Sciencemadness Discussion Board - A L I E N , D N A

A L I E N , D N A

franklyn - 27-1-2020 at 04:30

I'm very very surprised no one caught on to this here !
It's been in the works for years and achieved just 4 years ago

It began with two , two more that is , six total.

Bacterium with six DNA letters engineered
www.youtube.com/watch?v=P5Fu6giB6eo

www.youtube.com/watch?time_continue=244&v=Xp9HEp4cYzM&am...

The whole story
www.youtube.com/watch?time_continue=11&v=-H1tUMRJoeo&...

The X-Files : Season 1 , Episode 24 , “ The Erlenmeyer Flask ” premiered May 13, 1994
Dr.Carpenter hands Scully the completed analysis of bacteria that reveals a startling conclusion concerning some anomalous data :
“ A fifth and sixth DNA nucleotide. A new base pair. Agent Scully , what you are looking at exists nowhere in nature. It would have to be , by definition extraterrestrial.”
Scroll forward to time 20:00 , watch for a minute
www.dailymotion.com/video/x61szuo

Wait for it , now it's four more , eight total. P , Z and B , S augment C , G and A ,T

Synthetic DNA Made With 4 Additional Letters
www.sciencealert.com/scientists-made-synthetic-dna-using-8-l...

An expanded 8-letter DNA genetic code created
www.youtube.com/watch?v=t-nmB-r6Eug

This is not just playing God , this is being God , and that's being gracious. Synthetic biology invents new ways to monkey with the fundamentals of life. Monkey is the operative word because one must do the experiment to know what can happen.

A mad scientist is one who experiments on himself.
A scientist who experiments on other people is called a pioneer.
— Me

It's not what you don't know that gets you into trouble.
It's what you think you know for sure that just ain't so.
— Mark Twain ( Samuel Clemens )

.

j_sum1 - 27-1-2020 at 14:20

I saw this ages ago. This is basically tinkering. Interesting but not really of much significance.
All that has happened is the development of some base pairs that are compatible with the DNA helix. It is not like they code for anything.

Now if someone was to develop messenger RNA and tRNA such that it bonded on to alternate amino acids that are not currently coded for...
And this tRNA and new amino acids were compatible with the ribosomes so that protein chains could be produced...
And the resultant chain was also able to be folded into a protein...
And these new proteins could be engineered to have some function

Then we would have something of biological significance.

Until then all we have is new lego bricks that don't actually connect with anything.

andy1988 - 27-1-2020 at 14:42

There are arguments that there is a loss of search efficiency with additional possible letters, and it is most efficient the way things are structured now.

I liked the study where they used dietary restriction and natural selection to induce a letter/pair change in E Coli IIRC. Clever stuff.

I do like this research as evidence that life elsewhere in the universe with chemistry/structure significantly different from our own is possible.

karlos³ - 27-1-2020 at 14:49

But the most important thing is: can we eat these aliens with a differentally structured DNA?
Because I would like to eat the aliens whenever we get to see some.
I recently read the novel Proxima by Stephen Baxter, and boy, I really got hungry by certain descriptions of these inedible aliens!

Fulmen - 27-1-2020 at 14:51

Quote: Originally posted by j_sum1

new lego bricks that don't actually connect with anything.

Well put. it's interesting work, but it's not life (as we know it, Jim). It's like adding letters to the alphabet...

Tsjerk - 27-1-2020 at 15:06

Quote: Originally posted by j_sum1

Now if someone was to develop messenger RNA and tRNA such that it bonded on to alternate amino acids that are not currently coded for...
And this tRNA and new amino acids were compatible with the ribosomes so that protein chains could be produced...
And the resultant chain was also able to be folded into a protein...
And these new proteins could be engineered to have some function

Then we would have something of biological significance.

Completely right. If you would get all of that done you would probably win two or three Nobel prizes along the road.

I had a look at this in 2013 when coming up with an iGEM project, the problems you are going to face are numerous which are also uneasy to overcome to say the least.

OKay, assuming the new DNA is now made and not wrongly recognized by DNA'ses. It has to be recognized by transcriptases, and correctly transcribed to RNA. I don't think there is anyone in the world who would have more than a vague idea how to do this.

Next, you have to translate the new RNA to protein. Please have a talk with the guys who crystallized the ribosome. They got a Nobel prize for doing so, they will tell you a "wrong" triplet won't fit and you need a shit ton of engineering to make a new one fit to do something useful. Any cell, also the first bacteria, are very good at recognizing the wrong stuff, therefore the existence of RNA'ses. Good luck with those as well.

Also you need new tRNA to connect the new amino acids. Good luck engineering that.

Next proteins with new amino acids need those amino acids to be available in the cytosol... Either they are newly synthesized by the host or imported. The easiest would be to use an amino acid that is not toxic and co-imported by default via an existing transporter, or some AA that is already available. Designing a new transporter would be mad mans work. I would love to see an example of a designer transporter.

Edit: I forgot about the caspases, you definitely need them to aid the new proteins to be formed. So you need to design them as well

Edit: Also don't forget about the proteases, you would have to knock out those that degrade your protein of interest or any of the above mentioned engineered proteins.

Edit: you also have to do all the modifications mentioned above without killing the host.... All the functionalities are there for a reason.

[Edited on 27-1-2020 by Tsjerk]

SWIM - 27-1-2020 at 15:18

Quote: Originally posted by karlos³

But the most important thing is: can we eat these aliens with a differentally structured DNA?
Because I would like to eat the aliens whenever we get to see some.
I recently read the novel Proxima by Stephen Baxter, and boy, I really got hungry by certain descriptions of these inedible aliens!

A scene a few years from now:

It is a bright sunny day, and an alien with a terror stricken look in his eyes is running through the streets.
He has just managed to translate Karlos' new book, How To Serve The Reptiloids From Zeta Reticuli.
He waves the book over his head and shouts again and again, "It's a cookbook! It's a cookbook!"

karlos³ - 27-1-2020 at 15:35

You're totally wrong, it would be "how to serve the stick people from proxima C", and it won't be a cook book, it will be a culinary aficionado manual!

Not just a plain cook book... can't make it too easy for the alien people!

mayko - 27-1-2020 at 16:40

RIP Deep Throat.

A subtlety here is that, even within extant life, additional nucleotides are neither necessary nor sufficient for non-standard amino acids!

Amino acids are often altered with various sidechains after they have been incorporated into the polypeptide chain, a process called "post-translational modification". The same codon represents the vanilla and derived amino acid in the DNA sequence. Another example is selenocysteine, a selenium analog of the standard amino acid cysteine. It is encoded by a repurposed stop codon plus an untranslated regulatory sequence.

As far as extra nucleotides.... one regulatory mechanism is DNA methylation, in which methyl groups are added to nucleotides. Methyl cytosine doesn't add any special coding potential though; it's more like a sticky note on the DNA that says "disregard this". Another example is adenosine deamination of mRNA, in which an enzyme converts some adenosines into inosines. This can have regulatory effects, but it can also alter the protein product, because the inosine is read by the translational machinery as a guanine. This can change the amino acid coding for, but doesn't add to the amino acid repertoire.

A few years ago this paper came out that blows my mind anew each time I read it. It looks like octopi have evolved such that A-to-I editing and its regulation provides a lot of the variation in their proteome, rather than explicit coding sequences hardwritten in the DNA.

https://www.mbl.edu/blog/smart-cephalopods-trade-off-genome-...

https://www.cell.com/fulltext/S0092-8674(17)30344-6

Tsjerk - 27-1-2020 at 23:30

You could also have a look at non-ribosomal peptide synthesis. Nature has ways to produce pretty cool stuff.

https://www.researchgate.net/figure/Nonribosomal-peptide-syn...

pneumatician - 12-3-2020 at 14:01

DNA? who need DNA?

https://www.youtube.com/results?search_query=red+rain+in+ker...

https://sites.google.com/site/asanthoshkumar70/what-s-new-in...

mayko - 10-4-2020 at 14:22

Fischer, E. C., Hashimoto, K., Zhang, Y., Feldman, A. W., Dien, V. T., Karadeema, R. J., … Romesberg, F. E. (2020). New codons for efficient production of unnatural proteins in a semisynthetic organism. Nature Chemical Biology, 1–8. https://doi.org/10.1038/s41589-020-0507-z

Quote:

Natural organisms use a four-letter genetic alphabet that makes available 64 triplet codons, of which 61 are sense codons used to encode proteins with the 20 canonical amino acids. We have shown that the unnatural nucleotides dNaM and dTPT3 can pair to form an unnatural base pair (UBP) and allow for the creation of semisynthetic organisms (SSOs) with additional sense codons. Here, we report a systematic analysis of the unnatural codons. We identify nine unnatural codons that can produce unnatural protein with nearly complete incorporation of an encoded noncanonical amino acid (ncAA). We also show that at least three of the codons are orthogonal and can be simultaneously decoded in the SSO, affording the first 67-codon organism. The ability to incorporate multiple, different ncAAs site specifically into a protein should now allow the development of proteins with novel activities, and possibly even SSOs with new forms and functions.

the bibliography looks like a good reading list as well......

Attachment: Fischer et al. - 2020 - New codons for efficient production of unnatural proteins in a semisynthetic organism.pdf (1.8MB)
This file has been downloaded 728 times

Metacelsus - 10-4-2020 at 14:45

Interesting paper. I'm surprised Romesberg is still publishing after being fired from Scripps for sexual harassment . . .

mayko - 10-4-2020 at 15:38

Yikes!!! I missed that.

When our creeper got kicked out of the department there was still a trickle of publications that technically had his name on it, as some of his grad students wrapped up research from under his mentorship.

I wasn't in on the whisper network and no one would say out loud why his lab was emptying and all the equipment being set out for the taking. Of course I was like "Hey, free lab stuff! I love free lab stuff!" Now I have a bunch of bottles and such with his name written on them and I worry my lab is going to be haunted by the malevolent spirit of a sex pest

Metacelsus - 11-4-2020 at 05:14

Ironically, I was seriously considering working for him at Scripps, since I was interested in his research. I visited his lab and talked to him and his students, and everything seemed OK. I'm glad I didn't go there!

Currently one of my research projects is genetic recoding using engineered tRNAs and ribosomes The idea is to change the CCA acceptor arm of the tRNAs to something else (which the native ribosome won't recognize) and then add engineered ribosomes which recognize it. Basically this would set up a different translation system working in parallel to the natural one. There are a few other tricks required to get this to work though.