Paralogs can be defined as related genes within a genome that are thought to arise from gene duplication events. Because paralogous proteins share amino acid identity, they can have redundant functions. But the picture is not necessarily so straightforward. Indeed, there are examples in which paralogous genes have distinct functions in some tissues, and overlapping functions in others.
The DRSC/TRiP is engaged in a project in collaboration with the Perrimon and Bellen labs to generate resources useful for the study of paralogous genes in Drosophila.
Online Resources for Drosophila Paralogs:
One part of our project involved building a new online resource, Paralog Explorer, which helps researchers quickly identify paralogs of a given gene of interest, as well as relevant information such as in which tissues the paralogous genes are expressed.
You can also find paralogs using our popular DIOPT online resource by choosing the same species as the “input” and “output” species.
Fly Stock Resources for Studying Paralog Functions:
Another part of our project is to build transgenic flies that facilitate both orthologs in a paralog pair using CRISPR-Cas9 technology.
The resulting fly stocks will allow for tissue-specific control, such that the effect of making a tissue mosaic for knockout of both paralogs can be observed. A feature of our approach is that knockout by Cas9 is under the control of the Gal4-UAS system, such that either whole-animal or tissue-specific studies can be performed.
We expect the fly stock resource will help identify paralog pairs with redundant functions by uncovering phenotypes not observed when either gene alone is perturbed and provide a resource for study of more complex paralog relationships.
We are soliciting nominations from the community for paralog pairs for which we would build fly stocks that facilitate double-knockout via CRISPR-Cas9.
- Do you have a phenotypic assay with which you’d be interested to test the effects double-knockout of paralog pairs?
- Do you have reason to think that a pair of paralogs might have redundant or partially redundant functions in a given tissue of interest to you?
- Would you otherwise find the type of fly stocks we’re building useful in your project?
If so, then please nominate genes for the fly stock production pipeline! To submit a nomination, please go to this form. You will be asked to provide some basic information about yourself and your lab, the paralogous genes you’re interested in, and the assay or project.
Office of the Director R24 OD26435: "Using CRISPR technology to study the function of paralogous genes" (PI: N. Perrimon | Co-PI: H. Bellen | Co-I: S. Mohr)