NORMAL GENOMIC

• Koonin EV, Wolf YI, Aravind L
• Protein fold recognition using sequence profiles and its application in structural genomics.
• Adv Protein Chem. 2000; 54: 245-75

• Frye RA
• Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins.
• Biochem Biophys Res Commun. 2000; 273: 793-8
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• Sirtuins (Sir2-like proteins) are present in prokaryotes and eukaryotes. Here, two new human sirtuins (SIRT6 and SIRT7) are found to be similar to a particular subset of insect, nematode, plant, and protozoan sirtuins. Molecular phylogenetic analysis of 60 sirtuin conserved core domain sequences from a diverse array of organisms (including archaeans, bacteria, yeasts, plants, protozoans, and metazoans) shows that eukaryotic Sir2-like proteins group into four main branches designated here as classes I-IV. Prokaryotic sirtuins include members of classes II and III. A fifth class of sirtuin is present in gram positive bacteria and Thermotoga maritima. Saccharomyces cerevisiae has five class I sirtuins. Caenorhabditis elegans and Drosophila melanogaster have sirtuin genes from classes I, II, and IV. The seven human sirtuin genes include all four classes: SIRT1, SIRT2, and SIRT3 are class I, SIRT4 is class II, SIRT5 is class III, and SIRT6 and SIRT7 are class IV.

• Cerutti L, Mian N, Bateman A
• Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain.
• Trends Biochem Sci. 2000; 25: 481-2

• Dlakic M
• Functionally unrelated signalling proteins contain a fold similar to Mg2+-dependent endonucleases.
• Trends Biochem Sci. 2000; 25: 272-3

• Sjolander K
• Phylogenetic inference in protein superfamilies: analysis of SH2 domains.
• Proc Int Conf Intell Syst Mol Biol. 1998; 6: 165-74
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• This work focuses on the inference of evolutionary relationships in protein superfamilies, and the uses of these relationships to identify key positions in the structure, to infer attributes on the basis of evolutionary distance, and to identify potential errors in sequence annotations. Relative entropy, a distance metric from information theory, is used in combination with Dirichlet mixture priors to estimate a phylogenetic tree for a set of proteins. This method infers key structural or functional positions in the molecule, and guides the tree topology to preserve these important positions within subtrees. Minimum-description-length principles are used to determine a cut of the tree into subtrees, to identify the subfamilies in the data. This method is demonstrated on SH2-domain containing proteins, resulting in a new subfamily assignment for Src2-drome and a suggested evolutionary relationship between Nck_human and Drk_drome, Sem5_caeel, Grb2_human and Grb2_chick.

• Gu X
• The age of the common ancestor of eukaryotes and prokaryotes: statistical inferences.
• Mol Biol Evol. 1997; 14: 861-6
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• In this paper, a simple distance measure was used to estimate the age (T) of the common ancestor of eukaryotes and prokaryotes which takes the rate variation among sites and the pattern of amino acid substitutions into account. Our new estimate of T based on Doolittle et al.'s data is about 2.5 billion years ago (Ga), with 95% confidence interval from 2.1 to 2.9 Ga. This result indicates (1) that Doolittle et al.'s estimate (approximately 2.0 Ga) seems too recent, and (2) that the traditional view about the divergence time between eukaryotes and prokaryotes (T0 = 3.5 Ga) can be rejected at the 0.1% significance level.