Abstract
The African grass or Nile rat (NR) (Arvicanthis niloticus) is a herbivorous diurnal rodent which is used as a biological model for research on type 2 diabetes mellitus (T2DM) and the circadian rhythm. Similar to humans, male NRs develop T2DM with high-carbohydrate diets. The NR thus provides a unique opportunity to identify the nutritional and underlying genetic factors that characterise human T2DM, as well as the effects of potential anti-diabetic phytochemicals such as Water-Soluble Palm Fruit Extract. Whole genome sequencing (WGS) could help identify possible genetic causes why NRs spontaneously develop T2DM in captivity. In this study, we performed WGS on a hepatic deoxyribonucleic acid (DNA) sample isolated from a male NR using PacBio high-fidelity long-read sequencing. The WGS data obtained were then de novo assembled and annotated using PacBio HiFi isoform sequencing (Iso-Seq) data as well as previous Illumina RNA sequencing (RNA-Seq) data. Genes related to insulin and circadian rhythm pathways were present in the NR genome, similar to orthologues in the rat, mouse and human genomes. T2DM development in the NR is thus most likely not attributable to structural differences in these genes when compared to other biological models. Further studies are warranted to gain additional insights on the genetic-environmental factors which underlie the genetic permissiveness of NRs to develop T2DM.
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Data availability
The data generated in the present study are available in the European Nucleotide Archive repository, https://www.ebi.ac.uk/ena/ (Study accession number: PRJEB54916). The relevant Supplementary Material files are available in the online version of this article.
Code availability
Not applicable.
Abbreviations
- cAMP:
-
cyclic adenosine monophosphate
- CCS:
-
Circular Consensus Sequence
- cGMP:
-
Cyclic guanosine monophosphate
- HiFi:
-
high-fidelity
- Iso-Seq:
-
isoform sequencing
- NR:
-
Nile rat
- RNA-Seq:
-
RNA sequencing
- SCN:
-
suprachiasmatic nucleus
- T2DM:
-
type 2 diabetes mellitus
- WGS:
-
whole genome sequencing
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Acknowledgements
The authors thank Bumjoon Park and Inwon Jang for their technical assistance in the care and data collection related to the NR breeding colony in Brandeis University.
Funding
This research was funded by the Malaysian Palm Oil Board and the Eleventh Malaysia Plan (RMK11) PROFENOLIS (2011101805) budget, as well as the Brandeis University Foster Biomedical Research Laboratory funds for research and teaching.
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S-SL: coordinated the DNA and RNA sample preparations, functionally interpreted the experimental data and wrote the manuscript. J-SK, S-MN, W-KL and C-CH: designed and coordinated the WGS and Iso-Seq experiments and bioinformatics analyses, as well as performed the genome assembly and annotation. SF: was involved in the interpretation of the experimental data. RS: conceived the WGS study and was also involved in the interpretation of the experimental data. KCH: conceived the related animal study, as well as supervised the animal sample collection. All authors participated in helpful discussions and read as well as approved the final manuscript.
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All animal protocols were approved by the Brandeis University Institutional Animal Care and Use Committee, with national and institutional guidelines for the care and use of laboratory animals carefully followed.
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Leow, SS., Khoo, JS., Ng, SM. et al. Insulin and circadian rhythm genes of the Nile rat (Arvicanthis niloticus) are conserved and orthologous to those in the rat, mouse and human. Genetica 152, 11–29 (2024). https://doi.org/10.1007/s10709-023-00202-z
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DOI: https://doi.org/10.1007/s10709-023-00202-z