13.2 : Genome Copying Errors

Every time a human cell divides, the DNA polymerase enzymes copy over 3 billion base pairs with high fidelity, to be passed on to the daughter cells.

However, due to the sheer volume of information being duplicated, the DNA polymerase sometimes makes errors while copying. For example, an incorrect base may be added to the newly synthesized strand, such as a cytosine instead of thymine.

In some cases, such changes can be harmful, like the single nucleotide change from GAG  to GTG in the beta-hemoglobin gene which causes sickle-shaped red blood cells. This reduces the oxygen-carrying capacity of red blood cells, resulting in sickle cell anemia.

Extra bases may also be added or deleted from the genes. Such mutations are collectively called indels. In cystic fibrosis, a single base added or deleted in the CFTR gene can shift the reading frame such that the gene encodes a defective protein. This protein cannot transport chloride ions out of the lung epithelial cells, resulting in the accumulation of thick, glue-like mucus, which increases the risk of lung infection.

Fortunately, such copying errors occur at low frequency - around 1 error per 100,000 bases.

Additionally, the majority of these errors are rectified during the replication by DNA polymerase enzymes' proofreading activity before they can be passed to the daughter cells, or are fixed after replication by DNA repair enzymes. Nevertheless, in rare cases, errors may escape the repair process and pass on to the next generation.

However, not all mutations are harmful to the organism; most mutations are neutral, and some may confer survival advantages.

Antibiotic resistance is one beneficial trait that can arise via mutation.

For example, the antibiotic fluoroquinolone binds to a bacterial enzyme called DNA gyrase, and inhibits bacterial growth. However, when the genes coding for the enzyme DNA gyrase accumulate random base substitutions, this results in a mutated version of the enzyme. The antibiotic can no longer bind to this mutated enzyme, which leads to the survival and growth of bacteria, even in the presence of antibiotics.