cubeClvR2: Inheritance Cube: 2-Locus ClvR (Cleave and Rescue)

In MGDrivE: Mosquito Gene Drive Explorer

Description

Based on the Cleave-and-Rescue system of Oberhofer, this is a 3-locus Cas9-based toxin-antidote system. The first locus carries the Cas9, the second locus carries the gRNAs, and a recoded copy of an essential gene. The third locus is the targeted essential gene. This gene can be completely haplosufficient (hSuf = 1) or completely haploinsufficient (hSuf = 0). It is assumed that having 2 copies of the gene (be it wild-type at the second locus or recoded at the first) confers complete viability. Additionally, loci 1 and 2 can be linked, given crM and crF, imitating the original 2-locus ClvR system. For this construct, the first locus will have 2 alleles, the second will have 2 alleles, and the third will have 3 alleles:

• Locus 1

  • W: Wild-type

  • C: Cas9

• Locus 2

  • W: Wild-type

  • G: gRNAs and recoded essential gene

• Locus 3

  • W: Wild-type

  • R: Functional resistant

  • B: Non-functional resistant

Usage

cubeClvR2(
  cF = 1,
  crF = 0,
  ccF = cF,
  ccrF = crF,
  cM = 1,
  crM = 0,
  ccM = cM,
  ccrM = crM,
  dW = 0,
  drW = 0,
  ddW = dW,
  ddrW = drW,
  hSuf = 1,
  crossF = 0.5,
  crossM = 0.5,
  eta = NULL,
  phi = NULL,
  omega = NULL,
  xiF = NULL,
  xiM = NULL,
  s = NULL
)

Arguments

cF	Female cutting rate, one ClvR allele
crF	Female functional resistance rate, one ClvR allele
ccF	Female cutting rate, two ClvR alleles
ccrF	Female functional resistance rate, two ClvR alleles
cM	Male cutting rate, one ClvR allele
crM	Male functional resistance rate, one ClvR allele
ccM	Male cutting rate, two ClvR alleles
ccrM	Male functional resistance rate, two ClvR alleles
dW	Female deposition cutting rate
drW	Female deposition functional resistance rate
ddW	Female deposition (HH) cutting rate
ddrW	Female deposition (HH) functional resistance rate
hSuf	Haplosufficiency level, default is completely sufficient
crossF	Crossover rate in females, 0 is completely linked, 0.5 is unlinked, 1.0 is complete divergence
crossM	Crossover rate in males, 0 is completely linked, 0.5 is unlinked, 1.0 is complete divergence
eta	Genotype-specific mating fitness
phi	Genotype-specific sex ratio at emergence
omega	Genotype-specific multiplicative modifier of adult mortality
xiF	Genotype-specific female pupatory success
xiM	Genotype-specific male pupatory success
s	Genotype-specific fractional reduction(increase) in fertility

Details

Female deposition is implemented incorrectly. Right now, it is performed on male alleles prior to zygote formation - it should happen post-zygote formation. Since this construct doesn't have HDR, this should be fine.
Additionally, it is assumed that deposition requries loaded Cas9-RNP complexes from the mother, having Cas9 and no maternal gRNA, even in the presence of paternal gRNA, will not result in maternal deposition mediated cleavage.

Copy-number dependent rates are based on Cas9, not gRNA. The assumption is that RNA is easier to produce, and therefore won't limit cleavage by Cas9.

Value

Named list containing the inheritance cube, transition matrix, genotypes, wild-type allele, and all genotype-specific parameters.

MGDrivE documentation built on Oct. 23, 2020, 7:28 p.m.