tk@ginkgobioworks.com> wrote:
You would need a selection for small genome size to get evolution to work on this. While there is a built-in selection for size in that the doubling time is partially paced by genome replication, it is not a sharp selection. Genome replication is heavily pipelined, with 8 copies of the origin of replication and 1 copy of the terminus in rapidly growing coli cells. Also, the 570 kb genome is lacking in a huge number of genes that would normally be considered essential, such as all of the amino acid synthesis genes, all of the fatty acid synthesis genes, all of the nucleotide synthesis genes etc., so the experiment would have to be carried out in a very rich medium containing all of those compounds. Not impossible, and the good news is that likely no one has tried it. But knockouts of genes typically disable them, but don’t remove them. Coli is stable over hundreds of thousands or millions of replication cycles in continuous culture.
On May 12, 2016, at 1:38 PM, Allan Wechsler <acwacw@gmail.com> wrote:
A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us.
2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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-- Forewarned is worth an octopus in the bush. _______________________________________________ math-fun mailing list math-fun@mailman.xmission.com https://mailman.xmission.com/cgi-bin/mailman/listinfo/math-fun
I don't think it's been done with a bacterium, but it's been done with an RNA virus replicating in the presence of mono-nucleotides. They started with a viral RNA of 4500 base pairs and found an "optimized" one of 220. I think this is the paper, but I don't have access to it. Wagner, A., and P. F. Schuster. 1999. Viral RNA and evolved mutational robustness. J. Exp. Zool. 285:119-127 Brent On 5/12/2016 10:38 AM, Allan Wechsler wrote:
A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us.
2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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There was one study that was done with bare RNA replicating in the presence of RNA polymerase and a free supply of mononucleotides. There was no selection pressure except, sort of, what the polymerases liked to copy. Under a wide range of initial conditions, it zeroed in on a little fragment that basically just had polymerase binding sites. See "Spiegelman's Monster". But this doesn't say anything about the minimal genome required to make a cellular living from, say, the minimal glucose+salts medium. On Thu, May 12, 2016 at 6:07 PM, Brent Meeker <meekerdb@verizon.net> wrote:
I don't think it's been done with a bacterium, but it's been done with an RNA virus replicating in the presence of mono-nucleotides. They started with a viral RNA of 4500 base pairs and found an "optimized" one of 220. I think this is the paper, but I don't have access to it.
Wagner, A., and P. F. Schuster. 1999. Viral RNA and evolved mutational robustness. J. Exp. Zool. 285:119-127
Brent
On 5/12/2016 10:38 AM, Allan Wechsler wrote:
A very late reply to this interesting thread. I am curious to know whether any biologists have tried letting evolution do this work: that is, breed some well-understood model organism (almost certainly E. coli K12 or something similar) and select for small genome. I think genome size can be easily calculated by electrophoresis. This ought to be easy to mechanize, and with a generation time of 17 minutes I suspect that evolution would start whittling away at the 4.6 Mbp genome pretty quickly. Leave it running for a few months and see how close it can get to this 531 Kbp goal line. I have a sneaking suspicion that it would surprise us.
2016-03-27 13:02 GMT-04:00 Warren D Smith <warren.wds@gmail.com>:
http://www.livescience.com/54165-artificial-bacterium-has-smallest-genome.ht...
531K base pairs.
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participants (6)
-
Adam P. Goucher -
Allan Wechsler -
Brent Meeker -
Michael Kleber -
Tom Knight -
Warren D Smith