Bits&Bio Log Week 2/3: Artificial Chromosomes and Adaptive Dissipation (Retroactive Post)

Artificial Chromosomes

Resources

Artificial Chromosomes: Ideal Vectors?

One of the referred papers, about mini chromosomes created by using telomeres to direct breakage of a Y chromosome

Another (MUCH MORE RECENT) article on Human Artificial Chromosomes (HAC)

wikipedia page for HAC

Vocab: selectable marker gene (like the one in the paper is for anti-biotic resistance), cis-/trans-acting, spheroplast transformation, alphoid DNA, transfection, cytogenic characterization, acrocentric DNA, episome, inverted meiosis, recombinase, heterochromatin, kinetochore, centromeric chromatin

Questions

Have we created artificial sites in DNA that make adding/turning off modules of our own genome easier to do?

Why does the circular DNA turn into a linear molecule in the Yeast, and is that why you have the “palindromic telomeres”, as a site for the splitting, so they become the ends of the linear molecule?

“two telomeric sequences was assembled in Escherichia coli and introduced into S. cerevisiae by spheroplast transformation. After transformation, the telomeric sequences resolved to yield a linear derivative of the starting plasmid.”

Are they only “retained…for at least 20 generations” because of rapid recombination, selection, etc?

What do they mean by specific origins of replication as one of the cis-acting DNA sequences necessary for a properly functioning mammalian chromosome.

“Centromeres pose significant problems to the construction of mammalian artificial chromosomes for two reasons: (1) the DNA sequences required for centromere function are poorly defined and (2) the sequences that have been shown to confer centromere function are difficult to manipulate.” — Why and why?

Mammalian chromosomes are much larger than what can be manipulated by cloning systems — is that only biological cloning systems or “DNA Printers”?

How do you print DNA in a lab?

What kinds of manipulations or IO can be directed at a single cell granularity?

What does it mean for “human or mouse genomic DNA to act as a carrier”?

What is the reason to separate DNA into chromosomes, and how is that separation used? What comes to mind is non-allelic genes that interact with the same phenotypic response. Although, like the fly eye-color example in Voet, isn’t that only up to the granularity of phenotype, like the eye color? That isn’t a description of whether those non-allelic genes are modifying the same underlying mechanism — it may be like a manual override behavior right?

For anti-viral/bacterial therapies, could we introduce some DNA which clobbers others when it comes time for replication? Even more insidiously, could it exist for x generations and then clobber, so it might spread laterally for bacteria?

Like physics has sub-domains based on the types of mechanism or environmental regimes being studied, what are the corresponding domains for biology: biochemistry (mechanical and electrical engineering), anatomy (geography), endocrinology and neuroscience (networking, control, and information theory)

Could we make branching encodings of the polypeptides with branches switched based on environmental factors? Could we expand the regulatory sequences of DNA to make a “branched” equivalent?

Adaptive Dissipation

Resources

https://en.wikipedia.org/wiki/Amino_acid

https://en.wikipedia.org/wiki/Alpha_and_beta_carbon

https://en.wikipedia.org/wiki/Fundamental_thermodynamic_relation

https://en.wikipedia.org/wiki/Boltzmann_distribution

https://en.wikipedia.org/wiki/Second_law_of_thermodynamics

https://en.wikipedia.org/wiki/Onsager_reciprocal_relations

Voet and Voet, 4th edition of Biochemistry

Jeremy England Article on adaptive dissipation

Questions

How is entropy density defined?

Does England’s article rely on the constant volume assumption of Onsager?

What is the derivation of equation 4 in his paper?

Why is there a separate probability distribution for the time-reversed trajectory?

How is this different from simply observing that low-entropy states can be lower-energy states too? Otherwise, wouldn’t it even be a problem for chemical bonds to form? That introduces new structure, reducing the number of reconfigurations of the system that result in the same overall state variables.

Answers

The idea is that between two trajectories for system evolution that have the same likelihood to revert to the original state, the one that dissapates the more energy by doing work on its surroundings is likely to occur. Given two states with the final energy, the one that does more work on the surroundings is also less likely to be reversed. The critical part is that this holds even when arbitrary time-varying fields drive the system evolution. That means we can drive a system into some low-entropy state by injecting energy, but if that new structure also dissipated enough of the energy we put into the system, it is unlikely to revert to a high-entropy state.

Science, Society, and Startups | Stanford ‘22