We previously described paralogous human genes {NUDT10 and NUDT11 [where NUDT is (nucleoside diphosphate attached moiety ‘X’)-type motif, also known as the ‘nudix’-type motif]} encoding type 3 diphosphoinositol polyphosphate phosphohydrolases (DIPP3) [Hidaka, Caffrey, Hua, Zhang, Falck, Nickel, Carrel, Barnes and Shears (2002) J. Biol. Chem. 277, 32730–32738]. Normally, gene duplication is redundant, and lacks biological significance. Is this true for the DIPP3 genes? We address this question by characterizing highly-conserved murine Nudt10 and Nudt11 homologues of the human genes. Thus these genes must have been duplicated prior to the divergence of primates and sciurognath rodents, approx. 115 million years ago, greatly exceeding the 4 million year half-life for inactivation of redundant paralogues; our data therefore indicate that the DIPP3 duplication is unusual in being physiologically significant. One possible functional consequence is gene neofunctionalization, but we exclude that, since Nudt10 and Nudt11 encode identical proteins. Another possibility is gene subfunctionalization, which we studied by conducting the first quantitative expression analysis of these genes. We demonstrated high Nudt10 expression in liver, kidney and testis; Nudt11 expression is primarily restricted to the brain. This differential, but complementary, expression pattern indicates that subfunctionalization is the evolutionary consequence of DIPP3 gene duplication. Our kinetic data argue that diphosphoinositol polyphosphates are more physiologically relevant substrates for DIPP3 than are either diadenosine hexaphosphate or 5-phosphoribosyl 1-pyrophosphate. Thus the significance of the Nudt10/Nudt11 duplication is specific hydrolysis of diphosphoinositol polyphosphates in a tissue-dependent manner.
Skip Nav Destination
Article navigation
Research Article|
July 01 2003
Paralogous murine Nudt10 and Nudt11 genes have differential expression patterns but encode identical proteins that are physiologically competent diphosphoinositol polyphosphate phosphohydrolases
Len V. HUA;
Len V. HUA
∗Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, U.S.A.
Search for other works by this author on:
Kiyoshi HIDAKA;
Kiyoshi HIDAKA
∗Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, U.S.A.
Search for other works by this author on:
Xavier PESESSE;
Xavier PESESSE
∗Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, U.S.A.
Search for other works by this author on:
Larry D. BARNES;
Larry D. BARNES
†Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900, U.S.A.
Search for other works by this author on:
Stephen B. SHEARS
Stephen B. SHEARS
1
∗Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, U.S.A.
1To whom correspondence should be addressed (e-mail shears@niehs.nih.gov).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 20 2003
Revision Received:
April 01 2003
Accepted:
April 10 2003
Accepted Manuscript online:
April 10 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 373 (1): 81–89.
Article history
Received:
January 20 2003
Revision Received:
April 01 2003
Accepted:
April 10 2003
Accepted Manuscript online:
April 10 2003
Citation
Len V. HUA, Kiyoshi HIDAKA, Xavier PESESSE, Larry D. BARNES, Stephen B. SHEARS; Paralogous murine Nudt10 and Nudt11 genes have differential expression patterns but encode identical proteins that are physiologically competent diphosphoinositol polyphosphate phosphohydrolases. Biochem J 1 July 2003; 373 (1): 81–89. doi: https://doi.org/10.1042/bj20030142
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.