ABSTRACT Background The cotton rat ( Sigmodon hispidus ), a rodent species native to the Americas, has emerged as a valuable laboratory model of infections by numerous human pathogens including poliovirus and respiratory syncytial virus (RSV). Results Here we report the first reference assembly of the cotton rat genome organized at a chromosomal level, providing annotation of 24,878 protein-coding genes. Data from PCR-free whole genome sequencing, linked-read sequencing and RNA sequencing from pooled cotton rat tissues were analyzed to assemble and annotate this novel genome sequence. Spectral karyotyping data using fluorescent probes derived from mouse chromosomes facilitated the assignment of cotton rat orthologs to syntenic chromosomes, comprising 25 autosomes and a sex chromosome in the haploid genome. Comparative phylome analysis revealed both gains and losses of numerous genes including immune defense genes against pathogens. We identified thousands of recently retrotransposed L1 and SINE B2 elements, revealing widespread genetic innovations unique to this species. Conclusions We anticipate that annotation and characterization of the first chromosome-level cotton rat genome assembly as described here will enable and accelerate ongoing investigations into its host defenses against viral and other pathogens, genome biology and mammalian evolution.

A chromosome-level genome assembly of the Hispid cotton rat (Sigmodon hispidus), a model for human pathogenic virus infections