A CRISPR-based gene drive is a synthetic genetic system designed to increase the inheritance probability of a specific allele beyond Mendelian expectations. This is achieved by encoding the CRISPR-Cas9 system within the genome such that, upon fertilization, the Cas9 enzyme cuts the homologous chromosome at a specific site. The host cell's DNA repair machinery then copies the drive allele into the cut site via homology-directed repair (HDR), resulting in a homozygous genotype for the gene drive.
In a sexually reproducing diploid population, a standard heterozygote (Aa) transmits allele A to 50% of offspring on average. However, a heterozygote carrying a fully efficient gene drive (A*) will convert the wild-type allele (a) to the gene drive allele (A*) in nearly all gametes, leading to inheritance rates approaching 100%.
However, gene drives can fail to spread if:
Consider a model of a large, randomly mating insect population with discrete generations, where the fitness (relative reproductive success) of genotypes is as follows:
| Genotype | Inheritance | Fitness |
|---|---|---|
| A*/A* | 100% A* | 0.7 |
| A*/a | 100% A* | 0.8 |
| a/a | 50% a | 1.0 |
Assume the gene drive is introduced into 1% of individuals, all of whom are heterozygotes (A*/a). Resistant alleles (a^r) are ignored for this model.
Which of the following best explains why the A* allele might fail to spread to fixation in this population, despite its biased inheritance?
A. The drive converts all heterozygotes to homozygotes, which reduces the total number of offspring produced.
B. Natural selection opposes the spread due to the lower reproductive success of individuals carrying the A* allele.
C. The drive’s mechanism is less efficient in homozygotes than in heterozygotes.
D. Inheritance bias is irrelevant in large, randomly mating populations.
What is the effective transmission rate of the A* allele from A*/a individuals, accounting for both inheritance and relative fitness?