A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes

Abstract

Background The Nile rat (Avicanthis niloticus) is an important animal model because of its robust diurnal rhythm, a cone-rich retina, and a propensity to develop diet-induced diabetes without chemical or genetic modifications. A closer similarity to humans in these aspects, compared to the widely used Mus musculus and Rattus norvegicus models, holds the promise of better translation of research findings to the clinic. Results We report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including some that affect genes associated with type 2 diabetes and metabolic dysfunctions. We discuss 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. Conclusions Our findings reflect the exceptional level of genomic resolution present in this assembly, which will greatly expand the potential of the Nile rat as a model organism.

A High-Quality Blue Whale Genome, Segmental Duplications, and Historical Demography

“…Contrary to patterns of recent bursts of SD in primate ( Bailey and Eichler 2006 ) as well as muroid genomes ( Cheung et al 2003 ; Thybert et al 2018 ; Toh et al 2022 ), SDs represent a smaller fraction of genomes in cetartiodactyla. Using the estimated mutation rate of 0.045% bp −1 My −1 ( Jackson et al 2009 ), both the blue whale and vaquita had relatively quiescent genomes until ∼20 M years ago.…”

“…To account for incomplete repeat masking, we also exclude sequences duplicated over 20 times in a genome. The approach to SD annotation used here was developed for vertebrate genomes and previously reported in ( Toh et al 2022 ). It quantifies SD using whole-genome self-alignments ( Numanagic et al 2018 ), and annotates duplicated gene copy numbers by excess read depth and whole-genome multimapping.…”

“…High-quality genomes from long-read assemblies have been shown to resolve more duplicated sequences than short-read assemblies ( Gordon et al 2016 ), indicating this study enables comparative analysis of repetitive DNA and gene copy numbers in cetacean genomes. We applied a computational pipeline recently developed to analyze duplicated genes in rodentia ( Toh et al 2022 ) to assess if there are duplications that could be associated with size differences in cetacea. The vaquita, the world's smallest cetacean, provides a comparison point to the blue whale in terms of body size, while cattle is a terrestrial relative of both species.…”

Scalable, accessible, and reproducible reference genome assembly and evaluation in Galaxy

“…To identify resolved, collapsed, or spurious gene duplications, we mapped HiFi reads to each HiFi assembly, and calculated read depth within RefSeq annotations 20 (Extended data Fig. 1).…”

Plasma metabolomics supports non-fasted sampling for early detection of impaired glucose tolerance in the Nile rat model of type 2 diabetes

“…Fourth, the Nile rat, like humans, are active during the day 12 , unlike common nocturnal rodent models. Additionally, the Nile rat has a reference genome for mechanistic studies 13 . Overall, the Nile rat is highly suited to study the early development of diet-induced diabetes.…”