Neutral Mutations

Neutral genetic mutations

Let us look at what is happening on the level of the genome when neutral mutations occur. Non-silent neutral mutations occur when some error in DNA replication leads to a change in the amino acid sequence that comprises a protein. This occurs when DNA polymerase causes this error, often due to its inherent fallibility as a copying machine

Errors in DNA polymerase replication can also occur because of mutagens present in the environment, that either alter the existing genetic code or interfere with the ability of DNA polymerase to properly replicate.

The errors in replication that lead to these non-normal, non-wild-type proteins; arise from alterations in amino acid coding sequences, which in turn arise from alterations in DNA sequences. These DNA alterations can be missense, nonsense, or frameshift, while silent mutations are distinguished by the fact that they alter DNA but do not alter amino acids or proteins.

Missense mutations

Missense mutations occur when the nucleotide (or nucleotides) that are altered or replaced lead to the production of different amino acids than were originally intended.

Each codon represents and eventually is translated into a single amino acid, and sometimes (but not always, this exception occurs in silent mutations) altering one of these nucleotides leads to an alternate amino acid.

While this can be very rarely beneficial, and sometimes deleterious, this is often neutral; especially if the two amino acids have similar properties (both acidic, both basic, both hydrophobic, etc.) and are not in a very important region of the protein such as the receptor where it makes interactions.

Nonsense mutations

Nonsense mutations are seen when an alteration in a strand of DNA leads to a premature STOP codon. Just as different combinations of three nucleotides can code for the translation of a specific amino acid; three specific codons encode a message that tells the ribosomes to STOP producing a certain protein. These three include - TGA, TAA, and TAG.

Nonsense mutations are most often deleterious because a premature stop leads to a truncated and often nonfunctional protein. Nonetheless, they can still be neutral, if the remainder of the amino acid sequence following the stop codon is very small and largely irrelevant.

Frameshift mutations

We noted that codons occur in threes, and the genetic code is read in these triplets. Thus, frameshift mutations occur when there are spontaneous additions or deletions of nucleotides in any amount that is not a multiple of three.

Frameshift mutations often lead to a series of missense mutations or nonsense mutations.

It's extremely rare for a frameshift mutation to be neutral. Like a nonsense mutation, this would most likely occur if the frameshift happened near the very end of an amino acid sequence, thus not altering the protein very much. Most often, frameshift mutations are deleterious.

Silent mutations

We distinguished this form of mutation early on, depicting how all silent mutations are neutral mutations, but not all neutral mutations are silent mutations.

When examining silent neutral mutations we come across a certain important feature of the genetic code. It is degenerate (redundant). In genetics, degeneracy means there are multiple codons (combinations of three nucleotides - A, C, G, and T) that can lead to the same amino acid.

Neutral mutation rate

Neutral mutations occur at higher rates than the two other main forms of mutations - beneficial mutations and deleterious (harmful) mutations.

Nonetheless, we have seen that although most mutations are neutral and have totally randomized chances of being inherited, many other neutral mutations are linked (sometimes called genetic hitchhiking) to other mutations that do have some effect, whether positive or negative. Thus, these neutral mutations will occur at the same rates (randomly) but may be more or less persistent in a population due to the effects of gene linkage and natural selection.

Neutral mutations in animals

Here we explore the various neutral mutations that can occur in animals such as pigs, flies and dogs.

• Speciation and differing proteins

  • Example: Insulin

  • Many different protein-based hormones (such as insulin) are found in both animals and human beings, especially mammals. This occurs to the extent that, animal versions of these hormones - such as pig insulin - has historically been given to humans who lack the proper amount of their own. Scientists hypothesize that certain neutral mutations occurred that led to the differences between human, bovine (that means cows), and pig-garnered insulin; which all demonstrate differences between species but are effectively the same and can be used as such.

• Fruit flies

  • Example: Coloration

  • Most fruit flies naturally have light tan bodies, however, there exist mutant phenotypes with brighter coloring; nearing yellow, or darker coloring; nearing black. These mutations do not appear to reduce or increase fitness, thus they are non-silent, non-neutral mutations.

• Dogs

  • Example: Size and appearance

  • Dogs have the broadest range of size of any mammal, and this is due to their inherent genetic capacity, and selection; typically by humans. Individual mutations that occur in a dog or dog family were consistently inbred to produce multiple dogs with a pronounced version of this feature (whether it be teacup size or corkscrew fur), which leads to the extreme degree of variation we see in pet dogs today.

Neutral mutation practice examples

We can work through a set of examples of neutral mutations to determine what specific designation they should be given - missense, nonsense, silent, or frameshift.