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Genome mutagenesis drives the evolution of organisms. Here, we developed a C RISPR-Cas a ssisted r andom m utation (CARM) technique for whole-genome mutagenesis. The method leverages an entirely random gRNA library and SpCas9-NG to randomly damage genomes in a controllable shotgunlike manner that then triggers diverse and abundant mutations via low-fidelity repair. As a proof of principle, CARM was applied to evolve the capacity of Saccharomyces cerevisiae BY4741 to produce β-carotene. After seven rounds of iterative evolution over two months, a β-carotene hyperproducing strain, C7-143, was isolated with a 10.5-fold increase in β-carotene production and 857 diverse genomic mutations that comprised indels, duplications, inversions, and chromosomal rearrangements. Transcriptomic analysis revealed that the expression of 2541 genes of strain C7-143 was significantly altered, suggesting that the metabolic landscape of the strain was deeply reconstructed. In addition, CARM was applied to evolve industrially relevant S. cerevisiae CEN.PK2-1C for S-adenosyl-L-methionine production, which was increased 2.28 times after just one round. Thus, CARM can contribute to increasing genetic diversity to identify new phenotypes that could further be investigated by reverse engineering.

Longstanding scientific efforts have been dedicated to answer why and how our particular intelligence is generated by our brain but not by the brain of other species. However, surprisingly little effort has been made to ask why no other species ever developed an intelligence similar to ours. Here, I explore this question based on genetic and paleontologic evidence. Contrary to the established view, this review suggests that the developmental hurdles alone are not high enough to explain the uniqueness of human intelligence (HI). As an additional explanation I propose that HI is normally not retained by natural selection, because it is, under most conditions, an intrinsically unfavourable trait. This unfavourableness, however, cannot be explained by physical constraints alone; rather, it may also be rooted in the same emotional and social complexity that is necessary for the development of HI. Thus, a major obstacle towards HI may not be solely the development of the required physical assets, but also to cope with harmful individual, social and environmental feedback intrinsically associated with this trait., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Arold ST.)

Longstanding scientific efforts have been dedicated to answer why and how our particular intelligence is generated by our brain but not by the brain of other species. However, surprisingly little effort has been made to ask why no other species ever developed an intelligence similar to ours. Here, I explore this question based on genetic and paleontologic evidence. Contrary to the established view, this review suggests that the developmental hurdles alone are not high enough to explain the uniqueness of human intelligence (HI). As an additional explanation I propose that HI is normally not retained by natural selection, because it is, under most conditions, an intrinsically unfavourable trait. This unfavourableness, however, cannot be explained by physical constraints alone; rather, it may also be rooted in the same emotional and social complexity that is necessary for the development of HI. Thus, a major obstacle towards HI may not be solely the development of the required physical assets, but also to cope with harmful individual, social and environmental feedback intrinsically associated with this trait., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Arold ST.)

Longstanding scientific efforts have been dedicated to answer why and how our particular intelligence is generated by our brain but not by the brain of other species. However, surprisingly little effort has been made to ask why no other species ever developed an intelligence similar to ours. Here, I explore this question based on genetic and paleontologic evidence. Contrary to the established view, this review suggests that the developmental hurdles alone are not high enough to explain the uniqueness of human intelligence (HI). As an additional explanation I propose that HI is normally not retained by natural selection, because it is, under most conditions, an intrinsically unfavourable trait. This unfavourableness, however, cannot be explained by physical constraints alone; rather, it may also be rooted in the same emotional and social complexity that is necessary for the development of HI. Thus, a major obstacle towards HI may not be solely the development of the required physical assets, but also to cope with harmful individual, social and environmental feedback intrinsically associated with this trait., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Arold ST.)