Abstract
Background This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome.MethodsWe simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance (sigma_{A}^{2} ), rate of change in inbreeding (Delta F), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles.ResultsGene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain.ConclusionsGenome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding.
Highlights
This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs
The breeder was given the choice of using only selection, selection and genome editing, or selection and genome editing with gene drives
Genetic gain Gene drives amplify the increase in genetic gain brought about by genome editing
Summary
This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. This paper uses simulation to explore how gene drives increase genetic gain in livestock breeding programs. Genetic gain is brought about by increasing the frequency of favourable alleles. The increase in frequency is achieved slowly by selecting high merit individuals as the parents of the generation. Recent advances in genome editing have increased interest in using this technology to accelerate genetic gain in breeding programs [1]. Genome editing allows the precise deletion, addition or change of alleles at specific locations in the genome of a cell. There are over 300 examples of the use of genome editing in plants and livestock [2], including edits for herbicide resistance in oilseed rape [3], in the myostatin gene for “double muscling” in pigs, cattle and sheep [4], the introduction of the polled gene into dairy cattle [5], and edits to confer resistance to porcine reproductive and respiratory syndrome virus (PRRS) and African swine fever virus (ASFV) in pigs [4, 6,7,8]
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