Polymorphism of Polyglutamine Proteins in Candida glabrata and Role in Adaptation

Ref ID: 18801

Author:

T. D. Edlind, PhD (Doctor of Philosophy) – Professor, S. K. Katiyar, PhD – Research Associate Professor;

Author address:

Drexel Univ. Coll. of Med., Philadelphia, PA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: In humans, polymorphisms of polyglutamine (polyQ)-containing proteins, such as the transcription factor huntingtin, have been implicated in neurodegenerative disorders, notably Huntington Disease. The function and evolution of these polyQ regions is poorly understood. Intriguingly, polyQ-containing proteins are also common in fungi, including the opportunistic yeast Candida glabrata. Specifically, the three most significant hits identified by BLASTP (with Q20 as query) of database strain CBS138 were transcription factors/co-factors Tup1A (Q43), Ypr015c (Q28), and Gal11A (Q22, Q23). We hypothesized that their polyQ regions are polymorphic and enable C. glabrata to adapt to environmental changes, such as antifungal exposure, immune responses, and colonization of new tissue or host. Methods: To test this, DNA was prepared from 12 strains representing the major C. glabrata clades based on a CgTypeM (polymorphic intergenic region) phylogenetic tree; their polyQ-encoding regions were then amplified by PCR and sequenced. Results: Clustalw alignments confirmed that the polyQ regions of all three proteins were indeed polymorphic. Tup1A, a transcriptional co-repressor with multiple roles including stress response, was the most polymorphic, with polyQ regions ranging from Q27 to Q52. Importantly, comparisons between the phylogenetic trees based on CgTypeM and the three polyQ proteins revealed discordance; e.g., three genotypically matched strains demonstrated -3/-3/-3, +2/+2/-3, and -16/-16/-4 changes in the lengths of their Gal11A, Ypr015c, and Tup1 polyQ regions, respectively. Conclusions: These data suggest that the polyQ regions of Tup1A, Ypr015c, and Gal11A evolved independently, consistent with a role in adaptation.

Abstract Number: M-966

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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