Gene Drive: The What, How, Why, and Whether We Should
Gene Drive: The What, How, Why, and Whether We Should
Tags: CRISPR, Gene drive synthetic, Replicator/site directed nucleaseN. Pazhayam, The Pipettepen, 2020.
Sexually reproducing organisms have two copies of most genes – one on the chromosome from the male parent, and one on the chromosome from the female parent. Genes also have alternative forms (called alleles) that are found at the same place on either chromosome, but can produce different phenotypic outcomes. An individual that has two chromosomes with the same allele is said to be homozygous for it, while an individual that has two chromosomes with different alleles is said to be heterozygous for it. Under regular Mendelian inheritance, the probability of inheriting a particular allele from a heterozygous parent is 50% – this is because offspring can only inherit one or the other chromosome from each parent. However, gene drive is a technology that changes this probability and makes it much higher than 50%. Theoretically, gene drive makes it possible to have a certain allele be inherited 100% of the time!
How does this work? Well, one of the most powerful gene drive mechanisms involves the use of the CRISPR/Cas9 system. In the germline of an organism heterozygous for the drive allele (the allele that we are trying to propagate through the population), Cas9, a protein that can cut DNA, creates a double strand break (DSB) on the chromosome that doesn’t have it. This prompts the cell to repair the DSB by copying in the drive allele from the homologous chromosome, leading to the cell becoming homozygous for the drive. Every meiotic product – or gamete – produced will now have this allele, ensuring that it is passed onto every offspring!