Editing Silent mutation (section)

=== Primary structure ===
{{main|Biomolecular structure#Primary structure}}
A nonsynonymous mutation that occurs at the genomic or transcriptional levels is one that results in an alteration to the amino acid sequence in the protein product.  A protein's [[primary structure]] refers to its amino acid sequence.  A substitution of one amino acid for another can impair protein function and tertiary structure, however its effects may be minimal or tolerated depending on how closely the properties of the amino acids involved in the swap correlate.<ref name="pmid19289044">{{cite journal | vauthors = Teng S, Madej T, Panchenko A, Alexov E | title = Modeling effects of human single nucleotide polymorphisms on protein-protein interactions | journal = Biophysical Journal | volume = 96 | issue = 6 | pages = 2178–88 | date = March 2009 | pmid = 19289044 | pmc = 2717281 | doi = 10.1016/j.bpj.2008.12.3904 | bibcode = 2009BpJ....96.2178T }}</ref>  The premature insertion of a [[stop codon]], a [[nonsense mutation]], can alter the primary structure of a protein.<ref name="pmid21089233">{{cite book |last1=Strachan |first1=Tom |last2=Read |first2=Andrew P. |name-list-style=vanc |title=Human Molecular Genetics |publisher=Wiley-Liss |edition=2nd |isbn=978-1-85996-202-2 |id=NBK7580 |year=1999 |pmid=21089233 |url=https://archive.org/details/humanmolecularge0002stra |url-access=registration }}</ref>  In this case, a truncated protein is produced.  Protein function and folding is dependent on the position in which the stop codon was inserted and the amount and composition of the sequence lost.

Conversely, silent mutations are mutations in which the amino acid sequence is not altered.<ref name="pmid21089233"/> Silent mutations lead to a change of one of the letters in the triplet code that represents a [[codon]], but despite the single base change, the amino acid that is coded for remains unchanged or similar in biochemical properties.  This is permitted by the [[degeneracy of the genetic code]].

Historically, silent mutations were thought to be of little to no significance.  However, recent research suggests that such alterations to the triplet code do affect protein translation efficiency and protein folding and function.<ref name="pmid20617253">{{cite journal | vauthors = Czech A, Fedyunin I, Zhang G, Ignatova Z | title = Silent mutations in sight: co-variations in tRNA abundance as a key to unravel consequences of silent mutations | journal = Molecular BioSystems | volume = 6 | issue = 10 | pages = 1767–72 | date = October 2010 | pmid = 20617253 | doi = 10.1039/c004796c }}</ref><ref name="pmid17716239">{{cite journal | vauthors = Komar AA | title = Silent SNPs: impact on gene function and phenotype | journal = Pharmacogenomics | volume = 8 | issue = 8 | pages = 1075–80 | date = August 2007 | pmid = 17716239 | doi = 10.2217/14622416.8.8.1075 }}</ref>

Furthermore, a change in primary structure is critical because the fully folded tertiary structure of a protein is dependent upon the primary structure.&nbsp; The discovery was made throughout a series of experiments in the 1960s that discovered that reduced and denatured RNase in its unfolded form could refold into the native tertiary form.&nbsp; The tertiary structure of a protein is a fully folded polypeptide chain with all hydrophobic R-groups folded into the interior of the protein to maximize entropy with interactions between secondary structures such as beta sheets and alpha helixes.&nbsp; Since the structure of proteins determines its function, it is critical that a protein be folded correctly into its tertiary form so that the protein will function properly.&nbsp; However, it is important to note that polypeptide chains may differ vastly in primary structure, but be very similar in tertiary structure and protein function.<ref>{{Cite web|url=https://ocw.mit.edu/courses/biology/7-88j-protein-folding-and-human-disease-spring-2015/study-materials/MIT7_88JS15_Anfinsen.pdf|title=MIT Biochemistry Lecture Notes-Protein Folding and Human Disease}}</ref>