Week 2 pre HW: DNA Read, Write and Edit

Homework Questions from 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? Ans: DNA polymerase has an inherent error rate of approximately 1 in 10⁶ bases. Given the human genome size of about 3.2 billion base pairs, this would lead to thousands of mutations each time a cell divides if left uncorrected. To maintain genomic stability, cells use a multi-layered error-correction system. First, DNA polymerase performs immediate proofreading through its exonuclease activity. This is followed by post-replication mismatch repair (MMR) mechanisms. Together, these processes greatly enhance replication accuracy, reducing the final error rate to roughly 1 in 10⁹–10¹⁰, meaning fewer than one error typically occurs per genome duplication.

  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? Ans: An average human protein (~1036 bp) can be coded by many synonymous codons because the genetic code is redundant.In practice, many of these codes fail because they can create secondary structures that block translation, contain sequences that trigger RNA cleavage, or use “rare” codons that the host cell cannot efficiently process.

Homework Questions from Dr. LeProust:

  1. What’s the most commonly used method for oligo synthesis currently? Ans: The phosphoramidite method is currently the most widely used chemistry for oligonucleotide synthesis. It involves a four-step cyclic process: coupling, capping, oxidation, and deblocking—to add nucleotides one by one onto a solid support, such as Controlled Pore Glass (CPG) or silicon chips.

  2. Why is it difficult to make oligos longer than 200nt via direct synthesis? Ans: Oligonucleotide synthesis occurs by adding one nucleotide at a time, and each step has a small probability of error. As the length increases, these errors accumulate, reducing the yield of correct full-length oligos. In addition, longer oligos are more prone to incomplete reactions and strand loss during synthesis.

  3. Why can’t you make a 2000bp gene via direct oligo synthesis? Ans: Directly synthesizing a 2000 bp gene is not feasible in practice. Errors accumulate with each step, resulting in low yield and incorrect sequences. Hence, long genes are constructed by assembling shorter, accurately synthesized oligos and then applying error-correction methods.

Homework Question from George Church: The question choosed by me

  1. [Using Google & Prof. Church’s slide #4] What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”? Ans: Essential amino acids in animals (10):

Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine, and Arginine . These amino acids cannot be synthesized by animals and must be obtained from the diet

Lysine contingency : Lysine contingency refers to the idea that animal life is fundamentally dependent on external sources of lysine because animals cannot synthesize it themselves. Since lysine is an essential amino acid and often scarce in plant-based foods, growth and survival become contingent on its availability. This makes lysine a key metabolic bottleneck shaping nutrition, agriculture, and evolutionary constraints.

My views The fact that lysine is an essential amino acid for all animals reinforces the idea of the lysine contingency—that animal life is inherently dependent on external biological systems (plants, microbes, or other animals) to supply lysine.We are all metabolically fasten to the external world, relying on a constant “supply chain” of plants and microbes to build our bodies.

Even when we think about survival in extreme environments, like a colony on Mars. Instead of trying to “fix” human genetics to make us self-sufficient which is ethically messy and biologically complex it makes far more sense to master the environment around us. By engineering hardy, high-yield, lysine-producing plants or yeast, we solve the survival puzzle without ever touching a human strand of DNA. It’s a strategy that’s not only safer and more flexible but one that respects our natural biology by simply ensuring the “bio-battery” we’ve always relied on never runs dry. At last the lysine contingency shows that human survival depends on food systems, not genetic independence. For extreme environments, engineering plants and microbes is a safer and smarter solution than changing human biology or animal biology.

Reference Jurassic Park Wiki. (n.d.). Lysine contingency. Fandom. Retrieved from https://jurassicpark.fandom.com/wiki/Lysine_contingency