Week 2 HW: DNA Read/Write/Edit

My homework

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 a polymerase is 1:10^6 error rate with a 3.2 billion nucleotide in the human genome. In biology, base pairing and proofreading/erro correction mechanisms and layers exist to minimize mutations inside the genome.

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?

Proteins are strings of amino acids, there are 20 typical amino acids encoded by codons of 3 nucleotides. The genetic material in mRNA is written in codons, a set of specific consecutive triplets of nucleotides. Because RNA contains four different bases (A, U, C, G), there are 4³ = 64 possible codons. These 64 codons are more than enough to specify the 20 amino acids, resulting in some redundancy (multiple codons can code for the same amino acid). Additionally, three special codons function as stop signals that mark the end of the protein sequence. Also That being said, there are an enormous number of possible DNA sequences that can encode the same average human protein due to redundancy in the genetic code. Since most amino acids are encoded by multiple codons, a ~400-amino-acid protein could theoretically be encoded by roughly 3^{400 (~10}190) different DNA sequences. However, in practice, many of these sequences do not work well because synonymous codons affect translation efficiency, mRNA stability and structure, splicing, protein folding, and overall gene expression. So while the amino acid sequence may be the same, the cellular outcome can differ significantly.

Why is it difficult to make oligos longer than 200nt via direct synthesis? Why can’t you make a 2000bp gene via direct oligo synthesis?

Since oligo synthesis is done by chemical synthesis, bases are added one at a time, increasing the number of errors thus as teh fragment size increases. Thus uligos longer than ~200 nt are difficult because each nucleotide addition has a small error rate, so errors accumulate with length—making direct synthesis of something like a 2000 bp gene impractical due to low yield and high mutation frequency.

Choose ONE of the following three questions to answer; and please cite AI prompts or paper citations used, if any.

[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”?

Until now, essential amino acids (EAAs) are defined as AAs whose carbon skeletons are insufficiently or not synthesized in a de novo manner by animal cells relative to metabolic needs. EAAs are Cysteine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophane, Tyrosine, and Valine. The lysine contingency is a description of an attempt to control the uncontrollable. A researcher genetically edited organisms to make them lysine deficient, the idea behind it as a security to control animals. If the latter weren’t supplied with this specific amino acid they would cease to exist. However, this in reality doesn’t matter as these animals can be able to find food sources rich in lysine and survive.

[Given slides #2 & 4 (AA:NA and NA:NA codes)] What code would you suggest for AA:AA interactions? •
[(Advanced students)] Given the one paragraph abstracts for these real 2026 grant programs sketch a response to one of them or devise one of your own: https://arpa-h.gov/explore-funding/programs/boss https://www.darpa.mil/research/programs/smart-rbc https://www.darpa.mil/research/programs/go