Gene drives – cheating evolution

Abstract

Kod organizama sa spolnim razmnožavanjem i s po dvije kopije svakog kromosoma, svaki alel bilo kojeg gena ima 50% šanse da se prenese na potomstvo (jer svaka gameta prima po jedan alel). Gene drives (hrv. gensko upravljanje) su sebični genetički elementi koji zaobilaze Mendelova pravila nasljeđivanja, pa njihovi aleli imaju šansu prijenosa na potomstvo veću od 50%. U zadnjih nekoliko godina, prirodno prisutni gene drive sustavi u različitim organizmima poslužili su kao inspiracija za dizajniranje sintetskih gene drive sustava u svrhu genetskog modificiranja populacija, a nakon otkrića tehnologije CRISPR-Cas9 ideja je doživjela veliki napredak. Aktualna istraživanja bave se mogućnostima primjene sintetskih gene drive sustava za suzbijanje malarije modifikacijom populacije komarca Anopheles stephensi i supresijom populacije komarca Anopheles gambiae, te za kontrolu populacija glodavaca. Neka od ograničenja uporabe sintetskih gene drive sustava su razvoj rezistencije na gene drive alele, potencijalni nepredvidljivi učinci, nekontrolirano širenje i zlouporaba. Da bi sintetski gene drive sustavi jednog dana mogli funkcionirati u divljim populacijama, istražuju se i mogućnosti supresije razvoja alela rezistentnih na gene drive te načini bolje kontrole širenja gene drive alela radi smanjenja negativnog utjecaja na neciljane vrste.In sexually reproducing organisms, with two copies of every chromosome, each allele of a particular gene has a 50% chance of being passed to progeny - because every gamete receives one of the alleles. Gene drives are selfish genetic elements that surpass the Mendelian laws of inheritance, so that the progeny has a chance greater than 50% to receive the gene drive allele. In the recent years, naturally occurring gene drive systems have inspired biologists to create synthetic gene drive systems that could be used as tools for genetic modification of entire populations. With the help of CRISPR-Cas9 technology, the idea has faced greater improvement. Current research focuses on using synthetic gene drive systems for malaria suppression either by modifying Anopheles stephensi mosquito population or suppressing Anopheles gambiae population, as well as for the population control of rodents. Potential limitations of using synthetic gene drive systems are development of alleles resistant to gene drive, unforseen effects, uncontrolled propagation and malpractice. For the synthetic gene drive systems to work in wild populations in the future, the methods for resistant allele suppression and for lowering the unwanted effects by better confinement to target species need to be further investigated