Biology subjects

Baum, R.

Publications and source records attributed to Baum, R..

2 recordsLinked to original sources

bioRxiv2020

A genome-scale CRISPR interference guide library enables comprehensive phenotypic profiling in yeast

CRISPR/Cas9-mediated transcriptional interference (CRISPRi) enables programmable gene knock-down, yielding interpretable loss-of-function phenotypes for nearly any gene. Effective, inducible CRISPRi has been demonstrated in budding yeast, but no genome-scale guide libraries have been reported. We present a comprehensive yeast CRISPRi library, based on empirical design rules, containing 10 distinct guides for most genes. Competitive growth after pooled transformation revealed strong fitness defects for most essential genes, verifying that the library provides comprehensive genome coverage. We used the relative growth defects caused by different guides targeting essential genes to further refine yeast CRISPRi design rules. In order to obtain more accurate and robust guide abundance measurements in pooled screens, we link guides with random nucleotide barcodes and carry out linear amplification by in vitro transcription. Taken together, we demonstrate a broadly useful platform for comprehensive, high-precision CRISPRi screening in yeast.

genomics↗

bioRxiv2019

Muntjac chromosome evolution and architecture

AbstractDespite their recent divergence, muntjac deer show striking karyotype differences. Here we describe new chromosome-scale genome assemblies for the Chinese and Indian muntjacs, Muntiacus reevesi (2n=46) and Muntiacus muntjak (2n=6/7), and analyze their evolution and architecture. We identified six fusion events shared by both species relative to the cervid ancestor and therefore present in the muntjac common ancestor, six fusion events unique to the M. reevesi lineage, and twenty-six fusion events unique to the M. muntjak lineage. One of these M. muntjak fusions reverses an earlier fission in the cervid lineage. Although comparative Hi-C analysis revealed differences in long-range genome contacts and A/B compartment structures, we discovered widespread conservation of local chromatin contacts between the muntjacs, even near the fusion sites. A small number of genes involved in chromosome maintenance show evidence for rapid evolution, possibly associated with the dramatic changes in karyotype. Analysis of muntjac genomes reveals new insights into this unique case of rapid karyotype evolution and the resulting biological variation.

genomics↗