Gene Drives on the Horizon Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values (2016) / Chapter Skim
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2 The State of Knowledge of the Molecular Biology, Population Genetics, and Ecology of Gene-Drive Modified Organisms
2 The State of Knowledge of the Molecular Biology, Population Genetics, and Ecology of Gene-Drive Modified Organisms
Pages 26-48
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From page 26... ...
. This chapter has two aims: Outline the state of knowledge on genetic elements and their drive mechanisms; and Describe primary evolutionary and ecological considerations for the development and potential release of gene-drive modified organisms The committee discusses the potential for developing gene drives from both molecular and population biology stand points.
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From page 27... ...
Here, the committee briefly describes the main types of genetic elements that researchers are using to develop gene-drive modified organisms in the laboratory, and potentially for release into the environment. Transposable Elements Transposable elements (TEs)
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Yet, the SD autosomal gene complex is present in the Drosophila melanogaster population at a relatively low frequency (1-5%) for reasons that are not well understood.
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Wild-type females that meet with the transgenic males are either killed or unable to produce offspring, which leads to population suppression (Marshall et al., 2011)
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. Building on the concept of meiotic drive described earlier, Galizi et al.
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FIGURE 2-1 Illustration of th E hree gene editing techn niques. Zinc finger nuc cleases (ZFNs)
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. CRI ISPR/CAS9-B BASED GENE DRIVES E CRISPR/Ca is a genetic engineering to developed from an adapti immune sy as ool f ive ystem like res sponse observe in bacteria and archaea.
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Source: Figu adapted from Esvelt et al., 2014. ure m 2 In 2015 researchers published fou proof-of-co 5, ur oncept studies demonstrating the use of g CRISPR/Cas9 to develop gene drives in the yeast Saccharomyces c 9 g n cerevisiae (Di iCarlo et al., 2015)
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From page 34... ...
Releasing gene drives into the environment means that complex molecular systems will be introduced into complex ecological systems, setting off a cascade of eco-evolutionary dynamics. Key considerations include fitness, species dispersal, gene flow, ecosystem dynamics, and evolution.
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From page 35... ...
For example, when a heterozygous individual always produces gametes with only the drive allele, the conversion rate is 100%. These population genetic models illustrate that the basic dynamics of gene drives are propelled by the conversion rate of the gene drive and the fitness of individuals that have the drive.
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The following sections focus on some of the properties of gene dispersal and its potential effects -- both beneficial and detrimental -- that can inform the application of gene drives and aid in planning their release.
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Understanding gene flow is also vital for estimating the likelihood that the gene drive may move into a non-target population. The diversity of gene flow patterns is influenced by three main factors: the stage of the life cycle in which the movement of individual organisms among populations is most likely, the type of movement through which individuals carry genes among populations, and the spatial scale over which movement typically occurs.
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. The Implications of Gene Flow for Gene Drives Regardless of the type or movement, the spatial scale, or the life stage in which it occurs, gene flow at a sufficient rate can cause populations to converge in gene frequencies (Slatkin, 1985)
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It is difficult at present to model the spread of a gene drive without estimates of important model parameters, including fitness, conversion rate, population structure, gene flow, and ecological interactions among others. Empirical measurements of all of these important parameters are important prerequisites for the release of gene-drive modified organisms.
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From page 40... ...
, suggesting that the possibility of the horizontal exchange of gene drives between species should need to be evaluated prior to environmental release. Removal or Substantial Reduction of a Target Species One possible goal of release a gene-drive modified organism is to cause the extinction of the target species or a drastic reduction in its abundance.
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From page 41... ...
The biggest challenge is the rapidity with which gene drives can spread, because consequences could occur too quickly for any adaptive management scheme to halt them. Many of these points were made in the Ecological Society of America's most recent report on genetically modified organisms in the environment (Snow et al., 2005)
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From page 42... ...
Research on the molecular biology of gene drives has outpaced research on population genetics and ecosystem dynamics, two fields of study that are essential to determining the efficacy of gene drives and their biological and ecological outcomes. There are considerable gaps in knowledge regarding the implications of gene drives for an organism's fitness, gene flow in and among populations, and the dispersal of individuals, and how factors such as mating behavior, population sub-structure, and generation time might influence a gene drive's effectiveness.
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1999. Dispersal, gene flow, and population structure.
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2015. Safeguarding CRISPR-Cas9 gene drives in yeast.
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2015. Gene Drives in Rodents for Invasive Species Control Webinar, October 15, 2015.
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gene flow: Pollen emission, dispersion, and deposi tion.
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2015. Gene drives spread their wings.
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1985. Gene flow in natural populations.
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