Forest-dwelling deer mice (Peromyscus maniculatus) can be distinguished from their prairie-roaming counterparts by their longer tails and their darker coat color, which helps them blend into a woodland environment. A new analysis from the Hoekstra Lab, published in the journal Science (PDF), found that both of these traits are located on a stretch of DNA that went through a type of DNA rearrangement called a chromosomal inversion.
In a chromosomal inversion, a DNA segment breaks away from its chromosome and then reattaches in the reverse orientation. This type of rearrangement can radically change the order of base pairs for many genes at once. Such inversions often block recombination, creating isolated genomic regions that are passed down as a whole set.
Researchers from the Hoekstra Lab, led by then MCO graduate student and current BU postdoc Emily Hager and Biophysics graduate student Olivia Harringmeyer, found evidence of a large chromosomal inversion in deer mice. The rearranged segment of DNA is about 40 million base pairs long and contains dozens of genes.
The team began by collecting deer mice from two neighboring populations in Oregon. One set of deer mice hailed from a wooded area in Siuslaw National Forest, while the other came from a sagebrush prairie area near Baker City, Oregon. Their goal was to characterize the genetic bases of traits, such as coat color and tail length, that help deer mice adapt to forests.
The researchers took the deer mice back to their lab, where they crossbred them to produce heterozygous mice. Then they crossed the heterozygous mice to produce offspring with a range of genotypes. Data from the second generation lab crosses revealed that a single large region of chromosome 15 was strongly associated with both coat color and tail length, and vanishingly little recombination was occurring across this region of the chromosome. The absence of genetic recombination often indicates the presence of a structural rearrangement, such as an inversion, the researchers explain.
Long-read DNA sequencing revealed that the structural anomaly was, in fact, a chromosomal inversion.
“It was exciting to find this example of an inversion linked to two adaptive traits in a classic mammalian system, highlighting how—in addition to considering SNPs [single nucleotide polymorphisms]—it’s important to account for structural genomic changes and their role in adaptation,” says Harringmeyer. Sequencing of wild deer mice revealed that about 90% of forest deer mice carried the chromosomal inversion, while the vast majority of prairie deer mice did not. Instead, the prairie-dwellers had the older, non-inverted allele.
Hager says these results help address longstanding questions about how ecotypes with many different traits are maintained in the wild. This particular chromosomal inversion explains how sets of complementary genes that help deer mice adapt to forest settings are passed down from generation-to-generation, despite interbreeding between populations from nearby environments.
“It helps us understand how differences in many traits can be maintained between populations that are relatively close both geographically and genetically, but that live and survive in very different habitats,” Hager says.
by Olivia Harringmeyer, Emily Hager, and Diana Crow
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