Week 2: Lecture Prep

Professor Jacobson

1. Nature’s machinery for copying DNA is called polymerase. What is the error rate of polymerase? How does this compare to the length of the human genome. How does biology deal with that discrepancy?

The error rate of polymerase is 1 error for every $10^6$ bases. In the human genome there are approximately 3.2 billion base pairs [1]. This means we expect on average 3,200 errors in every cell division. This is extraordinarily high at first glance. However, nature deals with this via an error correction system called the MutS repair system, which helps to repair these errors.

2. How many different ways are there to code (DNA nucleotide code) for an average human protein? In practice what are some of the reasons that all of these different codes don’t work to code for the protein of interest?

The average human protein is 1036 bp and on average each amino acid is coded by 3 possible DNA sequences [2]. So, for each amino acid sequence there are $3^{1036}$ possible distinct DNA sequences for a given protein. These are of course theoretical estimates, in practice DNA sequences that theoretically code for the same protein don’t behave exactly the same. They will have different GC content and therefore different levels of stability, which can affect the structure [3].

Dr. LeProust

1. What’s the most commonly used method for oligo synthesis currently?

Phosphoramidite chemistry

2. Why is it difficult to make oligos longer than 200nt via direct synthesis?

Looking at the DNA synthesis cycle shown in the slides, we add one base pair per iteration, that means if we assume some error rate at each iteration, the probability that you have an error at some point in the 200 cycles increases exponentially.

3. Why can’t you make a 2000bp gene via direct oligo synthesis?

Following my earlier argument if we want to create a 2000bp sequence, we are likely to have many errors. Therefore, it is likely that the gene we create will have enough errors to be non-functional.

Professor Church

What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”?

  • Histidine (His)
  • Isoleucine (Ile)
  • Leucine (Leu)
  • Lysine (Lys)
  • Methionine (Met)
  • Phenylalanine (Phe)
  • Threonine (Thr)
  • Tryptophan (Trp)
  • Valine (Val)
  • Arginine (Arg)

I am unsure if we are actually discussing the “Lysine contingency” from Jurassic Park, but I am going to assume we are. I don’t know enough about dinosaurs to say if they could or could not produce Lysine, but that’s not particularly important. This is an essential amino acid, meaning modern animals cannot produce it on their own, but modern animals are living. So, obviously there must exist food sources for both carnivores and herbivores to consume lysine. Therefore, a dinosaur would also be able to consume these sources (but perhaps they require more?) Anyway, I am doubtful of this logic. Or perhaps, I am a fan, because as a result of this logic I have control over all lions, tigers, and bears, oh my!

Citations:

[1] slide 24 [2] slide 6 [3] slid 39 [4] A Simple Guide to Phosphoramidite Chemistry and How it Fits in Twist Bioscience’s Commercial Engine: https://www.twistbioscience.com/blog/science/simple-guide-phosphoramidite-chemistry-and-how-it-fits-twist-biosciences-commercial

AI prompts

“What are the 10 essential amino acids in all animals”