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Generation of Maternal Mutants Using zpc:cas9 Knock-in Zebrafish
Published on: July 22, 2025
Extraordinary molecular evolution in the PRDM9 fertility gene
James H Thomas1, Ryan O Emerson, Jay Shendure
1Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America. jht@u.washington.edu
Plos One
|December 31, 2009
Summary
The PRDM9 gene
Area of Science:
- Genetics and Evolutionary Biology
- Molecular Biology
- Reproductive Biology
Background:
- Allelic incompatibility in the mouse PRDM9 (Meisetz) gene contributes to hybrid male sterility and speciation.
- PRDM9 knockouts exhibit a meiosis I block, causing sterility in both sexes.
- PRDM9 encodes a protein with histone H3(K4) trimethyltransferase activity, a KRAB domain, and C2H2 zinc finger (ZF) DNA-binding domains.
Purpose of the Study:
- Analyze human coding polymorphism and interspecies evolutionary changes in the PRDM9 gene.
- Investigate the role of PRDM9 in genetic isolation and speciation.
- Re-evaluate the function of PRDM9 based on its molecular evolution.
Main Methods:
- Analysis of human coding polymorphism in PRDM9.
- Interspecies evolutionary analysis of the PRDM9 gene, focusing on ZF domains.
- Examination of positive selection and recombination patterns within PRDM9 ZF domains.
Main Results:
- PRDM9 ZF domains evolve rapidly, showing evidence of positive selection in primates.
- Positively selected amino acids in ZF domains are involved in nucleotide-specific contacts.
- Human PRDM9 exhibits high polymorphism in ZF domains, affecting nucleotide contact residues.
- Interfinger recombination homogenizes ZF domain sequences within species.
Conclusions:
- PRDM9 undergoes recurrent selection to alter its DNA-binding specificity.
- The rapid evolution of PRDM9 suggests a role beyond inducing meiosis-specific genes.
- PRDM9 may be involved in centromere segregation conflict, driven by evolving centromeric DNA.
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