All Gene Drives are Not Equal
There are several ways by which alleles (forms or variants of genes) and chromosomes can enhance their transmission relative to other alleles and chromosomes (‘drive’ or ‘gene drive’). Much of the popular attention on transgenes that display gene drive (or gene drive technologies) when introduced into a genome focuses on only one of several ways gene drive can be achieved.
Why are These Differences Important?
It can be important to understand that the phenomenon of gene drive has multiple origins because the characteristics of a transgenic system that displays gene drive will depend on the strategies and mechanisms used for achieving gene drive. Some of these characteristics will impact the expected fate of the transgenes displaying drive over time within populations of organisms that possess them. Furthermore, discussions of risk and anticipated impacts will also be influenced by the types of gene drive being considered.
A Survey of Gene Drive Types
The content here surveys the ways by which gene drive is achieved in nature and at least two of these strategies can be recreated in the laboratory. Although not technically drive or gene drive, the genetic phenomenon of ‘underdominance’ is included here because it is an alternative mechanism to gene drive by which the frequency of a gene or transgene can be increased in a population.
Gene Drive by Interference
Alleles of some genes enhance their transmission to the next generation by interfering with the development or viability of gametes or embryos that do not contain the allele displaying gene drive. There is a growing amount of knowledge about how these alleles affect their non-driving counterparts and it is clear that multiple mechanisms have evolved. When interference occurs during meiosis (cell division leading to the formation of gametes- sperm and egg) the resulting gene drive is often referred to as meiotic drive. But interference can also occur after meiosis and results in a similar outcome – the preferential transmission of an allele over others.
The following short video graphically illustrates the interference strategy.
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Gene Drive by Over-Replication
When an allele (a form or variant of a gene) or chromosome is preferentially transmitted to the next generation, the allele or chromosome is said to be displaying drive or gene drive.
For most alleles and chromosomes transmission to the next generation is not biased or skewed relative to the other corresponding allele or chromosome present in the genome. For alleles of some genes, some chromosomes and other genetic elements such as transposons transmission can be biased and skewed, resulting in drive. One strategy for achieving this transmission advantage is for an allele to make copies of itself and to insert these copies on other chromosomes – referred to as over-replication. This video illustrates how this strategy works.
This short video graphically illustrates the over-replication strategy for attaining a transmission advantage (drive).
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Gene Drive by Gonotaxis
When females produce eggs it involves meiosis, a cell division that halves the genome, and results often in 4 cells – 1 egg and 3 “polar bodies”. The polar bodies are cells much reduced in size relative to the egg that often will degenerate following their formation. In some organisms polar bodies may survive to contribute some reproductive functions but they are not functional eggs. The default patterns of inheritance result in chromosomes having a 50:50 chance of ending up in the egg and pole cells. But there are exceptions where one of a pair of chromosomes has more than a fair chance of ending up in an egg – a phenomenon known as gonotaxis or asymmetric meiosis. Chromosomes with those characteristics have a transmission advantage and display drive.
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This video (03:45) illustrates a proposed mechanism by which gonotaxis occurs based on studies in mice reported by Akera et al (2017).
Underdominance
Underdominance is a somewhat obtuse term in genetics that refers to a situation where individuals that carry two different alleles of a gene (heterozygotes) are less fit than those that carry two identical alleles (homozygotes). While not technically gene drive this phenomenon can have interesting consequences on the frequency of alleles that display underdominance and can, in theory, be used to introduce a genetic modification into a population and have it reach high frequencies, an outcome also achieved using gene drive.
The following video graphically illustrates what underdominance is and how it might be used to introduce a transgene into a population so that it reaches high frequencies.
