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. 2017 Dec 7;11(5):718-726.
doi: 10.1111/eva.12572. eCollection 2018 Jun.

Genomic analyses identify multiple Asian origins and deeply diverged mitochondrial clades in inbred brown rats (Rattus norvegicus)

Emily E Puckett  1 , Olivia Micci-Smith  1 , Jason Munshi-South  1
Affiliations

Genomic analyses identify multiple Asian origins and deeply diverged mitochondrial clades in inbred brown rats (Rattus norvegicus)

Emily E Puckett et al. Evol Appl. .

Abstract

Over 500 strains of inbred brown rats (Rattus norvegicus) have been developed for use as a biomedical model organism. Most of these inbred lines were derived from the colony established at the Wistar Institute in 1906 or its descendants following worldwide distribution to research and breeding centers. The geographic source of the animals that founded the Wistar colony has been lost to history; thus, we compared 25 inbred rat strains to 326 wild rats from a global diversity dataset at 32 k SNPs, and 47 mitochondrial genomes to identify the source populations. We analyzed nuclear genomic data using principal component analyses and co-ancestry heat maps, and mitogenomes using phylogenetic trees and networks. In the nuclear genome, inbred rats clustered together indicating a single geographic origin for the strains studied and showed admixed ancestral variation with wild rats in eastern Asia and western North America. The Sprague Dawley derived, Wistar derived, and Brown Norway strains each had mitogenomes from different clades which diverged between 13 and 139 kya. Thus, we posit that rats originally collected for captive breeding had high mitochondrial diversity that became fixed through genetic drift and/or artificial selection. Our results show that these important medical models share common genomic ancestry from a few source populations, and opportunities exist to create new strains with diverse genomic backgrounds to provide novel insight into the genomic basis of disease phenotypes.

Keywords: inbreeding; mitogenomes; mitonuclear discordance; rat strains.

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Figures

Figure 1
Figure 1
Principal component analyses of (a) the global diversity dataset (n = 326) of 32k SNPs and the inbred samples (n = 29; black) projected into the PC space for the first and third axes, (b) the inbred samples labeled (see Table S1) from the same projection. Sample colors indicate genomic clustering, including China (dark brown), South‐East Asia (light brown), eastern Russia (pink), Aleutian Archipelago (orange), Western North America (yellow), Northern Europe (purple), Western Europe and global expansion (light blue), and Haida Gwaii, Canada (dark blue)
Figure 2
Figure 2
Co‐ancestry heat map of Rattus norvegicus (global diversity dataset n = 326; inbred n = 29) using 32k SNPs from the nuclear genome analyzed in FINESTRUCTURE, where yellow and black, respectively, denote lower and higher co‐ancestry
Figure 3
Figure 3
Network of Rattus norvegicus mitogenomes denoting either the geographic location of strain of wild and inbred rats, respectively (see Table S1). The name of each clade is listed in bold
Figure 4
Figure 4
Phylogenetic tree of Rattus norvegicus mitochondrial genomes with Rattus and Mus outgroups removed for legibility (see Figure S3 for tree with outgroups). See Table 1 for posterior support, divergence times, and 95% HPD for each node
See this image and copyright information in PMC

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