Document Type

Article

Publication Date

6-2012

Keywords

Prenylation, Human disease, Fertility, Molecular evolution, Mutagenesis

Abstract

Many proteins require the addition of a hydrophobic prenyl anchor (prenylation) for proper trafficking and localization in the cell. Prenyl proteases play critical roles in modifying proteins for membrane anchorage. The type I prenyl protease has a defined function in yeast (Ste24p/Afc1p) where it modifies a mating pheromone, and in humans (Zmpste24) where it has been implicated in a disease of premature aging. Despite these apparently very different biological processes, the type I prenyl protease gene is highly conserved, encoded by a single gene in a wide range of animal and plant groups. A notable exception is Drosophila melanogaster, where the gene encoding the type I prenyl protease has undergone an unprecedented series of duplications in the genome, resulting in five distinct paralogs, three of which are organized in a tandem array, and demonstrate high conservation, particularly in the vicinity of the active site of the enzyme. We have undertaken targeted deletion to remove the three tandem paralogs from the genome. The result is a male fertility defect, manifesting late in spermatogenesis. Our results also show that the ancestral type I prenyl protease gene in Drosophila is under strong purifying selection, while the more recent replicates are evolving rapidly. Our rescue data support a role for the rapidly evolving tandem paralogs in the male germline. We propose that potential targets for the male-specific type I prenyl proteases include proteins involved in the very dramatic cytoskeletal remodeling events required for spermatid maturation.

Publication Title

G3: Genes, Genomes, Genetics

Volume

2

Required Publisher's Statement

Copyright © 2012 Adolphsen et al. doi: 10.1534/g3.112.002188

Comments

Supporting information is available online at http://www.g3journal.org/lookup/ suppl/doi:10.1534/g3.112.002188/-/DC1 1

Subjects - Topical (LCSH)

Genetics, Experimental; Proteolytic enzymes; Drosophila melanogaster; Germ cells

Genre/Form

articles

Type

Text

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Language

English

Format

application/pdf

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Biology Commons

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