The role of isoforms in the evolution of cryptic coloration in Peromyscus mice

Ricardo Mallarino, Tess A. Linden, Catherine R. Linnen, Hopi E. Hoekstra

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


A central goal of evolutionary biology is to understand the molecular mechanisms underlying phenotypic adaptation. While the contribution of protein-coding and cis-regulatory mutations to adaptive traits has been well documented, additional sources of variation – such as the production of alternative RNA transcripts from a single gene, or isoforms – have been understudied. Here, we focus on the pigmentation gene Agouti, known to express multiple alternative transcripts, to investigate the role of isoform usage in the evolution of cryptic colour phenotypes in deer mice (genus Peromyscus). We first characterize the Agouti isoforms expressed in the Peromyscus skin and find two novel isoforms not previously identified in Mus. Next, we show that a locally adapted light-coloured population of P. maniculatus living on the Nebraska Sand Hills shows an upregulation of a single Agouti isoform, termed 1C, compared with their ancestral dark-coloured conspecifics. Using in vitro assays, we show that this preference for isoform 1C may be driven by isoform-specific differences in translation. In addition, using an admixed population of wild-caught mice, we find that variation in overall Agouti expression maps to a region near exon 1C, which also has patterns of nucleotide variation consistent with strong positive selection. Finally, we show that the independent evolution of cryptic light pigmentation in a different species, P. polionotus, has been driven by a preference for the same Agouti isoform. Together, these findings present an example of the role of alternative transcript processing in adaptation and demonstrate molecular convergence at the level of isoform regulation.

Original languageEnglish
Pages (from-to)245-258
Number of pages14
JournalMolecular Ecology
Issue number1
StatePublished - Jan 1 2017

Bibliographical note

Funding Information:
We thank Judy Chupasko and Mark Omura for help with specimen preparation, Catalina Perdomo for advice and assistance with luciferase assays, Nicole Bedford for collecting samples for Santa Rosa Island Beach mice, and Nikki Hughes for providing logistical support. RM and his molecular work was supported by a Swiss National Science Foundation grant to HEH. TAL was supported by a Herchel Smith-Harvard Undergraduate Research Fellowship; CRL was supported by a Ruth Kirschstein National Research Service Award from NIH; HEH is an Investigator of the Howard Hughes Medical Institute. This work was supported by a grant from the Swiss National Science Foundation.

Publisher Copyright:
© 2016 John Wiley & Sons Ltd


  • development and evolution
  • ecological genetics
  • gene structure and function
  • mammals
  • molecular evolution
  • population genetics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics


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