Albanna, A. | bioRxiv Science

bioRxiv2024

A draft Arab pangenome reference

Pangenomes represent a significant shift from relying on a single reference sequence to a robust set of assemblies, Arab populations remain significantly underrepresented; hence, we present the first Arab Pangenome Reference (APR) utilizing 53 individuals of diverse Arab ethnicities. We assembled nuclear and mitochondrial pangenomes using 35.27X high-fidelity long reads, 54.22X ultralong reads and 65.46X Hi-C reads yielded contiguous haplotype-phased de novo assemblies of exceptional quality, with an average N50 of 124.28 Mb. We discovered 111.96 million base pairs of novel euchromatic sequences absent from existing human pangenomes, the T2T-CHM13, GRCh38 reference human genomes, and other public datasets. We identified 8.94 million population-specific small variants and 235,195 structural variants within the Arab pangenome. We detected 883 gene duplications including 15.06% associated with recessive diseases and 1,436 bp of novel mitochondrial pangenome sequence. Our study provides a valuable resource for future genomic medicine initiatives in Arab population and other global populations.

genomics↗

bioRxiv2018

Driving the expression of the Salmonella enterica sv Typhimurium flagellum using flhDC from Escherichia coli results in key regulatory and cellular differences.

The flagellar systems of Escherichia coli and Salmonella enterica exhibit a significant level of genetic and functional synteny. Both systems are controlled by the flagellar specific master regulator FlhD4C2. Since the early days of genetic analyses of flagellar systems it has been known that E. coli flhDC can complement a {Delta}flhDC mutant in S. enterica. The genomic revolution has identified how genetic changes to transcription factors and / or DNA binding sites can impact the phenotypic outcome across related species. We were therefore interested in asking: using modern tools to interrogate flagellar gene expression and assembly, what would the impact be of replacing the flhDC coding sequences in S. enterica for the E. coli genes at the flhDC S. entercia chromosomal locus? We show that even though all strains created are motile, flagellar gene expression is measurably lower when flhDCEC are present. These changes can be attributed to the impact of FlhD4C2 DNA recognition and the protein-protein interactions required to generate a stable FlhD4C2 complex. Furthermore, our data suggests that in E. coli the internal flagellar FliT regulatory feedback loop has a marked difference with respect to output of the flagellar systems. We argue due diligence is required in making assumptions based on heterologous expression of regulators and that even systems showing significant synteny may not behave in exactly the same manner.

microbiology↗