When the cell of any living thing is preparing for division, DNA replication starts with the help of many enzymes. First, the DNA double helix is unwound and separated by topoisomerase and helicase, respectively. Each strand then serves as a template for DNA polymerase to synthetize a new, complementary strand (i.e. in the DNA, adenine (A) always pairs with thymine (T), and guanine (G) always pairs with cytosine (C)). Note that instead of north, south, east, and west, the DNA has its direction recognized by a 5’ → 3’ system; the enzyme DNA polymerase can only synthesize DNA from 5’ to 3’ direction.
When DNA is replicated, errors can occur, but they are extremely rare. The initial error rate of DNA polymerase is about 1 mistake per 100,000 nucleotides synthesized. However, cells are equipped with proofreading and mismatch-repair systems that correct almost all of these errors. After these correction mechanisms act, the real error rate drops to about 1 in 10,000,000,000 (ten billion) nucleotides. To put this into perspective, let’s consider Arabidopsis thaliana, a common model plant. Its genome contains approximately 2.7 million nucleotides per cell. With the corrected mutation rate, you would expect one mutation to occur for every:
In other words, a single mutation in Arabidopsis typically appears only after thousands of replication cycles.
The first time that the replication is checked for errors is by DNA polymerase itself, which discriminates against the incorporation of mismatched bases. Proofreading, also made by DNA polymerase, is another important mechanism for correction of errors in DNA replication. After finishing the replication of each strand, DNA polymerase goes through the complementary strand again to check for any errors. Even with all that scheme to repair mistakes if they happen, there is still a chance that an error goes through.
Now we understand that mistakes, or so-called mutations, can happen naturally. But how do they affect an organism? ↓