Evolutionary profiles from the QR factorization of multiple sequence alignments.
We present an algorithm to generate complete evolutionary profiles that represent the topology of the molecular phylogenetic tree of the homologous group. The method, based on the multidimensional QR factorization of numerically encoded multiple sequence alignments, removes redundancy from the alignments and orders the protein sequences by increasing linear dependence, resulting in the identification of a minimal basis set of sequences that spans the evolutionary space of the homologous group of proteins. We observe a general trend that these smaller, more evolutionarily balanced profiles have comparable and, in many cases, better performance in database searches than conventional profiles containing hundreds of sequences, constructed in an iterative and computationally intensive procedure. For more diverse families or superfamilies, with sequence identity <30%, structural alignments, based purely on the geometry of the protein structures, provide better alignments than pure sequence-based methods. Merging the structure and sequence information allows the construction of accurate profiles for distantly related groups. These structure-based profiles outperformed other sequence-based methods for finding distant homologs and were used to identify a putative class II cysteinyl-tRNA synthetase (CysRS) in several archaea that eluded previous annotation studies. Phylogenetic analysis showed the putative class II CysRSs to be a monophyletic group and homology modeling revealed a constellation of active site residues similar to that in the known class I CysRS.
Sethi
Anurag
A
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
O'Donoghue
Patrick
P
Luthey-Schulten
Zaida
Z
D000465:Algorithms; D000595:Amino Acid Sequence; D000619:Aminohydrolases / Q000235:genetics; D001105:Archaea / Q000235:genetics; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D016415:Sequence Alignment
C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases
Protein Sci. 1995 Feb;4(2):268-74
7757015
FEBS Lett. 2002 Mar 6;514(1):34-6
11904177
Proteins. 1997 Jul;28(3):405-20
9223186
Structure. 1997 Aug 15;5(8):1093-108
9309224
Science. 1997 Nov 7;278(5340):1119-22
9353192
J Mol Biol. 2005 Feb 25;346(3):875-94
15713469
Nat Struct Biol. 2002 Apr;9(4):257-62
11887185
Nucleic Acids Res. 2003 Jan 1;31(1):365-70
12520024
J Mol Biol. 2003 Apr 11;327(5):911-7
12662918
Microbiol Mol Biol Rev. 2003 Dec;67(4):550-73
14665676
J Bacteriol. 2004 Jan;186(1):8-14
14679218
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D189-92
14681391
J Mol Biol. 1995 Apr 7;247(4):536-40
7723011
Biochimie. 1999 Nov;81(11):1037-9
10575359
Nucleic Acids Res. 2000 Mar 15;28(6):1481-8
10684945
Microbiol Mol Biol Rev. 2000 Mar;64(1):202-36
10704480
Comput Chem. 2001 Jul;25(4):329-39
11459349
J Struct Biol. 2001 May-Jun;134(2-3):257-68
11551184
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14292-7
11717392
Science. 1996 Aug 23;273(5278):1058-73
8688087