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Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

bioinformatics.stackexchange.com

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Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#111

Post by samus »

userbinator wrote: post #91
subroutine wrote: post #24

Earlier quoted context omitted.

Adding a poly(A) tail when engineering rna plasmids is so common that it's part of the standard feature library of most plasmid editors. Here I have a screenshot of the ApE editor displaying one plasmid I made for a neurobio experiment involving the overexpression of two chimeric proteins (actin and profilin, respectively linked to green and red fluorophores; note the editor has autotagged the polyA tail feature): ht…

Looks almost like a hex editor.

It kind of is. We are not quite advanced enough to have the equivalent of true programming languages for genetics.

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#112

Post by eropple »

sublinear wrote: post #101
xg15 wrote: post #99

Earlier quoted context omitted.

As a coder, I find it a bit frustrating how often explanations in biology contain fuzzy phrases like "plays a role in" or "is required for" or "works together with" or "modulates the activity of" - without ever expected what role it plays, why it is required or how it works together. So props to them for going a bit more into detail here - and also highlighting that the reason for the fuzzy phrases can often be that…

I think you'll find similar bullshittery in the details of every topic that isn't math. Think of it like finding "TODO" comments in old code.

I mean, historically mathematics have had areas full of "HACK:" comments, too--ones retroactively applied to the whole of Newtonian physics, even, but it's still useful enough that we keep it around!

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#114

Post by af3d »

eropple wrote: post #112
sublinear wrote: post #101

Earlier quoted context omitted.

I think you'll find similar bullshittery in the details of every topic that isn't math. Think of it like finding "TODO" comments in old code.

I mean, historically mathematics have had areas full of "HACK:" comments, too--ones retroactively applied to the whole of Newtonian physics, even, but it's still useful enough that we keep it around!

Newtonian physics is not "a hack". It yields very precise results for simple gravitational interactions, at least up to the point where relativistic effects begin to dominate. Even Einstein's equations are not 100% "perfect". All mathematical models have their limitations. (Although some do produce better approximations than others.)

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#115

Post by eropple »

af3d wrote: post #114
eropple wrote: post #112

Earlier quoted context omitted.

I mean, historically mathematics have had areas full of "HACK:" comments, too--ones retroactively applied to the whole of Newtonian physics, even, but it's still useful enough that we keep it around!

Newtonian physics is not "a hack". It yields very precise results for simple gravitational interactions, at least up to the point where relativistic effects begin to dominate. Even Einstein's equations are not 100% "perfect". All mathematical models have their limitations. (Although some do produce better approximations than others.)

A hack is in the eye of the beholder, and many hacks are load-bearing and totally fine for the entire timespan for which the thing they're stashed within is expected to be useful. I agree with you that all mathematical models have their limitations--but the choice to use a good-enough one is, over sufficient time and distance, a tradeoff that can be described as such.

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#116

Post by madhadron »

xg15 wrote: post #99
FormerBandmate wrote: post #15

The top answer at the link explains it best: Good observation! The 3' poly(A) tail is actually a very common feature of positive-strand RNA viruses, including coronaviruses and picornaviruses. For coronaviruses in particular, we know that the poly(A) tail is required for replication, functioning in conjunction with the 3' untranslated region (UTR) as a cis-acting signal for negative strand synthesis and attachment to…

As a coder, I find it a bit frustrating how often explanations in biology contain fuzzy phrases like "plays a role in" or "is required for" or "works together with" or "modulates the activity of" - without ever expected what role it plays, why it is required or how it works together. So props to them for going a bit more into detail here - and also highlighting that the reason for the fuzzy phrases can often be that…

The other side of this is: what constitutes an explanation? What formal structure that you express observations in seems like knowing what's going on to you? Formal structures in fields tend to be matched to what the experimental abilities of the field are.

In programming, we designed our systems to give us what seem like hard bottoms in our formal models. Most programmers don't reason below the level of their structured programming language. Of the ones that do, most treat the processor instructions as a hard bottom. There are layers down and down until you have physicists working on semiconductor properties, but we have intentionally designed the layers so that you can comfortably rest on them.

In biology any formal structure you think in is logically poised over the abyss. What pins it in place is not that it is on philosophical bedrock, but the observations and experiments that the formal structure summarizes.

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#117

Post by farkanoid »

jkingsman wrote: post #48

If this sort of question fascinates you, you might like "Reverse Engineering the source code of the BioNTech/Pfizer SARS-CoV-2 Vaccine"[0], an article written with a tone that I've found to resonate with engineers and like-minded folk. [0] https://berthub.eu/articles/posts/reverse-engineering-source...

What a fascinating article! Thanks for sharing.

I didn't realise there was so much crossover between embedded design and biology!

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#118

Post by a_w »

jkingsman wrote: post #48

If this sort of question fascinates you, you might like "Reverse Engineering the source code of the BioNTech/Pfizer SARS-CoV-2 Vaccine"[0], an article written with a tone that I've found to resonate with engineers and like-minded folk. [0] https://berthub.eu/articles/posts/reverse-engineering-source...

https://news.ycombinator.com/item?id=25598270

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#119

Post by digitaltrees »

samus wrote: post #111
userbinator wrote: post #91

Earlier quoted context omitted.

Looks almost like a hex editor.

It kind of is. We are not quite advanced enough to have the equivalent of true programming languages for genetics.

But we will. GitHub for genetics would be awesome

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#120

Post by subroutine »

kevviiinn wrote: post #102
subroutine wrote: post #70

Earlier quoted context omitted.

The number of adenine repeats that confer functional properties is quite variable but it definitely needs to be more than "just 1". I've seen anywhere from 25-250 used in designed plasmids. The exact number people use in their engineered sequence is based on a number of factors, not all of them scientific in nature (e.g. companies charge per basepair synthesize a bespoke polypeptide; e.g. you copied the sequence from…

Iirc there's a protein that adds 12-15 slowly then another protein comes in and adds another 200+ when it detects the start of the tail. Not sure about the details about how or why it stops tho. At least when considering mRNA getting prepped for nuclear export

You are probably right, I'm not an expert on this process. But there's likely a difference between the innate eukaryotic cell polyadenylation process vs. how coronavirus accomplishes polyadenylation because coronavirus rna never enters the nucleus.
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