Editing Selfish genetic element (section)

=== Gene-drive systems ===
The idea of spreading a gene into a population as a means of population control is actually quite old, and models for the dynamics of introduced compound chromosomes date back to the 1970s.<ref>{{cite journal | vauthors = Fitz-Earle M, Holm DG, Suzuki DT | title = Genetic control of insect population. I. Cage studies of chromosome replacement by compound autosomes in Drosophila melanogaster | journal = Genetics | volume = 74 | issue = 3 | pages = 461–75 | date = July 1973 | doi = 10.1093/genetics/74.3.461 | pmid = 4200686 | pmc = 1212962 }}</ref> Subsequently, the population genetics theory for homing endonucleases and CRISPR-based gene drives has become much more advanced.<ref name=":15" /><ref name=":28">{{cite journal | vauthors = Deredec A, Burt A, Godfray HC | title = The population genetics of using homing endonuclease genes in vector and pest management | journal = Genetics | volume = 179 | issue = 4 | pages = 2013–26 | date = August 2008 | pmid = 18660532 | pmc = 2516076 | doi = 10.1534/genetics.108.089037 }}</ref> An important component of modeling these processes in natural populations is to consider the genetic response in the target population. For one thing, any natural population will harbor standing genetic variation, and that variation might well include polymorphism in the sequences homologous to the guide RNAs, or the homology arms that are meant to direct the repair. In addition, different hosts and different constructs may have quite different rates of non-homologous end joining, the form of repair that results in broken or resistant alleles that no longer spread. Full accommodation of the host factors presents considerable challenge for getting a gene drive construct to go to fixation, and Unckless and colleagues<ref>{{cite journal | vauthors = Unckless RL, Clark AG, Messer PW | title = Evolution of Resistance Against CRISPR/Cas9 Gene Drive | journal = Genetics | volume = 205 | issue = 2 | pages = 827–841 | date = February 2017 | pmid = 27941126 | pmc = 5289854 | doi = 10.1534/genetics.116.197285}}</ref> show that in fact the current constructs are quite far from being able to attain even moderate frequencies in natural populations. This is another excellent example showing that just because an element appears to have a strong selfish transmission advantage, whether it can successfully spread may depend on subtle configurations of other parameters in the population.<ref name=":28" />