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Neutral Mutations

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Neutral Mutations

The combination of the words "neutral" and "mutations" may seem like an error or fallacy. How can something be mutated - altered at the genetic level - and its effects be neutral? Well, not only are neutral mutations not a fallacy, they are quite common, representing the most commonly occurring forms of mutations. The relatively resilient nature of the genetic material of both us, as humans, and the many forms of life around us, makes this possible. It's important to understand the forms that neutral mutations can come in, and how these are exhibited at both the genetic level and in the lives of varied organisms.

Neutral mutation - definition

A neutral mutation is defined as any mutation that occurs within an organism's genome, that either has no effect at all, or has an effect that is neither better nor worse than the effect that the natural, wild-type gene would confer.

We can see from this definition that, under the category of neutral mutations, there is a subcategory. That is, if neutral mutations can be drawn as one big Venn diagram, encased in the circle representing them are another type of mutation (Fig. 1). These are called silent mutations, and they are the mutations with no effect at all on the organism.

All silent mutations are neutral mutations, but not all neutral mutations are silent mutations.

Neutral mutations neutral vs silent mutations studysmarter originalFig. 1: Neutral vs silent mutations. Studysmarter original.

In summary, neutral mutations neither increase nor decrease the fitness - that is, the capacity of an organism to produce live offspring - of an organism, nor alter its survivability, nor confer upon it any competitive advantage nor disadvantage.

Neutral mutations may change some things about an organism, such as the amino acid that is exhibited at a certain spot in a certain protein, but these changes made are neutral - they don't affect the above factors.

Silent mutations, quite literally change nothing about the way an organism presents itself, even in terms of the amino acids that make up its proteins. Silent mutations are silent in their effect - presumably, the only way to know they are occurring or have occurred is to look at the genes.

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 (in humans, after copying about 100 - 1000 nucleotides, DNA polymerase tends to have at least one error, where an incorrect nucleotide (adenosine, cytosine, thymine, or guanine) is planted in the place of another). 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.

Mutagen - an agent that predisposes to (or directly causes) genetic mutations. X-rays are an example of mutagens.

It may seem to be a rather small-scale concern, that of neutral mutations leading to amino acid changes. However, we must not underestimate what these proteins can be - proteins decide everything from the skin, eye, and hair color of humans and animals; to plant flower colors and seed shapes, to bacterial antibiotic resistance and infectivity, to ion channels, receptors, and organelles at the cellular level; and so much more. Essentially the proteins exhibited by living organisms decide, to a very large extent, how they look, act, interact, survive, and reproduce.

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 (Fig. 2). Three sequential nucleotides together are termed a codon.

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.

Neutral mutations missense researchgateFig. 2: Missense. Researchgate.

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 (Fig. 3). 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.

Neutral mutations nonsense the biology notesFig. 3: Nonsense. The Biology Notes.

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. For example, if two nucleotides are added; this leads to a frameshift mutation. If one nucleotide is deleted, this leads to a frameshift mutation, and so on. Frameshift mutations often lead to a series of missense mutations, or a nonsense mutation (Fig. 4).

Neutral mutations frameshift mutation socraticFig. 4: Frameshift mutation. Socratic.

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 mutations early on, depicting how all silent mutations are neutral mutations, but not all neutral mutations are silent mutations. (Most often neutral mutations are missense mutations that do not affect the overall protein activity or structure.)

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.

Amino acids have two to five codons that encode their translation. For example, the amino acid proline is translated when any of the following codons: CCT, CCC, CCA, and CCG, are read. Glutamate is translated from from two possible codons - GAA and GAG.

neutral mutations silent researchgateFig. 5: Silent. Researchgate.

Neutral mutation rate

Neutral mutations occur at higher rates than the two other main forms of mutations - beneficial mutations and deleterious (harmful) mutations. Natural selection should theoretically, not play a factor in the inheritance of neutral mutations because they neither confer fitness - and hence would be selected for in a population, nor reduce fitness - and hence would be selected against.

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

  • 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.

Here is the codon table (Fig. 6).

neFig. 6: codon table. toppr.

Remember that U (uracil) is to RNA what T (thymine) is to DNA!

Q: What form of mutation occurs when this code:

ATGGTGCACCTGACTCCT
is improperly replicated as this code:
ATGGTGCAACTGACTCCT

A: A missense mutation. The original strand codes:

StartValHisLeuThrPro
and the mutant strand codes:
StartValGlnLeuThrPro

While this could be a neutral mutation, potentially, it could not be a silent mutation.

Q: What form of mutation occurs when this code:

ATGCTTATAGCGGCGGGT

is improperly replicated as this code:

ATGCTTATCGCGGCGGGT

A: A missense mutation. The original strand codes:

StartLeuIleAlaAlaGly

and the mutant strand codes:

StartLeuIleAlaAlaGly

The amino acid sequence did not change, even though the DNA sequence did, thus this is a silent mutation.

Neutral Mutations - Key takeaways

  • Neutral mutations are more common than both beneficial and deleterious mutations
  • Neutral mutations are theoretically not selected for or against, although gene linkage can change this
  • Neutral mutations can be silent - which means there is no difference in the amino acid sequence although an alteration has occurred in the genetic code.
  • Silent mutations are due to the degeneracy or redundancy of the genetic code.
  • Neutral mutations are often missense mutations, but can rarely be nonsense or frameshift mutations as well.

Frequently Asked Questions about Neutral Mutations

A mutation that neither helps nor harms an organisms survivability and fitness

brown colored fly coat vs wild-type light tan.

they help to explain genetic drift occurrences over generations.

Silent mutations are a type of mutation with neutral effect

If it either doesn't alter the protein or does alter it in such a way that it has no effect on protein structure or function.

Final Neutral Mutations Quiz

Question

What larger group of mutations do silent mutations fit into?

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Answer

Neutral mutations

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Question

Fill in the blanks: _____ silent mutations are neutral mutations, _____ all neutral mutations are silent mutations.

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Answer

All, but not

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A silent mutation is one in which the ______ is unchanged

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Answer

Amino acid sequence

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Question

Most mutations are

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Answer

neutral

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Question

Additions or deletions of amino acid codons in multiples of ____ are required in order to not have a frameshift mutation

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Answer

3

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Question

What causes neutral mutations to be selected for or against? 

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Answer

If they exhibit gene linkage to a relevant gene that increases or decreases fitness.

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Question

How many stop codons are there?

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Answer

Three: UAA, UGA, UAG (or TAA, TGA, TAG if reading DNA).

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Question

What does it mean when we say the DNA code is degenerate

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Answer

It is dilapidated

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Question

What's another term for degeneracy in genetics?

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Answer

Redundancy

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Question

Nonsense mutations lead to a premature ____

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Answer

Stop codon

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Question

True or false: Frameshift mutations are typically neutral mutations

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Answer

False

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Question

True or False: If the alternate amino acid in a missense mutation has the same chemical properties as the original, it is more likely to be a neutral mutation

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Answer

True

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Question

What is the start codon

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Answer

ATG (or AUG in mRNA)

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Question

Examples of neutral mutations that differ between the species include:

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Answer

Human vs cow vs pig insulin

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Question

Which is more dangerous

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Answer

Frameshift mutation

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