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

Abstract

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.

No excess of cis -regulatory variation associated with intra-specific selection in wild pearl millet ( Cenchrus americanus )

“…While our study helped investigate the contribution of cis -regulatory divergence to adaptive traits, technical advances will enable us to advance our understanding of the genetic basis of phenotypic evolution, for example by investigating the role of isoforms in adaptive evolution (Gao et al. 2015; Mallarino et al. 2016) and offer an integrative view of the interactions between regulatory mechanisms and alternative transcription.…”

Morphological Evolution Repeatedly Caused by Mutations in Signaling Ligand Genes

“…Fine mapping of this variation revealed that not only the Agouti locus is the major driver of pigment variation (Manceau et al 2011) but also this genetic region decomposes itself into multiple noncoding sub-loci, each tightly associated with parts of the total phenotype (Linnen et al 2013). Various regulatory elements are involved in directing the expression of three alternative isoforms into different body regions (Mallarino et al 2016). Each adaptive allele is a complex haplotype that is inherited as a package that underwent multiple local changes.…”

The Evolutionary History of Nebraska Deer Mice: Local Adaptation in the Face of Strong Gene Flow

“…The hair-cycle isoform, containing noncoding exons 1B/1C, is expressed in both the dorsal and ventral dermis during hair growth, and is required for forming light, pheomelanin bands on individual hairs ( Bultman et al 1994 ; Vrieling et al 1994 ). In Peromyscus , these same isoforms are present as well as additional, novel isoforms ( Mallarino et al 2017 ). Isoform-specific changes in Agouti expression are associated with changes in the dorsal–ventral boundary (ventral isoform; Manceau et al 2011 ) and the width of light bands on individual hairs (hair-cycle isoform; Linnen et al 2009 ).…”