Appendix 1: Examples of natural and synthetic gene drive mechanisms

Homing endonuclease genes

Site-specific selfish genes such as homing endonuclease genes (HEGs) can spread through populations as a gene drive due to their biased inheritance (Burt, 2003). They cleave a unique stretch of genomic DNA and as the cell repairs the hydrolysed DNA the HEG is copied into the cleaved site. Consequently the frequency of HEGs increases and they spread throughout a population.

There are other current gene editing techniques such as Zinc Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs) and CRISPR (Clustered regularly interspaced short palindromic repeats) which also utilise nucleases to cleave at specific sites. While not a gene drive in its own right, CRISPR/Cas9 is a gene editing tool that can be used to produce synthetic gene drives that increase the inheritance of a particular trait as outlined in the main text. Note that the vast majority of gene editing applications does not involve the creation of a gene drive.

Transporsable elements

Gene drives can be generated by manipulating transposable elements, also known as jumping genes. These are small DNA segments which can excise themselves and randomly insert into different parts of the genome. This results in multiple copies within the genome. The P-element transposon is a type of transposable element well studied in the Drosophila melanogaster (Rubin & Spradling, 1982). An active P-element can be modified and in this way can rapidly spread the modified sequence throughout a population.

Meiotic drive

Meiotic drive is a gene drive mechanism interfering with meiotic processes to cause a distortion of allelic segregation compared to expected Mendelian inheritance (McDermott & Noor, 2010). This has been reported in Drosophila melanogaster, in the house mouse Mus musculus and in plants Zea mays and Silene. Within Zea mays the Abnormal 10 (Ab10) chromosome affects segregation of chromosome 10 and causes heterozygous chromosomal pair separation of 70% rather than the typical 50% expected with Mendelian inheritance.

Underdominance

Underdominance is selection against heterozygous progeny where the homozygotes have an increased fitness and one of the homozygous forms can be driven to a high frequency. Underdominance was proposed as a method of controlling sheep blowfly in Australia several decades ago (Whitten, 1971). Current approaches for establishing underdominance have been achieved by RNA interference in Drosophila melanogaster to suppress an endogenous gene (Reeves et al., 2014).

Maternal-effect dominant embryonic arrest

Maternal-effect dominant embryonic arrest (Medea) can be used to suppress a population by targeting and silencing a maternal gene necessary for embryonic development. This was first discovered in a flour beetle and causes death in any offspring that lack the Medea-bearing chromosome (Beeman et al., 1992), allowing the Medea element to spread.

Cytoplasmic incompatibility

Wolbachia are bacteria that manipulate the reproduction of a diverse range of arthropod hosts to their own advantage (Sinkins & Gould, 2006). They are a common intracellular microbe which can generate a gene drive in infected host individuals by triggering incompatibility between eggs and sperm or by male killing. They are maternally inherited and change the population dynamics to favour infected females. A rescue function allows eggs from infected females to develop normally when mated to infected males. Current research trials on release of mosquitoes which carry Wolbachia have focused on preventing the spread of viruses such as Zika and dengue whose transmission is suppressed by Wolbachia. However these bacteria could also be used to potentially spread genes engineered into Wolbachia or other maternally transmitted factors such as mitochondria.

Cytoplasmic male sterility

Cytoplasmic male sterility is another form of non-Mendelian inheritance (Laughnan & Gabay-Laughnan, 1983). This condition is widespread among higher plants and results in a plant unable to produce functional pollen, i.e. male sterile, due to a sterility inducing mitochondrial gene which is maternally inherited. This is used extensively in agriculture to generate hybrid seed, these seeds usually result in larger, more vigorous plants.

© 2019 Australian Academy of Science

Top