Phenoscape use cases

Identify candidate genes for a particular evolutionary phenotype

Motivation

One focus of developmental biology is to understand how genes regulate development, and therefore examining the phenotypic effects of single gene mutations is a major emphasis in studies of zebrafish and other model organisms. Genetic change underlies alterations in evolutionary characters as well, but the connection between specific genes and most evolutionary changes has not been made. Thus, one of the first steps in investigating the developmental basis for a particular evolutionary change in morphology is to hypothesize a relationship between that morphology and a set of candidate genes.

Example

Extensive variation in the size, shape, presence and absence of bones characterizes the course of vertebrate evolution, and such variation is commonly used in phylogenetic analysis in fishes. An evolutionary biologist observes variation in the size of a particular bone, ceratobranchial 5, among Ostariophysi (Siebert, '87). The person queries the evolutionary phenotype database for matching mutant zebrafish phenotypes by using terms from shared ontologies: Entity = Ceratobranchial 5 [from TAO] and all qualities pertaining to attribute ‘size’ [from the PATO]. The response will be a list of zebrafish mutants and their phenotypes, along with the associated genes, and possibly gene expression images. sox9a is shown to have a role in size reduction in ceratobranchial 5 in the mutant line sox9ahi1134 (Yan et al., '05). The evolutionary biologist would hypothesize that the regulation or sequence of sox9a has been altered during evolution to result in the enlargement of this bone in two lineages, and they would pursue the appropriate developmental genetic work to test this hypothesis. They might further explore the function of the gene in other model organisms.

Input

A phenotype search specification: entity, quality, etc. Option to match exactly or to match descendant terms (as in quality "size", above).

Output

A list of ZFIN mutant identifiers with matching phenotype of each, associated gene, perhaps gene expression images (or links to).

Identify evolutionary changes that match the phenotype of a zebrafish mutant

Motivation

With the rise of evo-devo, developmental biologists have become more interested in exploring the co- variation of developmental and evolutionary traits. A common question is simply whether a particular trait varies in evolution and if so, what the pattern of evolution has been.

Example

A developmental biologist observes a reduction in number of branchiostegal rays (bones in the gill membrane) in a zebrafish mutant due to changes in endothelin-1. The user wants to know whether branchiostegal ray number is variable among fish species, and if so, they want to see the pattern of change across fish evolution. They query the evolutionary phenotype database using terms from shared ontologies: Entity = Branchiostegal rays [from TAO] and all qualities pertaining to attribute ‘count’ [from the PATO]. The response will be a list of taxa and their matching evolutionary character changes or states. The user would see that all cypriniforms, including zebrafish, have three branchiostegal rays, but other fishes, including close ostariophysan relatives, have higher and lower numbers (McAllister, '68).

Input

A phenotype search specification: entity, quality, etc. Option to match exactly or to match descendant terms (as in quality "count", above).

Output

A list of matching evolutionary phenotypes and the taxon for each.

Compare genetically and evolutionarily correlated characters

Motivation

Determining whether morphological characters are independent or genetically/developmentally correlated has been a long- standing and intractable question in phylogenetic systematics (Sneath and Sokal, '73; Wiley, '81; Farris, '83; O'Keefe and Wagner, '01). Often the correlation between two (or more) characters is difficult to ascertain, particularly when the characters involved are linked together at the molecular level. However, if evolutionary character changes could be matched to mutant developmental and morphological phenotypes, single-gene mutant phenotype data from zebrafish would allow a detailed analysis of this issue for any evolutionary characters of interest.

Example

On a phylogenetic tree of the Ostariophysi, an evolutionary biologist observes a suite of the characters that support the monophyly of a particular clade. These characters, however, are all marked by changes in size of the dentary, maxilla, ceratohyal, and opercle bones. The user wants to know whether the size modification of each of these bones represents independent support for this phylogenetic hypothesis, or whether the changes are correlated due to a common genetic or developmental basis. Querying the zebrafish mutant phenotype descriptions in EQ syntax with the above anatomical terms would show that in sox9ahi1134 mutants, the dentary, opercle, and maxilla bones are reduced in size relative to wild-type zebrafish, whereas other bones are relatively unaffected (Yan et al., '05). This suggests that the size of the dentary, opercle, and maxilla might be co-regulated in part by sox9a, and we would conclude that support for the monophyly of this clade is not as strong as previously proposed.