Person:

Hoekstra, Hopi

A complete understanding of the role of natural selection in driving evolutionary change requires accurate estimates of the strength of selection acting in the wild. Accordingly, several approaches using a variety of data—including patterns of DNA variability, spatial and temporal changes in allele frequencies, and fitness estimates—have been developed to identify and quantify selection on both genotypes and phenotypes. Here, we review these approaches, drawing on both recent and classic examples to illustrate their utility and limitations. We then argue that by combining estimates of selection at multiple levels—from individual mutations to phenotypes—and at multiple timescales—from ecological to evolutionary—with experiments that demonstrate why traits are under selection, we can gain a much more complete picture of the adaptive process.

How do proteins evolve novel functions? To address this question, we are studying the evolution of a mammalian toxin, the serine protease BLTX [1], from the salivary glands of the North American shrew Blarina brevicauda. Here, we examine the molecular changes responsible for promoting BLTX toxicity. First, we show that regulatory loops surrounding the BLTX active site have evolved adaptively via acquisition of small insertions and subsequent accelerated sequence evolution. Second, these mutations introduce a novel chemical environment into the catalytic cleft of BLTX. Third, molecular-dynamic simulations show that the observed changes create a novel chemical and physical topology consistent with increased enzyme catalysis. Finally, we show that a toxic serine protease from the Mexican beaded lizard (GTX) [2] has evolved convergently through almost identical functional changes. Together, these results suggest that the evolution of toxicity might be predictable—arising via adaptive structural modification of analogous labile regulatory loops of an ancestral serine protease—and thus might aid in the identification of other toxic proteins.

A major goal in evolutionary biology is to understand how and why populations differentiate, both genetically and phenotypically, as they invade a novel habitat. A classical example of adaptation is the pale colour of beach mice, relative to their dark mainland ancestors, which colonized the isolated sandy dunes and barrier islands on Florida's Gulf Coast. However, much less is known about differentiation among the Gulf Coast beach mice, which comprise five subspecies linearly arrayed on Florida's shoreline. Here, we test the role of selection in maintaining variation among these beach mouse subspecies at multiple levels—phenotype, genotype and the environments they inhabit. While all beach subspecies have light pelage, they differ significantly in colour pattern. These subspecies are also genetically distinct: pair-wise Fst-values range from 0.23 to 0.63 and levels of gene flow are low. However, we did not find a correlation between phenotypic and genetic distance. Instead, we find a significant association between the average ‘lightness’ of each subspecies and the brightness of the substrate it inhabits: the two most genetically divergent subspecies occupy the most similar habitats and have converged on phenotype, whereas the most genetically similar subspecies occupy the most different environments and have divergent phenotypes. Moreover, allelic variation at the pigmentation gene, Mc1r, is statistically correlated with these colour differences but not with variation at other genetic loci. Together, these results suggest that natural selection for camouflage—via changes in Mc1r allele frequency—contributes to pigment differentiation among beach mouse subspecies.

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.

Charles Darwin's 1859 book On the Origin of Species is much referenced, especially in this double anniversary year. But, does anyone still read it? And, if so, what is the book itself like as a text? We have asked biologists from a range of fields — evolutionary biologists, but also geneticists, ecologists, paleontologists and molecular biologists — to re-read (or read) The Origin for Current Biology. Below are the responses, contributed by: Andrew Berry, Matthew Cobb, Simon Conway Morris, Jerry Coyne, Hopi Hoekstra, Peter Lawrence, Robert May, Christiane Nüsslein-Volhard, Mark Ptashne, Matt Ridley and Marlene Zuk.

The evolutionary history of most behaviours remains unknown. Here, we assay burrowing behaviour of seven species of deer mice in standardized environments to determine how burrowing evolved in this genus (Peromyscus). We found that several, but not all, species burrow even after many generations of captive breeding. Specifically, there were significant and repeatable differences in both the frequency of burrowing and burrow shape between species. Moreover, these observed species-specific behaviours resemble those reported in wild mice. These results suggest that there is probably a strong genetic component to burrowing in deer mice. We also generated a phylogeny for these seven species using characters from four mtDNA and two autosomal loci. Mapping burrowing behaviour onto this phylogeny suggests a sequence for how complex burrowing evolves: from small, simple burrows to long, multitunnel burrows with defined entrance and escape tunnels. In particular, the most ‘complex’ burrows of P. polionotus appear to be derived. These behavioural data, when examined in a phylogenetic context, show that even closely related species differ in their burrowing behaviours and that the most complex burrows probably evolved by the gradual accumulation of genetic change over time.

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.