Identification of mammalian orthologs using local synteny
Open accessAbstract
Background: Accurate determination of orthology is central to comparative genomics. For vertebrates in particular, very large gene families, high rates of gene duplication and loss, multiple mechanisms of gene duplication, and high rates of retrotransposition all combine to make inference of orthology between genes difficult. Many methods have been developed to identify orthologous genes, mostly based upon analysis of the inferred protein sequence of the genes. More recently, methods have been proposed that use genomic context in addition to protein sequence to improve orthology assignment in vertebrates. Such methods have been most successfully implemented in fungal genomes and have long been used in prokaryotic genomes, where gene order is far less variable than in vertebrates. However, to our knowledge, no explicit comparison of synteny and sequence based definitions of orthology has been reported in vertebrates, or, more specifically, in mammals. Results: We test a simple method for the measurement and utilization of gene order (local synteny) in the identification of mammalian orthologs by investigating the agreement between coding sequence based orthology (Inparanoid) and local synteny based orthology. In the 5 mammalian genomes studied, 93% of the sampled inter-species pairs were found to be concordant between the two orthology methods, illustrating that local synteny is a robust substitute to coding sequence for identifying orthologs. However, 7% of pairs were found to be discordant between local synteny and Inparanoid. These cases of discordance result from evolutionary events including retrotransposition and genome rearrangements. Conclusions: By analyzing cases of discordance between local synteny and Inparanoid we show that local synteny can distinguish between true orthologs and recent retrogenes, can resolve ambiguous many-to-many orthology relationships into one-to-one ortholog pairs, and might be used to identify cases of non-orthologous gene displacement by retroduplicated paralogs.
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Orthologous chains tend to cover several genes located in a conserved order, resulting in higher synteny values, which can help distinguish orthologs from paralogs.
“Orthologous chains tend to cover several genes located in a conserved order, resulting in higher synteny values, which can help to distinguish orthologs from paralogs (14, 41–43).”
From Integrating gene annotation with orthology inference at scale (2023) · cites this paper as [42]
The Results (‘Using Local Synteny to Infer Orthology,’ page unavailable) define synteny by matches among neighboring genes, and the Conclusions say local synteny can distinguish true orthologs from recent retrogenes. But the Methods (‘Local Synteny,’ page unavailable) explicitly say those matches need not be co-linear, so the paper does not support conserved gene order as a requirement or describe the claimed orthologous chains. (LLM, conf=0.87)
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Integrating gene annotation with orthology inference at scale
Kirilenko, B. M., Munegowda, C., Osipova, E., Jebb, D., Sharma, V., Blumer, M., Morales, A. E., Ahmed, A.-W., Kontopoulos, D.-G., Hilgers, L., et al. (2023) · Science · doi:10.1126/science.abn3107 · Cited by 209 · see citing works
- Authors
- Jun, J., Mandoiu, I. I., & Nelson, C. E.
- Affiliations
- University of Connecticut (US)
- Corresponding author
- Nelson, Craig E
- Venue
- BMC Genomics
- Published
- 2009-12
- Volume
- 10
- Issue
- 1
- Pages
- 630-630
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC2807883
- OpenAlex
- W2125029076
- Cited by
- 78
- References
- 2
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- orthology inference, gene order, mammalian orthologs, retrotransposition, retrogenes, genome rearrangement, gene duplication, InParanoid, paralogs
- MeSH terms
- Animals, Mammals, Sequence Analysis, DNA, Gene Order, Synteny, Comparative Genomic Hybridization
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