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Updated: Jun 17, 2025
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Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
Published on: January 2, 2018
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The GC-content at the 5' ends of human protein-coding genes is undergoing mutational decay
Yi Qiu1, Yoon Mo Kang1, Christopher Korfmann2
1Department of Biochemistry, University of Toronto, Toronto, Ontario, M5G1M1, Canada.
Genome Biology
|August 13, 2024
Summary
GC-rich gene regions near transcriptional start sites (TSSs) in vertebrates are shaped by recombination patterns. In species with recombination away from TSSs, GC-content decays, suggesting selection is not maintaining these peaks.
Area of Science:
- Genomics
- Evolutionary Biology
- Molecular Biology
Background:
- Most vertebrate protein-coding genes exhibit a GC-content peak near the 5' transcriptional start site (TSS).
- This GC-rich feature is crucial for efficient mRNA nuclear export and translation.
- The evolutionary origins and maintenance mechanisms of TSS GC-peaks remain largely unknown.
Purpose of the Study:
- To investigate the evolutionary forces driving GC-content dynamics at gene TSSs.
- To analyze the role of recombination and mutation in shaping GC-peaks across vertebrate species.
Main Methods:
- Comparative genomic analysis of nucleotide substitution rates across species.
- Examination of human de novo mutations.
- Analysis of GC-content patterns in relation to recombination rates and the PRDM9 gene.
Main Results:
- GC-peaks at TSSs were likely present in the common ancestor of vertebrates and amniotes.
- In apes and rodents (PRDM9-mediated recombination away from TSSs), GC-content at the 5' end of genes is decaying.
- In canids (recombination at TSSs, lacking PRDM9), 5' gene GC-content is increasing, impacting synonymous codon usage.
Conclusions:
- GC-peak dynamics in amniotes are significantly influenced by historical recombination patterns.
- The observed GC-content decrease in apes and rodents suggests the GC-peak is not actively maintained by selection on most protein-coding genes in these lineages.
- Mutational decay towards equilibrium is the default for non-functional DNA.
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