Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (747 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The degree of similarity between sequences. Studies of amino acid sequence homology and nucleic acid sequence homology provide useful information about the genetic relatedness of genes, gene products, and species.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Homologies, Sequence; Homology, Sequence; Sequence Homologies; Homologous Sequences; Homologous Sequence; Sequence, Homologous; Sequences, Homologous; Sequence Homologs.
Where it fits in the MeSH classification
- Broader topics
- Biochemical Phenomena; Genetic Phenomena
- Narrower topics
- Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid
Related concepts
- Amino Acid Sequence Homology
- Nucleic Acid Sequence Homology
Research landscape
PubMed indexes 163,492 records tagged with the MeSH heading “Sequence Homology” (counts retrieved 2026-10-29). 2,619 of them (1.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 69,860 records.
Reviews account for 6,780 records (4.1%) and meta-analyses for 9. Randomized controlled trials number 12 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 69,860 |
| 2000-2009 | 61,954 |
| 2010-2019 | 29,059 |
| 2020 onward | 2,619 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 6,780 | 4.1% |
| Meta-analyses | 9 | 0.0% |
| Randomized controlled trials | 12 | 0.0% |
Method: PubMed query "Sequence Homology"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| HMMER web server: 2015 update | 2015 | Research article Design not recorded in structured metadata | 756 | cc by PMID 25943547 · DOI · PMC4489315 |
| GPCRdb in 2018: adding GPCR structure models and ligands | 2018 | Research article Design not recorded in structured metadata | 444 | cc by PMID 29155946 · DOI · PMC5753179 |
| Clustering predicted structures at the scale of the known protein universe | 2023 | Research article Design not recorded in structured metadata | 356 | cc by PMID 37704730 · DOI · PMC10584675 |
| The promise and pitfalls of synteny in phylogenomics | 2024 | Research article Design not recorded in structured metadata | 35 | cc by PMID 38768403 · DOI · PMC11105162 |
HMMER web server: 2015 update [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The HMMER website, available at http://www.
- Closing excerpt
- Finally, we discuss the relocation of the HMMER webserver to the European Bioinformatics Institute and the potential impact that this will have.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (198 words)
The HMMER website, available at http://www.ebi.ac.uk/Tools/hmmer/, provides access to the protein homology search algorithms found in the HMMER software suite. Since the first release of the website in 2011, the search repertoire has been expanded to include the iterative search algorithm, jackhmmer. The continued growth of the target sequence databases means that traditional tabular representations of significant sequence hits can be overwhelming to the user. Consequently, additional ways of presenting homology search results have been developed, allowing them to be summarised according to taxonomic distribution or domain architecture. The taxonomy and domain architecture representations can be used in combination to filter the results according to the needs of a user. Searches can also be restricted prior to submission using a new taxonomic filter, which not only ensures that the results are specific to the requested taxonomic group, but also improves search performance. The repertoire of profile hidden Markov model libraries, which are used for annotation of query sequences with protein families and domains, has been expanded to include the libraries from CATH-Gene3D, PIRSF, Superfamily and TIGRFAMs. Finally, we discuss the relocation of the HMMER webserver to the European Bioinformatics Institute and the potential impact that this will have.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 25943547 · DOI · PMC4489315
GPCRdb in 2018: adding GPCR structure models and ligands [2]
Abstract reading summary — source excerpts
- Opening excerpt
- G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects.
- Closing excerpt
- org.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)
G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects. Herein, we report GPCRome-wide homology models of unprecedented quality, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability. Based on the strategy of 'Less model - more Xtal', each model exploits both a main template and alternative local templates. This achieved higher similarity to new structures than any of the existing resources, and refined crystal structures with missing or distorted regions. Models are provided for inactive, intermediate and active states-except for classes C and F that so far only have inactive templates. The ligand database has separate browsers for: (i) target selection by receptor, family or class, (ii) ligand filtering based on cross-experiment activities (min, max and mean) or chemical properties, (iii) ligand source data and (iv) commercial availability. SMILES structures and activity spreadsheets can be downloaded for further processing. Furthermore, three recent landmark publications on GPCR drugs, G protein selectivity and genetic variants have been accompanied with resources that now let readers view and analyse the findings themselves in GPCRdb. Altogether, this update will enable scientific investigation for the wider GPCR community. GPCRdb is available at http://www.gpcrdb.org.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29155946 · DOI · PMC5753179
Clustering predicted structures at the scale of the known protein universe [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Proteins are key to all cellular processes and their structure is important in understanding their function and evolution.
- Closing excerpt
- On the basis of these analyses, we identify several examples of human immune-related proteins with putative remote homology in prokaryotic species, illustrating the value of this resource for studying protein function and evolution across the tree of life.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (200 words)
Proteins are key to all cellular processes and their structure is important in understanding their function and evolution. Sequence-based predictions of protein structures have increased in accuracy1, and over 214 million predicted structures are available in the AlphaFold database2. However, studying protein structures at this scale requires highly efficient methods. Here, we developed a structural-alignment-based clustering algorithm-Foldseek cluster-that can cluster hundreds of millions of structures. Using this method, we have clustered all of the structures in the AlphaFold database, identifying 2.30 million non-singleton structural clusters, of which 31% lack annotations representing probable previously undescribed structures. Clusters without annotation tend to have few representatives covering only 4% of all proteins in the AlphaFold database. Evolutionary analysis suggests that most clusters are ancient in origin but 4% seem to be species specific, representing lower-quality predictions or examples of de novo gene birth. We also show how structural comparisons can be used to predict domain families and their relationships, identifying examples of remote structural similarity. On the basis of these analyses, we identify several examples of human immune-related proteins with putative remote homology in prokaryotic species, illustrating the value of this resource for studying protein function and evolution across the tree of life.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37704730 · DOI · PMC10584675
The promise and pitfalls of synteny in phylogenomics [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Reconstructing the tree of life remains a central goal in biology.
- Closing excerpt
- Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the tree of life.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Reconstructing the tree of life remains a central goal in biology. Early methods, which relied on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the tree of life, 2 recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in 2 or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. This Essay identifies and discusses specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the tree of life.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38768403 · DOI · PMC11105162
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences [5]
- Research article A microhomology-mediated break-induced replication model for the origin of human copy number variation [6]
- Research article Mechanism and role of PDZ domains in signaling complex assembly [7]
- Research article Issues in searching molecular sequence databases [8]
- Research article Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families [9]
- Research article Alignment-free sequence comparison-a review [10]
References
- Finn RD, Clements J, Arndt W, Miller BL, Wheeler TJ, Schreiber F, et al.. HMMER web server: 2015 update. . 2015. PMID 25943547 · DOI · PMC4489315
- Pándy-Szekeres G, Munk C, Tsonkov TM, Mordalski S, Harpsøe K, Hauser AS, et al.. GPCRdb in 2018: adding GPCR structure models and ligands. . 2018. PMID 29155946 · DOI · PMC5753179
- Barrio-Hernandez I, Yeo J, Jänes J, Mirdita M, Gilchrist CLM, Wein T, et al.. Clustering predicted structures at the scale of the known protein universe. . 2023. PMID 37704730 · DOI · PMC10584675
- Steenwyk JL, King N. The promise and pitfalls of synteny in phylogenomics. . 2024. PMID 38768403 · DOI · PMC11105162
- Koonin EV, Dolja VV. Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. Crit Rev Biochem Mol Biol. 1993. PMID 8269709 · DOI
- Hastings PJ, Ira G, Lupski JR. A microhomology-mediated break-induced replication model for the origin of human copy number variation. PLoS Genet. 2009. PMID 19180184 · DOI · PMC2621351
- Harris BZ, Lim WA. Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci. 2001. PMID 11591811 · DOI
- Altschul SF, Boguski MS, Gish W, Wootton JC. Issues in searching molecular sequence databases. Nat Genet. 1994. PMID 8162065 · DOI
- Schepers GE, Teasdale RD, Koopman P. Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families. Dev Cell. 2002. PMID 12194848 · DOI
- Vinga S, Almeida J. Alignment-free sequence comparison-a review. Bioinformatics. 2003. PMID 12611807 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.