Protein and DNA Sequence Determinants of Thermophilic Adaptation
Open accessAbstract
There have been considerable attempts in the past to relate phenotypic trait--habitat temperature of organisms--to their genotypes, most importantly compositions of their genomes and proteomes. However, despite accumulation of anecdotal evidence, an exact and conclusive relationship between the former and the latter has been elusive. We present an exhaustive study of the relationship between amino acid composition of proteomes, nucleotide composition of DNA, and optimal growth temperature (OGT) of prokaryotes. Based on 204 complete proteomes of archaea and bacteria spanning the temperature range from -10 degrees C to 110 degrees C, we performed an exhaustive enumeration of all possible sets of amino acids and found a set of amino acids whose total fraction in a proteome is correlated, to a remarkable extent, with the OGT. The universal set is Ile, Val, Tyr, Trp, Arg, Glu, Leu (IVYWREL), and the correlation coefficient is as high as 0.93. We also found that the G + C content in 204 complete genomes does not exhibit a significant correlation with OGT (R = -0.10). On the other hand, the fraction of A + G in coding DNA is correlated with temperature, to a considerable extent, due to codon patterns of IVYWREL amino acids. Further, we found strong and independent correlation between OGT and the frequency with which pairs of A and G nucleotides appear as nearest neighbors in genome sequences. This adaptation is achieved via codon bias. These findings present a direct link between principles of proteins structure and stability and evolutionary mechanisms of thermophylic adaptation. On the nucleotide level, the analysis provides an example of how nature utilizes codon bias for evolutionary adaptation to extreme conditions. Together these results provide a complete picture of how compositions of proteomes and genomes in prokaryotes adjust to the extreme conditions of the environment.
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The earliest amino acids used by life fit a temperate origin, not a hot one.
“Work on the addition of amino acids to the canonical repertoire suggest that the first amino acids used by life are also consistent with a temperate, rather than hot, origin of life (Brooks et al. 2002;Zeldovich et al. 2007;Fournier and Gogarten 2010).”
From Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor (2018) · cites this paper as Zeldovich et al. 2007
The abundance of amino acids I, V, Y, W, R, E, and L (IVYWREL) within protein sequences correlates strongly with an organism's optimal growth temperature.
“Abundance of the amino acids I, V, Y, W, R, E, and L (denoted as IVYWREL) within protein sequences correlates strongly with an organism's optimal growth temperature (Zeldovich et al. 2007).”
From Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor (2018) · cites this paper as Zeldovich et al. 2007
The IVYWREL content of LUCA proteins is consistent with an optimal growth temperature below 50 degrees C, indicating mesophily.
“The IVYWREL content of LUCA proteins, based on phylogenetic analysis, is consistent with an optimal growth temperature below 50 degrees C, indicating a mesophily.”
From Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor (2018) · cites this paper as Zeldovich et al. 2007
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- Authors
- Zeldovich, K. B., Berezovsky, I. N., & Shakhnovich, E. I.
- Affiliations
- Harvard University (US)
- Corresponding author
- Shakhnovich, Eugene I
- Venue
- PLoS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-01-12
- Volume
- 3
- Issue
- 1
- Pages
- e5
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC1769408
- OpenAlex
- W2026343937
- Cited by
- 325
- References
- 45
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 28 · 2023: 19 · 2022: 19 · 2021: 20 · 2020: 22 · 2019: 8 · 2018: 11 · 2017: 9 · 2016: 13 · 2015: 16 · 2014: 14 · 2013: 19 · 2012: 15
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- National University of Singapore (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- arXiv (Cornell University)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Keywords
- thermophilic adaptation, optimal growth temperature, amino acid composition, codon usage bias, nucleotide composition, GC content, prokaryotes, archaea, protein stability, extreme environments, codon usage
- MeSH terms
- Adaptation, Physiological, Amino Acid Sequence, Archaea, Bacterial Proteins, Chromosome Mapping, DNA, Molecular Sequence Data, Temperature, Conserved Sequence, Sequence Homology, Sequence Analysis, DNA, Evolution, Molecular, Sequence Analysis, Protein, Proteome
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