How locally adapted ecotypes are established and maintained within a species is a long-standing question in evolutionary biology. Using forest and prairie ecotypes of deer mice ( Peromyscus maniculatus ), we characterized the genetic basis of variation in two defining traits—tail length and coat color—and discovered a 41-megabase chromosomal inversion linked to both. The inversion frequency is 90% in the dark, long-tailed forest ecotype; decreases across a habitat transition; and is absent from the light, short-tailed prairie ecotype. We implicate divergent selection in maintaining the inversion at frequencies observed in the wild, despite high levels of gene flow, and explore fitness benefits that arise from suppressed recombination within the inversion. We uncover a key role for a large, previously uncharacterized inversion in the evolution and maintenance of classic mammalian ecotypes.

The propagation of Tau pathology in Alzheimer’s disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread.

A long-standing question in evolutionary biology is how differences in multiple traits can evolve quickly and be maintained together during local adaptation. Using forest and prairie ecotypes in deer mice, which differ in both tail length and coat color, we discovered a 41 Mb chromosomal inversion that is strongly linked to variation in both traits. The inversion maintains highly divergent loci in strong linkage disequilibrium and likely originated ~170 kya, long before the forest-prairie divergence ~10 kya. Consistent with a role in local adaptation, inversion frequency is associated with phenotype and habitat across both a local transect and the species range. Still, although eastern and western forest subspecies share similar phenotypes, the inversion is absent in eastern North America. This work highlights the significance of inversion polymorphisms for the establishment and maintenance of multiple locally adaptive traits in mammals, and demonstrates that, even within a species, parallel phenotypes may evolve through nonparallel genetic mechanisms.