Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication.

Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication. To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data. Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.

Canine behavioral genetics: pointing out the phenotypes and herding up the genes.

An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, tracking, hunting, and so forth are likely to be controlled, at least in part, at the genetic level. Recent studies in canine genetics suggest that small numbers of genes control major morphologic phenotypes. By extension, we hypothesize that at least some canine behaviors will also be controlled by small numbers of genes that can be readily mapped. In this review, we describe our current understanding of a representative subset of canine behaviors, as well as approaches for phenotyping, genome-wide scans, and data analysis. Finally, we discuss the applicability of studies of canine behavior to human genetics.

Visual sensitivities tuned by heterochronic shifts in opsin gene expression.

BACKGROUND: Cichlid fishes have radiated into hundreds of species in the Great Lakes of Africa. Brightly colored males display on leks and vie to be chosen by females as mates. Strong discrimination by females causes differential male mating success, rapid evolution of male color patterns and, possibly, speciation. In addition to differences in color pattern, Lake Malawi cichlids also show some of the largest known shifts in visual sensitivity among closely related species. These shifts result from modulated expression of seven cone opsin genes. However, the mechanisms for this modulated expression are unknown. RESULTS: In this work, we ask whether these differences might result from changes in developmental patterning of cone opsin genes. To test this, we compared the developmental pattern of cone opsin gene expression of the Nile tilapia, Oreochromis niloticus, with that of several cichlid species from Lake Malawi. In tilapia, quantitative polymerase chain reaction showed that opsin gene expression changes dynamically from a larval gene set through a juvenile set to a final adult set. In contrast, Lake Malawi species showed one of two developmental patterns. In some species, the expressed gene set changes slowly, either retaining the larval pattern or progressing only from larval to juvenile gene sets (neoteny). In the other species, the same genes are expressed in both larvae and adults but correspond to the tilapia adult genes (direct development). CONCLUSION: Differences in visual sensitivities among species of Lake Malawi cichlids arise through heterochronic shifts relative to the ontogenetic pattern of the tilapia outgroup. Heterochrony has previously been shown to be a powerful mechanism for change in morphological evolution. We found that altering developmental expression patterns is also an important mechanism for altering sensory systems. These resulting sensory shifts will have major impacts on visual communication and could help drive cichlid speciation.

An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs.

Retrotransposition of processed mRNAs is a common source of novel sequence acquired during the evolution of genomes. Although the vast majority of retroposed gene copies, or retrogenes, rapidly accumulate debilitating mutations that disrupt the reading frame, a small percentage become new genes that encode functional proteins. By using a multibreed association analysis in the domestic dog, we demonstrate that expression of a recently acquired retrogene encoding fibroblast growth factor 4 (fgf4) is strongly associated with chondrodysplasia, a short-legged phenotype that defines at least 19 dog breeds including dachshund, corgi, and basset hound. These results illustrate the important role of a single evolutionary event in constraining and directing phenotypic diversity in the domestic dog.

Coat variation in the domestic dog is governed by variants in three genes.

Coat color and type are essential characteristics of domestic dog breeds. Although the genetic basis of coat color has been well characterized, relatively little is known about the genes influencing coat growth pattern, length, and curl. We performed genome-wide association studies of more than 1000 dogs from 80 domestic breeds to identify genes associated with canine fur phenotypes. Taking advantage of both inter- and intrabreed variability, we identified distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R-spondin-2, fibroblast growth factor-5, and keratin-71, respectively), that together account for most coat phenotypes in purebred dogs in the United States. Thus, an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes.

Evolution of the cichlid visual palette through ontogenetic subfunctionalization of the opsin gene arrays.

The evolution of cone opsin genes is characterized by a dynamic process of gene birth and death through gene duplication and loss. However, the forces governing the retention and death of opsin genes are poorly understood. African cichlid fishes have a range of ecologies, differing in habitat and foraging style, which make them ideal for examining the selective forces acting on the opsin gene family. In this work, we present data on the riverine cichlid, Oreochromis niloticus, which is an ancestral outgroup to the cichlid adaptive radiations in the Great African lakes. We identify 7 cone opsin genes with several instances of gene duplication. We also characterize the spectral sensitivities of these genes through reconstitution of visual pigments. Peak absorbances demonstrate that each tilapia cone opsin gene codes for a spectrally distinct visual pigment: SWS1 (360 nm), SWS2b (423 nm), SWS2a (456 nm), Rh2b (472 nm), Rh2a beta (518 nm), Rh2a alpha (528 nm), and LWS (561 nm). Furthermore, quantitative reverse transcription polymerase chain reaction at 3 ontogenetic time points demonstrates that although only 4 genes (SWS2a, Rh2a alpha and beta, and LWS) are expressed in adults, mRNAs for the other genes are all expressed during ontogeny. Therefore, subfunctionalization through differential ontogenetic expression may be a key mechanism for preservation of opsin genes. The distinct peak absorbances of these preserved opsin genes provide a palette from which selection creates the diverse visual sensitivities found among the cichlid species of the lacustrine adaptive radiations.

Rod and cone opsin families differ in spectral tuning domains but not signal transducing domains as judged by saturated evolutionary trace analysis.

The visual receptor of rods and cones is a covalent complex of the apoprotein, opsin, and the light-sensitive chromophore, 11-cis-retinal. This pigment must fulfill many functions including photoactivation, spectral tuning, signal transmission, inactivation, and chromophore regeneration. Rod and cone photoreceptors employ distinct families of opsins. Although it is well known that these opsin families provide unique ranges in spectral sensitivity, it is unclear whether the families have additional functional differences. In this study, we use evolutionary trace (ET) analysis of 188 vertebrate opsin sequences to identify functionally important sites in each opsin family. We demonstrate the following results. (1) The available vertebrate opsin sequences produce a definitive description of all five vertebrate opsin families. This is the first demonstration of sequence saturation prior to ET analysis, which we term saturated ET (SET). (2) The cone opsin classes have class-specific sites compared to the rod opsin class. These sites reside in the transmembrane region and tune the spectral sensitivity of each opsin class to its characteristic wavelength range. (3) The cytoplasmic loops, primarily responsible for signal transmission and inactivation, are essentially invariant in rod versus cone opsins. This indicates that the electrophysiological differences between rod and cone photoreceptors cannot be ascribed to differences in the protein interaction regions of the opsins. SET shows that chromophore binding and regeneration are the only aspects of opsin structure likely to have functionally significant differences between rods and cones, whereas excitatory and adaptational properties of the opsin families appear to be functionally invariant.

Adaptive molecular evolution in the opsin genes of rapidly speciating cichlid species.

Cichlid fish inhabit a diverse range of environments that vary in the spectral content of light available for vision. These differences should result in adaptive selective pressure on the genes involved in visual sensitivity, the opsin genes. This study examines the evidence for differential adaptive molecular evolution in East African cichlid opsin genes due to gross differences in environmental light conditions. First, we characterize the selective regime experienced by cichlid opsin genes using a likelihood ratio test format, comparing likelihood models with different constraints on the relative rates of amino acid substitution, across sites. Second, we compare turbid and clear lineages to determine if there is evidence of differences in relative rates of substitution. Third, we present evidence of functional diversification and its relationship to the photic environment among cichlid opsin genes. We report statistical evidence of positive selection in all cichlid opsin genes, except short wavelength-sensitive 1 and short wavelength-sensitive 2b. In all genes predicted to be under positive selection, except short wavelength-sensitive 2a, we find differences in selective pressure between turbid and clear lineages. Potential spectral tuning sites are variable among all cichlid opsin genes; however, patterns of substitution consistent with photic environment-driven evolution of opsin genes are observed only for short wavelength-sensitive 1 opsin genes. This study identifies a number of promising candidate-tuning sites for future study by site-directed mutagenesis. This work also begins to demonstrate the molecular evolutionary dynamics of cichlid visual sensitivity and its relationship to the photic environment.