Editing Mutation (section)

==== Experiment in bacteria ====
Lunzer et al.<ref>{{Cite journal |last1=Lunzer |first1=Mark |last2=Golding |first2=G. Brian |last3=Dean |first3=Antony M. |date=21 October 2010 |title=Pervasive Cryptic Epistasis in Molecular Evolution |journal=PLOS Genetics |language=en |volume=6 |issue=10 |pages=e1001162 |doi=10.1371/journal.pgen.1001162 |issn=1553-7404 |pmc=2958800 |pmid=20975933 |doi-access=free }}</ref> tested the outcome of swapping divergent amino acids between two orthologous proteins of isopropymalate dehydrogenase (IMDH). They substituted 168 amino acids in ''Escherichia coli'' IMDH that are wild type residues in IMDH ''Pseudomonas aeruginosa''. They found that over one third of these substitutions compromised IMDH enzymatic activity in the ''Escherichia coli'' genetic background. This demonstrated that identical amino acid states can result in different phenotypic states depending on the genetic background. Corrigan et al. 2011 demonstrated how ''Staphylococcus aureus'' was able to grow normally without the presence of lipoteichoic acid due to compensatory mutations.<ref name="Corrigan-2011">{{Cite journal |last1=Corrigan |first1=Rebecca M. |last2=Abbott |first2=James C. |last3=Burhenne |first3=Heike |last4=Kaever |first4=Volkhard |last5=Gründling |first5=Angelika |date=1 September 2011 |title=c-di-AMP Is a New Second Messenger in Staphylococcus aureus with a Role in Controlling Cell Size and Envelope Stress |journal=PLOS Pathogens |volume=7 |issue=9 |pages=e1002217 |doi=10.1371/journal.ppat.1002217 |issn=1553-7366 |pmc=3164647 |pmid=21909268 |doi-access=free }}</ref> Whole genome sequencing results revealed that when Cyclic-di-AMP phosphodiesterase (GdpP) was disrupted in this bacterium, it compensated for the disappearance of the cell wall polymer, resulting in normal cell growth.<ref name="Corrigan-2011" />

Research has shown that bacteria can gain drug resistance through compensatory mutations that do not impede or having little effect on fitness.<ref name="Comas-2012">{{Cite journal |last1=Comas |first1=Iñaki |last2=Borrell |first2=Sonia |last3=Roetzer |first3=Andreas |last4=Rose |first4=Graham |last5=Malla |first5=Bijaya |last6=Kato-Maeda |first6=Midori |last7=Galagan |first7=James |last8=Niemann |first8=Stefan |last9=Gagneux |first9=Sebastien |date=January 2012 |title=Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes |journal=Nature Genetics |language=en |volume=44 |issue=1 |pages=106–110 |doi=10.1038/ng.1038 |pmid=22179134 |pmc=3246538 |issn=1546-1718}}</ref> Previous research from Gagneux et al. 2006 has found that laboratory grown ''Mycobacterium tuberculosis'' strains with rifampicin resistance have reduced fitness, however drug resistant clinical strains of this pathogenic bacteria do not have reduced fitness.<ref name="Gagneux-2006">{{Cite journal |last1=Gagneux |first1=Sebastien |last2=Long |first2=Clara Davis |last3=Small |first3=Peter M. |last4=Van |first4=Tran |last5=Schoolnik |first5=Gary K. |last6=Bohannan |first6=Brendan J. M. |date=30 June 2006 |title=The competitive cost of antibiotic resistance in Mycobacterium tuberculosis |url=https://pubmed.ncbi.nlm.nih.gov/16809538/ |journal=Science |volume=312 |issue=5782 |pages=1944–1946 |doi=10.1126/science.1124410 |issn=1095-9203 |pmid=16809538|bibcode=2006Sci...312.1944G |s2cid=7454895 }}</ref> Comas et al. 2012 used whole genome comparisons between clinical strains and lab derived mutants to determine the role and contribution of compensatory mutations in drug resistance to rifampicin.<ref name="Comas-2012" /> Genome analysis reveal rifampicin resistant strains have a mutation in rpoA and rpoC.<ref name="Comas-2012" /> A similar study investigated the bacterial fitness associated with compensatory mutations in rifampin resistant ''Escherichia coli''.<ref name="Reynolds-2000">{{Cite journal |last=Reynolds |first=M. G. |date=December 2000 |title=Compensatory evolution in rifampin-resistant Escherichia coli |journal=Genetics |volume=156 |issue=4 |pages=1471–1481 |doi=10.1093/genetics/156.4.1471 |issn=0016-6731 |pmc=1461348 |pmid=11102350}}</ref> Results obtained from this study demonstrate that drug resistance is linked to bacterial fitness as higher fitness costs are linked to greater transcription errors.<ref name="Reynolds-2000" />