Phenotype Gap Research Articles

Reconciling continuous and discrete models of C4 and CAM evolution.

A current argument in the CAM biology literature has focused on the nature of the CAM evolutionary trajectory: whether there is a smooth continuum of phenotypes between plants with C3 and CAM photosynthesis or whether there are discrete steps of phenotypic evolutionary change such as has been modelled for the evolution of C4 photosynthesis. A further implication is that a smooth continuum would increase the evolvability of CAM, whereas discrete changes would make the evolutionary transition from C3 to CAM more difficult. In this essay, I attempt to reconcile these two viewpoints, because I think in many ways this is a false dichotomy that is constraining progress in understanding how both CAM and C4 evolved. In reality, the phenotypic space connecting C3 species and strong CAM/C4 species is both a continuum of variably expressed quantitative traits and yet also contains certain combinations of traits that we are able to identify as discrete, recognizable phenotypes. In this sense, the evolutionary mechanics of CAM origination are no different from those of C4 photosynthesis, nor from the evolution of any other complex trait assemblage. To make progress, we must embrace the concept of discrete phenotypic phases of CAM evolution, because their delineation will force us to articulate what aspects of phenotypic variation we think are significant. There are some current phenotypic gaps that are limiting our ability to build a complete CAM evolutionary model: the first is how a rudimentary CAM biochemical cycle becomes established, and the second is how the 'accessory' CAM cycle in C3+CAM plants is recruited into a primary metabolism. The connections to the C3 phenotype we are looking for are potentially found in the behaviour of C3 plants when undergoing physiological stress - behaviour that, strangely enough, remains essentially unexplored in this context.

Applied Genetics and Plant Breeding in 21st Century for Crop Improvement – Status and Prospects

The foundation for molecular plant breeding is an interdisciplinary science that has revolutionized the 21st century with incorporation of genomic research, biotechnology and molecular marker applications with conventional plant breeding practices. To meet the food demand of the ever-increasing population of the 21st century, conventional breeding methods like ideotype breeding, participatory plant breeding with combination of recent breeding approaches like Genetically Modified crops, Marker Assisted Selection, Next Generation Sequencing play a demanding role. Co-operation among farmers, plant breeders, researchers should exist to develop quality crops with increased nutritional value. The challenge to feed the ever-increasing population can be met by integrating different research disciplines and activities that form the core of molecular plant breeding. Success of genomics depends on the ability to improve crop phenotypes and reduce the phenotype gap which will be a major concern of the 21st century.

Unlocking the Memory Component of Alzheimer's Disease: Biological Processes and Pathways across Brain Regions.

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory and a general cognitive decline leading to dementia. AD is characterized by changes in the behavior of the genome and can be traced across multiple brain regions and cell types. It is mainly associated with β-amyloid deposits and tau protein misfolding, leading to neurofibrillary tangles. In recent years, however, research has shown that there is a high complexity of mechanisms involved in AD neurophysiology and functional decline enabling its diverse presentation and allowing more questions to arise. In this study, we present a computational approach to facilitate brain region-specific analysis of genes and biological processes involved in the memory process in AD. Utilizing current genetic knowledge we provide a gene set of 265 memory-associated genes in AD, combinations of which can be found co-expressed in 11 different brain regions along with their functional role. The identified genes participate in a spectrum of biological processes ranging from structural and neuronal communication to epigenetic alterations and immune system responses. These findings provide new insights into the molecular background of AD and can be used to bridge the genotype–phenotype gap and allow for new therapeutic hypotheses.

Perspectives and recent progress of genome-wide association studies (GWAS) in fruits.

Earlier next-generation sequencing technologies are being vastly used to explore, administer, and investigate the gene space with accurate profiling of nucleotide variations in the germplasm. OVERVIEW ANDPROGRESS: Recently, novel advancements in high-throughput sequencing technologies allow a genotyping-by-sequencing approach that has opened up new horizons for extensive genotyping exploiting single-nucleotide-polymorphisms (SNPs). This method acts as a bridge to support and minimize a genotype to phenotype gap allowing genetic selection at the genome-wide level, named genomic selection that could facilitate the selection of traits also in the pomology sector. In addition to this, genome-wide genotyping is a prerequisite for genome-wide association studies that have been used successfully to discover the genes, which control polygenic traits including the genetic loci, associated with the trait of interest in fruit crops. This review article emphasizes the role of genome-wide approaches to unlock and explore the genetic potential along with the detection of SNPs affecting the phenotype of fruit crops and highlights the prospects of genome-wide association studies in fruits.

Heat stress and cowpea: genetics, breeding and modern tools for improving genetic gains

High-temperature stress is an important abiotic stress that significantly affects the growth and yield of agriculture crops, including cowpea, and is thus a great concern for global food security. Harnessing variability in crop germplasm through various breeding techniques could be a viable option for improving tolerance to various abiotic stresses, including heat stress. Classical breeding approaches have been used to determine the genetics of heat tolerance in cowpea. However, progress has been hampered as heat tolerance is governed by multiple genes and is highly influenced by G × E effects. During the last decade, the increase in cowpea genomic resources has played a key role in elucidating the QTLs controlling heat stress tolerance. Advances in transcriptome resources have also uncovered plausible candidate gene(s) in response to heat tolerance. Likewise, proteomic and metabolomic approaches have offered novel insights into the response of various heat shock and other related proteins and metabolites involved in heat stress tolerance. Most importantly, increasing the precision of phenotyping approaches would enable us to close the genotype–phenotype gap to better understand the heat tolerance response in cowpea. Next-generation breeding techniques, such as MAGIC, genomic selection, speed breeding, and genome editing tools, have the potential to accelerate the creation of heat-tolerant cowpea genotypes.

Bridging the genotype-phenotype gap for a Mediterranean pine by semi-automatic crown identification and multispectral imagery.

Progress in high-throughput phenotyping and genomics provides the potential to understand the genetic basis of plant functional differentiation. We developed a semi-automatic methodology based on unmanned aerial vehicle (UAV) imagery for deriving tree-level phenotypes followed by genome-wide association study (GWAS). An RGB-based point cloud was used for tree crown identification in a common garden of Pinus halepensis in Spain. Crowns were combined with multispectral and thermal orthomosaics to retrieve growth traits, vegetation indices and canopy temperature. Thereafter, GWAS was performed to analyse the association between phenotypes and genomic variation at 235 single nucleotide polymorphisms (SNPs). Growth traits were associated with 12 SNPs involved in cellulose and carbohydrate metabolism. Indices related to transpiration and leaf water content were associated with six SNPs involved in stomata dynamics. Indices related to leaf pigments and leaf area were associated with 11 SNPs involved in signalling and peroxisome metabolism. About 16-20% of trait variance was explained by combinations of several SNPs, indicating polygenic control of morpho-physiological traits. Despite a limited availability of markers and individuals, this study is provides a successful proof-of-concept for the combination of high-throughput UAV-based phenotyping with cost-effective genotyping to disentangle the genetic architecture of phenotypic variation in a widespread conifer.

Upregulation of Hallmark Muscle Genes Protects GneM743T/M743T Mutated Knock-In Mice From Kidney and Muscle Phenotype.

Background:Mutations in GNE cause a recessive, adult onset myopathy characterized by slowly progressive distal and proximal muscle weakness. Knock-in mice carrying the most frequent mutation in GNE myopathy patients, GneM743T/M743T, usually die few days after birth from severe renal failure, with no muscle phenotype. However, a spontaneous sub-colony remains healthy throughout a normal lifespan without any kidney or muscle pathology.Objective:We attempted to decipher the molecular mechanisms behind these phenotypic differences and to determine the mechanisms preventing the kidney and muscles from disease.Methods:We analyzed the transcriptome and proteome of kidneys and muscles of sick and healthy GneM743T/M743T mice.Results:The sick GneM743T/M743T kidney was characterized by up-regulation of extra-cellular matrix degradation related processes and by down-regulation of oxidative phosphorylation and respiratory electron chain pathway, that was also observed in the asymptomatic muscles. Surprisingly, the healthy kidneys of the GneM743T/M743T mice were characterized by up-regulation of hallmark muscle genes. In addition the asymptomatic muscles of the sick GneM743T/M743T mice showed upregulation of transcription and translation processes.Conclusions:Overexpression of muscle physiology genes in healthy GneM743T/M743T mice seems to define the protecting mechanism in these mice. Furthermore, the strong involvement of muscle related genes in kidney may bridge the apparent phenotypic gap between GNE myopathy and the knock-in GneM743T/M743T mouse model and provide new directions in the study of GNE function in health and disease.

Closing the 'phenotype gap' in precision medicine: improving what we measure to understand complex disease mechanisms.

The central concept underlying precision medicine is a mechanistic understanding of each disease and its response to therapy sufficient to direct a specific intervention. To execute on this vision requires parsing incompletely defined disease syndromes into discrete mechanistic subsets and developing interventions to precisely address each of these etiologically distinct entities. This willrequire substantial adjustment of traditional paradigms which have tended to aggregate high-level phenotypes with very different etiologies. In the currentenvironment, where diagnoses are not mechanistic, drug development has become so expensive that it is now impractical to imagine the cost-effective creation of new interventions for many prevalent chronic conditions. The vision of precision medicine also argues for a much more seamless integration of research and development with clinical care, where shared taxonomies willenable every clinical interaction to inform our collective understanding of disease mechanisms and drug responses. Ideally, this would be executed in ways that drive real-time and real-world discovery, innovation, translation, and implementation. Only in oncology, where at least some of the biology is accessible through surgical excision of the diseased tissueor liquid biopsy, has "co-clinical" modeling proven feasible. In most common germline disorders, while genetics often reveal the causal mutations, there still remain substantial barriers to efficient disease modeling. Aggregation of similar disorders under single diagnostic labelshas directly contributed to the paucity of etiologic and mechanistic understanding by directlyreducing the resolution of any subsequent studies. Existing clinical phenotypes are typically anatomic, physiologic, or histologic, and result in a substantial mismatch in information content between the phenomes in humans or in animal 'models' and the variation in the genome. This lack of one-to-one mapping of discrete mechanisms between disease and animalmodels causes a failure of translation and is one form of 'phenotype gap.' In this review, we will focus on the origins of the phenotyping deficit and approaches that may be considered to bridge the gap, creating shared taxonomies between human diseases and relevant models, using cardiovascular examples.

Physiological and Developmental Response of Selected Upland Rice Genotypes to Water and Nutrient Stress Condition

Drought is a major challenge for all agricultural crops, but for rice, it is even more serious, because of its semi aquatic phylogenetic origins and the diversity of rice ecosystems and growing conditions. The most important source of climate-related risks for rice production in rain-fed areas is drought.Crop physiology has made a significant contribution to understanding the mechanisms underlying crop growth and development, and bridging the “phenotype gap” generated by the recent progress in genomics. The study aimed to determine growth and physiological response of IRAT 109 and Lemont to water deficit and fertilizer application. Plants were subjected to water nutrient stress treatment in the field. Water and fertilizer treatment were initiated at 42 days after sowing (das). Fertilizer treatment was applied at 60 Kgha-1N and 60 Kgha-1N+45 Kgha-1P. Morphological and physiological measurements were done at 21, 42, 63 and 84th das. Root sampling done during the periods, at depths of 0-10 cm, 10-20 cm, and 20-40 Cm. The soil moisture content had a significant effect and decreased with increasing water deficit. The plant height, plant biomass both shoots and root reduced with decreasing water content and nutrient load in the soil. Lemont was significantly affected and registered lower values for various growth indices compared to IRAT 109. The was significant reduction in yields between the two rice cultivars under drought stress condition, though IRAT 109 exhibited relatively higher yield index under drought stress condition, the improved performance could be attributed to its ability to escape drought stress due to its early maturing ability. Fertilizer application has a significant effect on yield and yield component in rice, thus the proper fertilizer application is a key in achieving good yield in rice production. The finding of this research will help farmers in adopting high precision fertilizer application to ensure a good yield. In addition, rice breeders can utilize IRAT109 in developing more resilient and highly adaptive rice cultivars.

Global evolution of glycosylated polyene macrolide antibiotic biosynthesis

Antibiotics are the most marvelous evolutionary products of microbes to obtain competitive advantage and maintain ecological balance. However, the origination and development of antibiotics has yet to be explicitly investigated. Due to diverse structures and similar biosynthesis, glycosylated polyene macrolides (gPEMs) were chosen to explore antibiotic evolution. A total of 130 candidate and 38 transitional gPEM clusters were collected from actinomycetes genomes, providing abundant references for phenotypic gaps in gPEM evolution. The most conserved parts of gPEM biosynthesis were found and used for phylogeny construction. On this basis, we proposed ancestral gPEM clusters at different evolutionary stages and interpreted the possible evolutionary histories in detail. The results revealed that gPEMs evolved from small rings to large rings and continuously increased structural diversity through acquiring, discarding and exchanging genes from different evolutionary origins, as well as co-evolution of functionally related proteins. The combination of horizontal gene transfers, environmental effects and host preference resulted in the diversity and worldwide distribution of gPEMs. This study is not only a useful exploration on antibiotic evolution but also an inspiration for diversity and biogeographic investigations on antibiotics in the era of Big Data.

Accessing the Phenotype Gap: Enabling Systematic Investigation of Paralog Functional Complexity with CRISPR

Single-gene knockout experiments can fail to reveal function in the context of redundancy, which is frequently observed among duplicated genes (paralogs) with overlapping functions. We discuss the complexity associated with studying paralogs and outline how recent advances in CRISPR will help address the "phenotype gap" and impact biomedical research.

On the role of host phenotypic plasticity in host shifting by parasites.

Ecological speciation appears to contribute to the diversification of insect herbivores and other parasites, which together comprise a major component of Earth's biodiversity. Host shifts are likely an important step in ecological speciation, and understanding how such shifts occur is critical to forming and testing hypotheses explaining parasite diversity. In this article, I argue that phenotypic variation in hosts arising from environmental variation (phenotypic plasticity) can promote shifts in parasites by bridging both spatiotemporal and phenotypic gaps between ancestral and novel hosts. This hypothesis, which I call the 'plastic-bridge hypothesis', is conceptually distinct from those invoking genetic variation in bridging these gaps. I describe the mechanistic basis of plastic bridges, review circumstantial evidence in support of the hypothesis and suggest strategies for testing it. I use herbivorous insects and their host plants as a model, but the proposed ideas apply to any system fitting a broad definition of a host-parasite relationship. The plastic-bridge perspective suggests that parasite diversity is not only due to divergent selection provided by hosts, but also to the intraspecific variation that facilitates shifts between them. This view is timely, as biological invasion and range shifts associated with climate change foster novel interactions between parasites and hosts.

Dissecting the phenotypic components of crop plant growth and drought responses based on high-throughput image analysis.

Significantly improved crop varieties are urgently needed to feed the rapidly growing human population under changing climates. While genome sequence information and excellent genomic tools are in place for major crop species, the systematic quantification of phenotypic traits or components thereof in a high-throughput fashion remains an enormous challenge. In order to help bridge the genotype to phenotype gap, we developed a comprehensive framework for high-throughput phenotype data analysis in plants, which enables the extraction of an extensive list of phenotypic traits from nondestructive plant imaging over time. As a proof of concept, we investigated the phenotypic components of the drought responses of 18 different barley (Hordeum vulgare) cultivars during vegetative growth. We analyzed dynamic properties of trait expression over growth time based on 54 representative phenotypic features. The data are highly valuable to understand plant development and to further quantify growth and crop performance features. We tested various growth models to predict plant biomass accumulation and identified several relevant parameters that support biological interpretation of plant growth and stress tolerance. These image-based traits and model-derived parameters are promising for subsequent genetic mapping to uncover the genetic basis of complex agronomic traits. Taken together, we anticipate that the analytical framework and analysis results presented here will be useful to advance our views of phenotypic trait components underlying plant development and their responses to environmental cues.

Closing the genotype-phenotype gap: emerging technologies for evolutionary genetics in ecological model vertebrate systems.

The analysis of genetic and epigenetic mechanisms of the genotype-phenotypic connection has, so far, only been possible in a handful of genetic model systems. Recent technological advances, including next-generation sequencing methods such as RNA-seq, ChIP-seq and RAD-seq, and genome-editing approaches including CRISPR-Cas, now permit to address these fundamental questions of biology also in organisms that have been studied in their natural habitats. We provide an overview of the benefits and drawbacks of these novel techniques and experimental approaches that can now be applied to ecological and evolutionary vertebrate models such as sticklebacks and cichlid fish. We can anticipate that these new methods will increase the understanding of the genetic and epigenetic factors influencing adaptations and phenotypic variation in ecological settings. These new arrows in the methodological quiver of ecologist will drastically increase the understanding of the genetic basis of adaptive traits - leading to a further closing of the genotype-phenotype gap.

An Expression QTL of Closely Linked Candidate Genes Affects pH of Meat in Chickens

Genetical genomics has been suggested as a powerful approach to study the genotype-phenotype gap. However, the relatively low power of these experiments (usually related to the high cost) has hindered fulfillment of its promise, especially for loci (QTL) of moderate effects.One strategy with which to overcome the issue is to use a targeted approach. It has two clear advantages: (i) it reduces the problem to a simple comparison between different genotypic groups at the QTL and (ii) it is a good starting point from which to investigate downstream effects of the QTL. In this study, from 698 F2 birds used for QTL mapping, gene expression profiles of 24 birds with divergent homozygous QTL genotypes were investigated. The targeted QTL was on chromosome 1 and affected initial pH of breast muscle. The biological mechanisms controlling this trait can be similar to those affecting malignant hyperthermia or muscle fatigue in humans. The gene expression study identified 10 strong local signals that were markedly more significant compared to any genes on the rest of the genome. The differentially expressed genes all mapped to a region <1 Mb, suggesting a remarkable reduction of the QTL interval. These results, combined with analysis of downstream effect of the QTL using gene network analysis, suggest that the QTL is controlling pH by governing oxidative stress. The results were reproducible with use of as few as four microarrays on pooled samples (with lower significance level). The results demonstrate that this cost-effective approach is promising for characterization of QTL.

Bridging the genotype–phenotype gap: what does it take?

The genotype–phenotype map (GP map) concept applies to any time point in the ontogeny of a living system. It is the outcome of very complex dynamics that include environmental effects, and bridging the genotype–phenotype gap is synonymous with understanding these dynamics. The context for this understanding is physiology, and the disciplinary goals of physiology do indeed demand the physiological community to seek this understanding. We claim that this task is beyond reach without use of mathematical models that bind together genetic and phenotypic data in a causally cohesive way. We provide illustrations of such causally cohesive genotype–phenotype models where the phenotypes span from gene expression profiles to development of whole organs. Bridging the genotype–phenotype gap also demands that large-scale biological (‘omics’) data and associated bioinformatics resources be more effectively integrated with computational physiology than is currently the case. A third major element is the need for developing a phenomics technology way beyond current state of the art, and we advocate the establishment of a Human Phenome Programme solidly grounded on biophysically based mathematical descriptions of human physiology.

Genome-wide association mapping of leaf metabolic profiles for dissecting complex traits in maize

The diversity of metabolites found in plants is by far greater than in most other organisms. Metabolic profiling techniques, which measure many of these compounds simultaneously, enabled investigating the regulation of metabolic networks and proved to be useful for predicting important agronomic traits. However, little is known about the genetic basis of metabolites in crops such as maize. Here, a set of 289 diverse maize inbred lines was genotyped with 56,110 SNPs and assayed for 118 biochemical compounds in the leaves of young plants, as well as for agronomic traits of mature plants in field trials. Metabolite concentrations had on average a repeatability of 0.73 and showed a correlation pattern that largely reflected their functional grouping. Genome-wide association mapping with correction for population structure and cryptic relatedness identified for 26 distinct metabolites strong associations with SNPs, explaining up to 32.0% of the observed genetic variance. On nine chromosomes, we detected 15 distinct SNP-metabolite associations, each of which explained more then 15% of the genetic variance. For lignin precursors, including p-coumaric acid and caffeic acid, we found strong associations (P values to ) with a region on chromosome 9 harboring cinnamoyl-CoA reductase, a key enzyme in monolignol synthesis and a target for improving the quality of lignocellulosic biomass by genetic engineering approaches. Moreover, lignin precursors correlated significantly with lignin content, plant height, and dry matter yield, suggesting that metabolites represent promising connecting links for narrowing the genotype-phenotype gap of complex agronomic traits.

The Importance of Being Specified: Cell Fate Decisions and Their Role in Cell Biology

The Importance of Being Specified: Cell Fate Decisions and Their Role in Cell Biology

Standardized Phenotyping: Advantages to Horticulture—Introduction to the Workshop

New and emerging DNA sequencing technologies have recently accelerated the pace of gene discovery. Phenotypes are the expression of genotypes and reveal gene function. As such, phenotypes provide the crucial link between sequence variation and biological function. As a result of the relative ease in obtaining vast quantities of genomic data, phenotypic information is not keeping pace with the explosion in available genomic information. The lack of reliable and available phenotypic data may limit the use of statistical methods to identify the associations between phenotypic and genotypic (or genomic) data, thus hindering our understanding of the genetic basis of biological processes. Sequence data reveal high levels of genomic syntenies that suggest conservation of gene order, content, and function among phylogenetically related groups. Although it is possible to assign putative gene function based on reported function in other plants and, in some instances, other organisms, inferences should be validated by experimental genetic analysis. Only approximately two-thirds of genes have an assigned biochemical function and a small percentage of these genes are associated with a phenotype (Bochner, 2003). This ‘‘phenotype gap,’’ first described in mouse research (Brown and Peters, 1996), is a major challenge in biological understanding of plant processes and translational genomics. This gap must be filled by developing a coordinated effort to standardize phenotyping protocols across personnel, seasons, regions, and institutions and apply uniform phenotypic nomenclature to facilitate database searches, comparisons, and extrapolations. Standardized phenotypic protocols are the prerequisite for the production of a so-called ‘‘phenomic map’’ in which every identified gene is defined by at least one phenotype. Such a system of comparative phenomics would facilitate the progression of knowledge throughout model biological systems in plants and from other well-studied organisms. As research projects become more nationally and internationally integrated, the need for standardized data collection and documentation has grown. We highlight several projects and germplasm centers that have recognized the need for developing standardized phenotyping protocols and the associated nomenclature, annotation, and databases for enabling comparative phenomics. This workshop on standardized phenotyping and the advantages it provides for horticultural crops was held at the 2009 American Society for Horticultural Science Annual Conference in St. Louis, MO, and was organized by the Genetics and Germplasm Working Group. The objectives of the workshop were to 1) describe phenotyping efforts in diverse horticultural disciplines; 2) relate advantages for using standardized phenotyping for broad applicability in research and breeding programs; 3) emphasize the importance of standardization for genomics applications; and 4) give an update on standardized ontology for horticultural crops. Each of the five presentations was recorded and has been made available at http://www.ashs.org/db/horttalks/ listing2.lasso. The five presentations include examples, advantages, constraints, and recommendations of/for the use standardized phenotyping in horticulture. The first speaker, Joseph Postman, related how ‘‘Standardized plant disease evaluations will enhance resistance gene discovery.’’ He emphasized the value of using standardized numerical ratings and reference cultivars to record resistant and tolerant individuals. Jay Scott in ‘‘Phenotyping of tomato for SolCAP and onward into the void’’ and Jim Luby (for Cameron Peace and coworkers) in ‘‘Standardized phenotyping of apple texture for improved breeding and research efficiency’’ spoke of ongoing funded research programs in Solanaceae and Rosaceae, respectively, that have sought to use standardized recording methods across laboratories and locations to document germplasm performance. David Rudell presented ‘‘Standardized postharvest quality and biochemical phenotyping for precise population comparison’’ and described the value of standardization when documenting postharvest quality attributes in fruit in a quantitative manner. Gayle Volk concluded the workshop with a presentation ‘‘Advantages for the use of standardized phenotyping in the National Plant Germplasm System’’ that stressed the advantages and benefits for programs that overcome the difficulties involved in standardization, including examples from both the mammalian and plant systems. Postman, Scott, Rudell, and Volk have prepared manuscripts to document their American Society for Horticultural Science Workshop presentations.

The genetic basis of recessive self-colour pattern in a wild sheep population

Bridging the genotype-phenotype gap for traits of ecological and evolutionary importance in natural populations can provide a novel insight into the origin and maintenance of variation. Here, we identify the gene and putative causal mutations underlying a recessive colour pattern phenotype ('self' or uniform colour) in a wild population of primitive Soay sheep. We targeted the agouti signalling protein (ASIP) gene, a positional candidate based on previous study that mapped the Coat pattern locus to a presumptive region on chromosome 13. We found evidence for three recessive mutations, including two functional changes in the coding sequence and a putative third cis-regulatory mutation that inactivates the promoter. These mutations define up to five haplotypes in Soays, which collectively explained the coat pattern in all but one member of a complex multi-generational pedigree containing 621 genotyped individuals. The functional mutations are in strong linkage disequilibrium in the study population, and are identical to those known to underlie the self phenotype in domestic sheep. This is indicative of a recent (and simultaneous) origin in Soay sheep, possibly as a consequence of past interbreeding with modern domestic breeds. This is only the second study in which ASIP has been linked to variation in pigmentation in a natural population. Knowledge of the genetic basis of self-colour pattern in Soay sheep, and the recognition that several mutations are segregating in the population, will aid future studies investigating the role of selection in the maintenance of the polymorphism.