Repeated evolution of self-compatibility for reproductive assurance

Sexual reproduction in eukaryotes requires the fusion of two compatible gametes of opposite sexes or mating types. To meet the challenge of finding a mating partner with compatible gametes evolutionary mechanisms such as hermaphroditism and self-fertilisation have repeatedly evolved. Combining insight from comparative genomics, computer simulations and experimental evolution in fission yeast, we shed light on the conditions promoting separate mating types or self-compatibility by mating-type switching. Analogous to multiple independent transitions between switchers and non-switchers in natural populations mediated by structural genomic changes, novel switching genotypes were readily evolving under selection in experimental populations. Detailed fitness measurements accompanied by computer simulations show the benefits and costs of switching during sexual and asexual reproduction governing the occurrence of both strategies in nature. Our findings illuminate the trade-off between the benefits of reproductive assurance and its fitness costs under benign conditions governing the evolution of self-compatibility

Synthetic biology to access and expand nature's chemical diversity

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology — including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits — and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products

SWITCH: a dynamic CRISPR tool for genome engineering and metabolic pathway control for cell factory construction in Saccharomyces cerevisiae

Additional file 1: Figure S1. The SWITCH recombination event triggering substitution of cas9 (human codon optimized) for dcas9 (yeast codon optimized). Figure S2. Confirmation of cas9 integration into the X-3 locus by diagnostic PCR. Figure S3. Control screening in strain S-0 of the three gRNAs tested for swapping cas9. Figure S4. Exploiting SWITCH for marker-free integration into a specific locus. Figure S5. The three assembler fragments used with SWITCH for marker-free integration of the complete naringenin pathway into locus XI-2. Figure S6. Naringenin producers created by SWITCH and assembler. Figure S7. Gene regulation by SWITCH. Figure S8. Implementing SWITCH for TSC13 down regulation. Table S1. The main primers used in this study. Table S2. Plasmid list