Pre-HW Week 2 From Professor Jacobson

My Homework

  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?

DNA polymerase, the enzyme that copies DNA, makes a mistake roughly once every 10⁴ to 10⁵ nucleotides synthesized, which sounds small but would lead to about 300,000 errors per round of human‑genome replication (about 3 billion bases) if left unchecked. Biology solves this by stacking multiple layers of quality control: the polymerase active site is selective for correct base pairs, the enzyme can proofread its own work by removing mispaired bases (3′→5′ exonuclease activity), and after replication specialized mismatch repair proteins scan and fix errors, bringing the effective mutation rate down to about 1 per 10⁷ to 10⁹ bases per cycle, which keeps the overall mutation load low enough for the organism to function reliably.

  1. 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?

An “average” human protein is roughly 300–400 amino acids long, and each amino acid is encoded by a DNA codon of 3 nucleotides, since the genetic code is degenerate (most amino acids have multiple codons), there are immensely many different DNA sequences that could encode the same amino‑acid sequence for such a protein on the order of many trillions or more of distinct nucleotide codes just for one average length protein. In practice, not all of these DNA variants actually work well because some change regulatory features (such as promoter or splice‑site signals), others introduce mRNA‑structure shifts that affect translation efficiency or trigger nonsense‑mediated decay, and still others create cryptic signals (like premature stop codons, frameshifts, or toxic repeat‑expansion‑like sequences) that either kill the protein’s function, destabilize the mRNA, or make the encoded protein harmful to the cell.