“Homology” in proteins and nucleic acids: A terminology muddle and a way out of it

Reeck, Gerald R.; Haën, Christoph de; Teller, David C.; Doolittle, Russell F.; Fitch, Walter M.; Dickerson, Richard E.; Chambon, Pierre; McLachlan, Anton; Margoliash, E.; Jukes, Thomas H.; Zuckerkandl, Emile

doi:10.1016/0092-8674(87)90322-9

Cited by 205 publications

(85 citation statements)

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“…Many genes currently are classified on the basis of pairwise similarity. Although similarity-based techniques are essential tools for searching enormous databases and making first approximations of gene homology, phylogeny-based methods offer a more precise and accurate way to classify and name genes (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…However, currently there exist no precise descriptions of the evolutionary relationships of type II͞IV NTPase gene superfamily members. Although pairwise sequence similarities and alignments provide important clues to understanding the relationship between genes, they do not give a clear representation of gene grouping, history, or homology (24,25). Because they have evolved largely by a process of lineage splitting and divergence, genes can be organized into nested hierarchies.…”

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confidence: 99%

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Phylogeny of genes for secretion NTPases: Identification of the widespread tadA subfamily and development of a diagnostic key for gene classification

Planet

Kachlany

DeSalle

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

188

166

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Macromolecular transport systems in bacteria currently are classified by function and sequence comparisons into five basic types. In this classification system, type II and type IV secretion systems both possess members of a superfamily of genes for putative NTP hydrolase (NTPase) proteins that are strikingly similar in structure, function, and sequence. These include VirB11, TrbB, TraG, GspE, PilB, PilT, and ComG1. The predicted protein product of tadA, a recently discovered gene required for tenacious adherence of Actinobacillus actinomycetemcomitans, also has significant sequence similarity to members of this superfamily and to several unclassified and uncharacterized gene products of both Archaea and Bacteria. To understand the relationship of tadA and tadA-like genes to those encoding the putative NTPases of type II͞IV secretion, we used a phylogenetic approach to obtain a genealogy of 148 NTPase genes and reconstruct a scenario of gene superfamily evolution. In this phylogeny, clear distinctions can be made between type II and type IV families and their constituent subfamilies. In addition, the subgroup containing tadA constitutes a novel and extremely widespread subfamily of the family encompassing all putative NTPases of type IV secretion systems. We report diagnostic amino acid residue positions for each major monophyletic family and subfamily in the phylogenetic tree, and we propose an easy method for precisely classifying and naming putative NTPase genes based on phylogeny. This molecular key-based method can be applied to other gene superfamilies and represents a valuable tool for genome analysis.conjugation ͉ ATPase ͉ Archaea ͉ molecular key ͉ Walker box

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Phylogeny of genes for secretion NTPases: Identification of the widespread tadA subfamily and development of a diagnostic key for gene classification

Planet

Kachlany

DeSalle

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

188

166

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“…The similarities are obvious when the sequences are aligned and since they extend over most of the length of each protein it is reasonable to conclude that the similarity arises from common ancestry: these enzymes constitute a homologous family [17].…”

Section: Discussionmentioning

confidence: 99%

Pyruvate decarboxylase is like acetolactate synthase (ILV2) and not like the pyruvate dehydrogenase E1 subunit

Green

1989

FEBS Letters

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Protein sequences of pyruvate decarboxylase (PDC) derived from cloned yeast (Saccharomyces cerevisiae) and bacterial (Zymomonas mobilis) genes were compared with each other and with sequence databases. Extensive sequence similarities were found between them and with two others: cytochrome-linked pyruvate oxidase from Escherichia coli and acetolactate synthase (ilvl in E. coli; IL V2 gene in S. cerevisiae). All catalyse decarboxylation of pyruvate using thiamine pyrophosphate (TPP) as cofactor. General overall similarity suggests common ancestry for these enzymes. None of the sequences was similar to the El component of pyruvate dehydrogenase from E. coli which also decarboxylates pyruvate with the help of TPP.

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“…It is, or should be, the primary concept of relationship when using sequences for phylogenetic purposes. In molecular biology, it is unfortunate that the word homology has long been used as a synonym for similarity (Margoliash 1969;Reeck et al 1987). As discussed below, similarity is one of several criteria that can be used to help infer homology, but making the words synonymous confuses empirical measurements (similarity) with inferred conclusions (homology).…”

Section: Terminologymentioning

confidence: 99%

Molecular homology and multiple-sequence alignment: an analysis of concepts and practice

Morrison

Morgan

Kelchner

2015

Aust. Systematic Bot.

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Abstract. Sequence alignment is just as much a part of phylogenetics as is tree building, although it is often viewed solely as a necessary tool to construct trees. However, alignment for the purpose of phylogenetic inference is primarily about homology, as it is the procedure that expresses homology relationships among the characters, rather than the historical relationships of the taxa. Molecular homology is rather vaguely defined and understood, despite its importance in the molecular age. Indeed, homology has rarely been evaluated with respect to nucleotide sequence alignments, in spite of the fact that nucleotides are the only data that directly represent genotype. All other molecular data represent phenotype, just as do morphology and anatomy. Thus, efforts to improve sequence alignment for phylogenetic purposes should involve a more refined use of the homology concept at a molecular level. To this end, we present examples of molecular-data levels at which homology might be considered, and arrange them in a hierarchy. The concept that we propose has many levels, which link directly to the developmental and morphological components of homology. Of note, there is no simple relationship between gene homology and nucleotide homology. We also propose terminology with which to better describe and discuss molecular homology at these levels. Our over-arching conceptual framework is then used to shed light on the multitude of automated procedures that have been created for multiple-sequence alignment. Sequence alignment needs to be based on aligning homologous nucleotides, without necessary reference to homology at any other level of the hierarchy. In particular, inference of nucleotide homology involves deriving a plausible scenario for molecular change among the set of sequences. Our clarifications should allow the development of a procedure that specifically addresses homology, which is required when performing alignment for phylogenetic purposes, but which does not yet exist.

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“Homology” in proteins and nucleic acids: A terminology muddle and a way out of it

Cited by 205 publications

References 0 publications

Phylogeny of genes for secretion NTPases: Identification of the widespread tadA subfamily and development of a diagnostic key for gene classification

Phylogeny of genes for secretion NTPases: Identification of the widespread tadA subfamily and development of a diagnostic key for gene classification

Pyruvate decarboxylase is like acetolactate synthase (ILV2) and not like the pyruvate dehydrogenase E1 subunit

Molecular homology and multiple-sequence alignment: an analysis of concepts and practice

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