Genomic Correlates of Hyperthermostability, an Update

Abstract

It has been shown (Cambillau, C., and Claverie, J. M. (2000) J. Biol. Chem. 275, 32383-32386) that a large difference between the proportions of charged versus polar (non-charged) amino acids (CvP-bias) was an adequate, if empirical, signature of the proteome of hyperthermophilic organisms (T growth >80°C). Since that study, the number of available microbial genomes has more than doubled, raising the possibility that the simple CvP-bias rule might no longer hold. Taking advantage of the new sequence data, we re-analyzed the genomes of 9 fully sequenced thermophiles, 9 hyperthermophiles, and 53 mesothermophile microorganisms to identify the genomic correlates of hyperthermostability on a wider data set. Our new results confirm that the CvP-bias previously identified on a much smaller data set still holds. Moreover, we show that it is an optimal criterion, in the sense that it corresponds to the most discriminating factor between hyperthermophilic and mesothermophilic microorganisms in a principal component analysis. In parallel, we evaluated two other recently proposed correlates of hyperthermostability, the proteome average pI and the dinucleotide statistical index (Kawashima, T., Amano, N., Koike, H., Makino, S., Higuchi, S., Kawashima-Ohya, Y., Watanabe, K., Yamazaki, M., Kanehori, K., Kawamoto, T., Nunoshiba, T., Yamamoto, Y., Aramaki, H., Makino, K., and Suzuki, M. (2000) Proc. Natl. Acad. Sci. 97, 14257-14262). We show that the CvP-bias is the sole criterion that is able to clearly discriminate hyperthermophile from mesothermophile microorganisms on a global genomic basis.Although most organisms grow at temperatures ranging between 20 and 50°C, several archaea and a few bacteria, such as Pyrococcus and Aquifex, have been found capable of withstanding temperatures close to or higher than 100°C. Identification of the molecular basis of the increased thermostability of the proteins of such hyperthermophilic organisms is expected to help our understanding of protein folding as well as the design of enzymes retaining their activity at high temperatures (Ref. 1 and references therein). In a previous comparative study, Cambillau and Claverie (2) found that a large difference between the proportions of charged (Asp, Glu, Lys, Arg) versus polar (non-charged) (Asn, Gln, Ser, Thr) amino acids (abbreviated as CvP 1 -bias) was the most prominent signature of the hyperthermophilic life style at the proteome level. This global CvP-bias was reflected in the amino acid composition of the water-accessible residues computed from an analysis of the surface of 131 mesophilic versus 58 hyperthermophilic proteins. Given the rapidly increasing number of fully sequenced microbial genomes (more than doubled since the initial study), inferences derived in the past from correlation studies on a limited set of examples are in constant danger of being proven wrong. Now the genomes of seven new thermophilic and hyperthermophile archaea and of three new thermophilic bacteria have been deciphered. Besides these thermophilic organisms, num...

Classification and regression tree (CART) analyses of genomic signatures reveal sets of tetramers that discriminate temperature optima of archaea and bacteria

“…Amino acid use by thermophiles includes the replacement of polar non-charged amino acids with charged amino acids such as lysine, arginine, aspartic acid and glutamic acid (Cambillau andClaverie 2000, Suhre andClaverie 2003). A similar analysis of two psychrophilic archaea (Saunders et al 2003) showed a bias for polar noncharged amino acids.…”

“…In a study of seven complete and several partial genomes, Karlin et al (1997) noted that the three thermophiles had significantly lower proportions of the dinucleotide CG. Kawashima et al (2000) and Suhre and Claverie (2003) concluded that the "dinucleotide statistical index," computed from dinucleotide frequencies, showed more pure pyrimidine dinucleotides (TC combinations) and more pure purine dinucleotides (AG combinations) in hyperthermophiles. An in vitro investigation by Xia et al (2002) of Pasteurella multocida cultivated for approximately 14,400 generations at 45°C (i.e., above the optimum temperature of 37°C) resulted in a decrease of GC% and an increase of TA, TT and AA dimers.…”

Accelerated removal of deamidated proteins and endogenous electric fields: possible implications

“…CH-PO value for hyperthermophilic proteins is higher (10 ÷ 15.0) in comparison with mesophilic (-5.0 ÷ 5.0) ones (Suhre and Claverie 2003). Polar residues, tending to introduce the aqueous solvent into the core of the protein, are less represented in hyperthermophilic proteins, that are stabilized by a network of ion bonds at the protein surface (Kumar and Nussinov 2001).…”

“…A lot of thermostable proteins display a large difference between charged (Asp, Glu, Lys, Arg) versus polar (Asn, Gln, Ser, Thr) amino acids (Suhre and Claverie 2003). CH-PO value for hyperthermophilic proteins is higher (10 ÷ 15.0) in comparison with mesophilic (-5.0 ÷ 5.0) ones (Suhre and Claverie 2003).…”

cDNA Cloning and Expression of the Cardiac Na+/Ca2+ Exchanger from Mozambique Tilapia (Oreochromis mossambicus) Reveal a Teleost Membrane Transporter with Mammalian Temperature Dependence

“…In addition, it is not known if membrane proteins (which may make up ϳ30% of the proteome of an organism) employ the same adaptations to temperature as do soluble proteins. The vast majority of functional data examining protein temperature adaptation are derived from soluble proteins (64, 68 -70) and, in the case of comparative proteomic studies (71)(72)(73), fail to differentially treat soluble and membrane proteins in their analysis. These caveats advocate the study of membrane protein temperature dependence on a case-by-case basis, preferably using orthologs that are highly conserved.…”