A novel broad spectrum venom metalloproteinase autoinhibitor in the rattlesnake evolved via a shift in paralog function.

The complexity of snake venom composition reflects adaptation to the diversity of prey and may be driven at times by a coevolutionary arms race between snakes and venom-resistant prey. However, many snakes are also resistant to their own venom due to serum-borne inhibitors of venom toxins, which raises the question of how snake autoinhibitors maintain their efficacy as venom proteins evolve. To investigate this potential three-way arms race among venom, prey, and autoinhibitors, we have identified and traced the evolutionary origin of serum inhibitors of snake venom metalloproteinases (SVMPs) in the Western Diamondback rattlesnake which possesses the largest known battery of SVMP genes among crotalids examined.

The origin and diversification of a novel protein family in venomous snakes.

The genetic origins of novelty are a central interest of evolutionary biology. Most new proteins evolve from preexisting proteins but the evolutionary path from ancestral gene to novel protein is challenging to trace, and therefore the requirements for and order of coding sequence changes, expression changes, or gene duplication are not clear. Snake venoms are important novel traits that are comprised of toxins derived from several distinct protein families, but the genomic and evolutionary origins of most venom components are not understood.

A major role for noncoding regulatory mutations in the evolution of enzyme activity.

The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number.

Birth-and-Death Evolution of the Fatty Acyl-CoA Reductase (FAR) Gene Family and Diversification of Cuticular Hydrocarbon Synthesis in Drosophila.

The birth-and-death evolutionary model proposes that some members of a multigene family are phylogenetically stable and persist as a single copy over time, whereas other members are phylogenetically unstable and undergo frequent duplication and loss. Functional studies suggest that stable genes are likely to encode essential functions, whereas rapidly evolving genes reflect phenotypic differences in traits that diverge rapidly among species. One such class of rapidly diverging traits are insect cuticular hydrocarbons (CHCs), which play dual roles in chemical communications as short-range recognition pheromones as well as protecting the insect from desiccation.

Extremely Divergent Haplotypes in Two Toxin Gene Complexes Encode Alternative Venom Types within Rattlesnake Species.

Natural selection is generally expected to favor one form of a given trait within a population. The presence of multiple functional variants of traits involved in activities such as feeding, reproduction, or the defense against predators is relatively uncommon within animal species. The genetic architecture and evolutionary mechanisms underlying the origin and maintenance of such polymorphisms are of special interest.

The Deep Origin and Recent Loss of Venom Toxin Genes in Rattlesnakes.

The genetic origin of novel traits is a central but challenging puzzle in evolutionary biology. Among snakes, phospholipase A2 (PLA2)-related toxins have evolved in different lineages to function as potent neurotoxins, myotoxins, or hemotoxins. Here, we traced the genomic origin and evolution of PLA2 toxins by examining PLA2 gene number, organization, and expression in both neurotoxic and non-neurotoxic rattlesnakes.

Expression of tandem gene duplicates is often greater than twofold.

Tandem gene duplication is an important mutational process in evolutionary adaptation and human disease. Hypothetically, two tandem gene copies should produce twice the output of a single gene, but this expectation has not been rigorously investigated. Here, we show that tandem duplication often results in more than double the gene activity.

Gain of cis-regulatory activities underlies novel domains of wingless gene expression in Drosophila.

Changes in gene expression during animal development are largely responsible for the evolution of morphological diversity. However, the genetic and molecular mechanisms responsible for the origins of new gene-expression domains have been difficult to elucidate. Here, we sought to identify molecular events underlying the origins of three novel features of wingless (wg) gene expression that are associated with distinct pigmentation patterns in Drosophila guttifera.

Wax, sex and the origin of species: Dual roles of insect cuticular hydrocarbons in adaptation and mating.

Evolutionary changes in traits that affect both ecological divergence and mating signals could lead to reproductive isolation and the formation of new species. Insect cuticular hydrocarbons (CHCs) are potential examples of such dual traits. They form a waxy layer on the cuticle of the insect to maintain water balance and prevent desiccation, while also acting as signaling molecules in mate recognition and chemical communication.

A single gene affects both ecological divergence and mate choice in Drosophila.

Evolutionary changes in traits involved in both ecological divergence and mate choice may produce reproductive isolation and speciation. However, there are few examples of such dual traits, and the genetic and molecular bases of their evolution have not been identified. We show that methyl-branched cuticular hydrocarbons (mbCHCs) are a dual trait that affects both desiccation resistance and mate choice in Drosophila serrata.

Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila.

Sexual dimorphism is widespread throughout the metazoa and plays important roles in mate recognition and preference, sex-based niche partitioning, and sex-specific coadaptation. One notable example of sex-specific differences in insect body morphology is presented by the higher diptera, such as Drosophila, in which males develop fewer abdominal segments than females. Because diversity in segment number is a distinguishing feature of major arthropod clades, it is of fundamental interest to understand how different numbers of segments can be generated within the same species.

Evolutionary origin of a novel gene expression pattern through co-option of the latent activities of existing regulatory sequences.

Spatiotemporal changes in gene expression underlie many evolutionary novelties in nature. However, the evolutionary origins of novel expression patterns, and the transcriptional control elements ("enhancers") that govern them, remain unclear. Here, we sought to explore the molecular genetic mechanisms by which new enhancers arise.

Generation of a novel wing colour pattern by the Wingless morphogen.

The complex, geometric colour patterns of many animal bodies have important roles in behaviour and ecology. The generation of certain patterns has been the subject of considerable theoretical exploration, however, very little is known about the actual mechanisms underlying colour pattern formation or evolution. Here we have investigated the generation and evolution of the complex, spotted wing pattern of Drosophila guttifera.

Stepwise modification of a modular enhancer underlies adaptation in a Drosophila population.

The evolution of cis regulatory elements (enhancers) of developmentally regulated genes plays a large role in the evolution of animal morphology. However, the mutational path of enhancer evolution--the number, origin, effect, and order of mutations that alter enhancer function--has not been elucidated. Here, we localized a suite of substitutions in a modular enhancer of the ebony locus responsible for adaptive melanism in a Ugandan Drosophila population.

Evolution of the tan locus contributed to pigment loss in Drosophila santomea: a response to Matute et al.

We have shown previously that the loss of abdominal pigmentation in D. santomea relative to its sister species D. yakuba resulted, in part, from cis-regulatory mutations at the tan locus.

Genetic and molecular insights into the development and evolution of sexual dimorphism.

Sexual dimorphism is common throughout the animal kingdom. However, a molecular understanding of how sex-specific traits develop and evolve has been elusive. Recently, substantial progress has been made in elucidating how diverse sex-determination systems are integrated into developmental gene networks.

Rapid evolution of sex pheromone-producing enzyme expression in Drosophila.

A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies.

Evolution of an insect-specific GROUCHO-interaction motif in the ENGRAILED selector protein.

Animal morphology evolves through alterations in the genetic regulatory networks that control development. Regulatory connections are commonly added, subtracted, or modified via mutations in cis-regulatory elements, but several cases are also known where transcription factors have gained or lost activity-modulating peptide motifs. In order to better assess the role of novel transcription factor peptide motifs in evolution, we searched for synapomorphic motifs in the homeotic selectors of Drosophila melanogaster and related insects.

The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila.

Sexually dimorphic traits play key roles in animal evolution and behavior. Little is known, however, about the mechanisms governing their development and evolution. One recently evolved dimorphic trait is the male-specific abdominal pigmentation of Drosophila melanogaster, which is repressed in females by the Bric-à-brac (Bab) proteins.

Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution.

Biologists have long sought to understand which genes and what kinds of changes in their sequences are responsible for the evolution of morphological diversity. Here, I outline eight principles derived from molecular and evolutionary developmental biology and review recent studies of species divergence that have led to a genetic theory of morphological evolution, which states that (1) form evolves largely by altering the expression of functionally conserved proteins, and (2) such changes largely occur through mutations in the cis-regulatory sequences of pleiotropic developmental regulatory loci and of the target genes within the vast networks they control.