Person:

Kingsley, Evan

Adaptation is a central focus of biology, although it can be difficult to identify both the strength and agent of selection and the underlying molecular mechanisms causing change. We studied cryptically colored deer mice living on the Nebraska Sand Hills and show that their light coloration stems from a novel banding pattern on individual hairs produced by an increase in Agouti expression caused by a cis-acting mutation (or mutations), which either is or is closely linked to a single amino acid deletion in Agouti that appears to be under selection. Furthermore, our data suggest that this derived Agouti allele arose de novo after the formation of the Sand Hills. These findings reveal one means by which genetic, developmental, and evolutionary mechanisms can drive rapid adaptation under ecological pressure.

Understanding both the role of selection in driving phenotypic change and its underlying genetic basis remain major challenges in evolutionary biology. Here, we use modern tools to revisit a classic system of local adaptation in the North American deer mouse, Peromyscus maniculatus, which occupies two main habitat types: prairie and forest. Using historical collections, we find that forest‐dwelling mice have longer tails than those from nonforested habitat, even when we account for individual and population relatedness. Using genome‐wide SNP data, we show that mice from forested habitats in the eastern and western parts of their range form separate clades, suggesting that increased tail length evolved independently. We find that forest mice in the east and west have both more and longer caudal vertebrae, but not trunk vertebrae, than nearby prairie forms. By intercrossing prairie and forest mice, we show that the number and length of caudal vertebrae are not correlated in this recombinant population, indicating that variation in these traits is controlled by separate genetic loci. Together, these results demonstrate convergent evolution of the long‐tailed forest phenotype through two distinct genetic mechanisms, affecting number and length of vertebrae, and suggest that these morphological changes—either independently or together—are adaptive.

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought.

Variation in the shape, size, and number of segments along the vertebral column underlies a vast amount of vertebrate diversity. Although the molecular pathways controlling vertebrate segmentation during normal development are well understood, the genetic and developmental underpinnings responsible for the tremendous variation in size and number of vertebrae are relatively unexplored. The main goal of this dissertation is to explore the genetic and developmental mechanisms influencing naturally occurring variation in the vertebral column. To this end, I focus on intraspecific skeletal variation, with an emphasis on tail length, in the deer mouse, Peromyscus maniculatus. In Chapter 1, I employ a phylogeographic framework to show that longer tails have evolved independently in different populations of forest-dwelling mice. Closer investigation of the underlying morphology shows that long-tailed mice have both (1) a greater number of tail vertebrae and (2) individually longer vertebrae, compared to ancestral short-tailed mice. Chapter 2 explores the genetic basis of tail length variation. I use quantitative trait locus mapping to uncover six loci that influence differences in total tail length (3 associated with vertebral length and 3 with vertebrae number). Finally, in Chapter 3 I combine comparative data from quantitative measurements of tissue dynamics during somitogenesis in fixed embryos and ex vivo explant culture to show that embryos of forest mice make more segments because they produce more presomitic mesoderm, and not because of any significant difference in the timing of somitogenesis. Together, this work integrates phylogeographic, genetic, and developmental studies to pinpoint the ways that natural selection modifies development to produce the repeated evolution of an evolutionarily important trait, and suggests that there are a limited number of ways that long tails can evolve.