Researchers led by Peter Doris at UTHealth Houston have produced the first telomere-to-telomere assembly of the brown rat genome, published in Cell Genomics. The complete, unbroken sequences for all 22 chromosome pairs provide a comprehensive genetic reference that resolves regions previously missing or ambiguous in earlier assemblies.
The new assembly reveals more than 60 previously undetected genes, many located in duplicated regions that were difficult to distinguish with older sequencing methods. These genes are thought to be involved in immunity and other biological processes, expanding the known functional landscape of the rat genome.
A striking difference from humans and most other mammals appears in the sex chromosomes. The pseudoautosomal region (PAR), which in humans contains about 20 shared genes that allow X and Y chromosomes to pair and replicate, has been lost from the rat X and Y chromosomes. Instead, the PAR genes have relocated to autosomes, and new sequences enable the rat X and Y to pair head-to-tail rather than head-to-head.
Doris noted that this discovery shows sexual reproduction in rats operates through a different chromosomal mechanism than in humans, a distinction only detectable with a complete, high-quality genome assembly. The finding has direct implications for interpreting reproductive and genetic studies that use rats as models.
To capture genetic diversity across the species, the team generated eight reference-quality assemblies from different rat strains and constructed a pangenome. This pangenome adds approximately 7% more sequence to the species-level genome, allowing researchers to compare variation at any locus across multiple genetic backgrounds simultaneously.
The pangenome reveals functional divergence in duplicated genes; for example, a protease gene involved in digestion has a duplicated copy that has specialized for an immune function. Such insights were previously inaccessible because nearly identical gene copies could not be resolved independently.
The complete assembly and pangenome provide a clearer map for preclinical disease research. Scientists can now more accurately trace genetic contributions to conditions such as heart disease, kidney disease, hypertension, and stroke without the confounding gaps and collapsed duplications that limited earlier references.
Telomere-to-telomere brown rat genome could sharpen disease research models
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