A positive correlation between GC content and growth temperature in prokaryotes
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Abstract
Background: GC pairs are generally more stable than AT pairs; GC-rich genomes were proposed to be more adapted to high temperatures than AT-rich genomes. Previous studies consistently showed positive correlations between growth temperature and the GC contents of structural RNA genes. However, for the whole genome sequences and the silent sites of the codons in protein-coding genes, the relationship between GC content and growth temperature is in a long-lasting debate. Results: With a dataset much larger than previous studies (681 bacteria and 155 archaea with completely assembled genomes), our phylogenetic comparative analyses showed positive correlations between optimal growth temperature (Topt) and GC content both in bacterial and archaeal structural RNA genes and in bacterial whole genome sequences, chromosomal sequences, plasmid sequences, core genes, and accessory genes. However, in the 155 archaea, we did not observe a significant positive correlation of Topt with whole-genome GC content (GC w ) or GC content at four-fold degenerate sites. We randomly drew 155 samples from the 681 bacteria for 1000 rounds. In most cases (> 95%), the positive correlations between Topt and genomic GC contents became statistically nonsignificant ( P > 0.05). This result suggested that the small sample sizes might account for the lack of positive correlations between growth temperature and genomic GC content in the 155 archaea and the bacterial samples of previous studies. Comparing the GC content among four categories (psychrophiles/psychrotrophiles, mesophiles, thermophiles, and hyperthermophiles) also revealed a positive correlation between GC w and growth temperature in bacteria. By including the GC w of incompletely assembled genomes, we expanded the sample size of archaea to 303. Positive correlations between GC w and Topt appear especially after excluding the halophilic archaea whose GC contents might be strongly shaped by intense UV radiation. Conclusions: This study explains the previous contradictory observations and ends a long debate. Prokaryotes growing in high temperatures have higher GC contents. Thermal adaptation is one possible explanation for the positive association. Meanwhile, we propose that the elevated efficiency of DNA repair in response to heat mutagenesis might have the by-product of increasing GC content like that happens in intracellular symbionts and marine bacterioplankton.
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Testing whether an ancestral change in one trait consistently leads to the same change in the other trait would suggest the co-evolution is due to a causal link.
“To distinguish which scenario is more likely, we could test whether an ancestral change in one trait consistently leads to the same change in the other trait, which would suggest the co-evolution is due to a causal link42,43,51,85–87 (Fig. 3).”
From A phylogenetic approach to comparative genomics (2025) · cites this paper as [87]
The Results section ('Evolutionary jumps in bacterial GC contents are correlated with Topt changes'; page not provided) reports that changes in growth temperature and GC content tend to occur in the same direction. The Discussion cautions that not all increases coincide and describes the finding as a statistical correlation. The paper supports testing for coordinated trait changes, but does not say that such a result would suggest a causal link. (LLM, conf=0.84)
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Phylogenies and the Comparative Method
Felsenstein, J. (1985) · The American Naturalist · doi:10.1086/284325 · Cited by 9,793 · see citing works
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A phylogenetic approach to comparative genomics
Dewar, A. E., Belcher, L. J., & West, S. A. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-024-00803-0 · Cited by 41 · see citing works
- Authors
- Hu, E.-Z., Lan, X.-R., Liu, Z.-L., Gao, J., & Niu, D.-K.
- Affiliations
- Beijing Normal University (CN)
- Corresponding author
- Niu, Deng-Ke
- Venue
- BMC Genomics
- Published
- 2022-02-09
- Volume
- 23
- Issue
- 1
- Pages
- 110-110
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC8827189
- OpenAlex
- W4210910632
- Cited by
- 135
- References
- 1
- Citations by year
- 2026: 36 · 2025: 36 · 2024: 30 · 2023: 26 · 2022: 7
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Genomics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31671321)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- GC content, optimal growth temperature, prokaryotes, bacteria, archaea, thermal adaptation, psychrophiles, thermophiles, hyperthermophiles, DNA repair, genome composition
- MeSH terms
- Archaea, Base Composition, Phylogeny, Prokaryotic Cells, Temperature
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