Uncertainty in long-run economic growth
Uncertainty in future economic growth can influence climate policy. Image courtesy of iStock/MicroStockHub.
Modeling uncertainty in forecasts of long-run economic growth is an essential part of climate change research that the Intergovernmental Panel on Climate Change (IPCC) has highlighted as a priority. Peter Christensen et al. (pp. 5409–5414) developed comprehensive estimates of the uncertainty in long-run projections of global and regional per capita economic growth rates. The authors used two methods to estimate per capita GDP growth rates and their uncertainties through the year 2100: a survey of 16 experts’ predictions and a statistical method designed to estimate variability in annual average growth rates on the timescale of a decade or longer. The interquartile range of the average global growth rates to 2100 from expert forecasts was 1.4–2.9% per year, while that from the statistical forecasts was 1.7–2.7% per year. Both methods indicated greater uncertainty in long-term growth rates than is assumed in the full range of climate change scenarios, implying a greater likelihood of extreme climate change outcomes than is currently assumed. The authors modeled the distribution of projected greenhouse gas emissions using these long-run growth rates and found a greater than 35% chance of exceeding the highest values assumed in the IPCC’s representative concentration pathways. According to the authors, the large uncertainty about future growth has implications for climate policy and other social programs that rely upon long-run growth forecasts. — B.D.
Reducing resistance to CRISPR gene drives
CRISPR gene drives can rapidly spread an allele through a population, but the drives’ tendency to generate resistance alleles has limited their potential applications. Jackson Champer et al. (pp. 5522–5527) used several Drosophila melanogaster homing gene drive constructs to explore techniques for reducing resistance. The authors found that multiplexing guide RNAs (gRNAs)—where the drive construct contains multiple gRNAs targeting neighboring sites—successfully reduced germline resistance rates and significantly increased drive conversion efficiency. The authors also found that an autosomal drive can successfully achieve gene drive conversion in the male germline without subsequent formation of resistance alleles in the embryo, suggesting that restricting drive activity to the male germline could suppress embryonic resistance allele formation. In addition, gene drives using the nanos promoter had significantly lower formation of somatic resistance alleles than drives using the vasa promoter. The authors report that a drive’s genomic location significantly affected embryonic resistance allele formation but had a relatively small effect on germline drive conversion and resistance allele formation. The authors conclude that gene drives using more than one gRNA represent a promising strategy for reducing resistance allele formation, and the approach may help develop gene drives for use in natural insect populations. — S.R.
Comparison of CRISPR enzymes Cas9 and Cpf1 reveals key similarities, differences
When challenged by foreign genetic material, CRISPR systems provide bacteria with adaptive immunity by storing short sequences of invader DNA in the host genome. This process has been widely repurposed for precision genome engineering, predominantly using the Cas9 enzyme from Streptococcus pyogenes. Digvijay Singh et al. (pp. 5444–5449) describe the kinetics, specificity, mode of action, and product release of CRISPR-Cpf1, a recently identified CRISPR system that remains poorly characterized. Using single-molecule fluorescence analysis and biochemical assays, the authors demonstrate that CRISPR-Cpf1 uses the same method as CRISPR-Cas9 to interrogate DNA and find specific cleavage sites, a two-step process of locating protospacer-adjacent motif sequences followed by RNA-DNA heteroduplex formation and extension. However, unlike Cas9, the authors report, Cpf1 requires far more matching base pairs to stably bind to target cleavage sites; moreover, Cpf1 releases the cleavage products. The findings suggest that Cpf1 can offer a superior alternative to Cas9 for a variety of applications. Further, the findings reveal key similarities and differences between Cpf1 and Cas9 that can be exploited to expand CRISPR-based technologies, according to the authors. — T.J.