Liu, E. S. | Search bioRxiv

bioRxiv2020

A pan-genome method to determine core regions of the Bacillus subtilis and Escherichia coli genomes

Synthetic engineering of bacteria to produce industrial products is a burgeoning field of research and application. In order to optimize genome design, designers need to understand which genes are essential, which are optimal for growth, and locations in the genome that will be tolerated by the organism when inserting engineered cassettes. We present a pan-genome based method for the identification of core regions in a genome that are strongly conserved at the species level. We show that these core regions are very likely to contain all or almost all essential genes. We assert that synthetic engineers should avoid deleting or inserting into these core regions unless they understand and are manipulating the function of the genes in that region. Similarly, if the designer wishes to streamline the genome, non-core regions and in particular low penetrance genes would be good targets for deletion. Care should be taken to remove entire cassettes with similar penetrance of the genes within cassettes as they may harbor toxin/antitoxin genes which need to be removed in tandem. The bioinformatic approach introduced here saves considerable time and effort relative to knockout studies on single isolates of a given species and captures a broad understanding of the conservation of genes that are core to a species. ImportanceThe pan-genome approach presented in this paper can be used to determine core regions of a genome and has many possible applications. Synthetic engineering design can be informed by which genes/regions are more conserved (core) versus less conserved. The level of conservation of adjacent non-core genes tends to define cassettes of genes which may be part of a pathway or system that can inform researchers about possible functional significance. The pattern of gene presence across the different genomes of a species can inform the understanding of evolution and horizontal gene acquisition. The approach saves considerable time and effort relative to laboratory methods used to identify essential genes in species.

evolutionary biology↗

bioRxiv2020

Effects of age on pre-stimulus neural activity predictive of successful memory encoding: an fMRI study

Pre-stimulus subsequent memory effects (SMEs) - differences in neural activity preceding the onset of study items that are predictive of later memory performance - have consistently been reported in young adults. The present fMRI experiment investigated potential age-related differences in pre-stimulus SMEs. During study, healthy young and older participants made one of two semantic judgments on images, with the judgment signaled by a preceding cue. In the test phase, participants first made an item recognition judgment and, for each item judged old, a source memory judgment. Age-invariant pre-stimulus SMEs were observed in left dorsomedial prefrontal cortex, left hippocampus, and right subgenual cortex. In each case, the effects reflected lower BOLD signal for later recognized items, regardless of source accuracy, than unrecognized items. A similar age-invariant pattern was observed in left orbitofrontal cortex, but the effect in this region was specific to items attracting a correct source response compared to unrecognized items. In contrast, the left angular gyrus and fusiform cortex demonstrated negative pre-stimulus SMEs that were exclusive to young participants. The findings indicate that age differences in pre-stimulus SMEs are regionally specific and suggest that pre-stimulus SMEs reflect multiple cognitive processes, only some of which are vulnerable to advancing age.

neuroscience↗