The Role of Homology and Orthology in the Phylogenomic Analysis of Metazoan Gene Content
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Abstract
Resolving the relationships of animals (Metazoa) is crucial to our understanding of the origin of key traits such as muscles, guts, and nerves. However, a broadly accepted metazoan consensus phylogeny has yet to emerge. In part, this is because the genomes of deeply diverging and fast-evolving lineages may undergo significant gene turnover, reducing the number of orthologs shared with related phyla. This can limit the usefulness of traditional phylogenetic methods that rely on alignments of orthologous sequences. Phylogenetic analysis of gene content has the potential to circumvent this orthology requirement, with binary presence/absence of homologous gene families representing a source of phylogenetically informative characters. Applying binary substitution models to the gene content of 26 complete animal genomes, we demonstrate that patterns of gene conservation differ markedly depending on whether gene families are defined by orthology or homology, that is, whether paralogs are excluded or included. We conclude that the placement of some deeply diverging lineages may exceed the limit of resolution afforded by the current methods based on comparisons of orthologous protein sequences, and novel approaches are required to fully capture the evolutionary signal from genes within genomes.
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Several studies have already shown that gene family and unpartitioned phylogenomic analyses using more sophisticated substitution models reject Ctenophora sister in favour of Porifera sister.
“Several studies have already shown that gene family8,71 and unpartitioned phylogenomic analyses using more sophisticated substitution models8–10 reject Ctenophora sister in favour of Porifera sister.”
From Evidence for sponges as sister to all other animals from partitioned phylogenomics with mixture models and recoding (2021) · cites this paper as [71]
The Introduction and ‘Ortholog content vs homolog content in phylogenetic reconstruction’ (page unavailable) report gene-content analyses supporting sponges, rather than ctenophores, as sister to all other animals. The Phylogenetic analysis section describes binary substitution models applied to gene-content matrices, but our copy does not report an unpartitioned sequence-based phylogenomic analysis using more sophisticated substitution models. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCtenophoran gene families frequently include paralogs of the missing genes otherwise found in eumetazoans.
“they frequently include paralogs of the missing genes otherwise found in eumetazoans”
From Cambrian Sessile, Suspension Feeding Stem-Group Ctenophores and Evolution of the Comb Jelly Body Plan (2019) · cites this paper as [28]
In “Ortholog content vs homolog content in phylogenetic reconstruction” (page not provided), the paper suggests that related paralogs may have been retained in ctenophore gene families despite the apparent absence of many eumetazoan orthologs. It also offers an alternative: those sequences may be highly diverged orthologs. The claim presents the paralog interpretation as established and frequent, rather than as a possibility. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAmong the phylogenetic hypotheses proposed for deep-branching animals, Coelenterata maximizes support from independent lines of evidence.
“Among the phylogenetic hypotheses proposed for deep-branching animals, Coelenterata maximizes support from independent lines of evidence”
From Cambrian Sessile, Suspension Feeding Stem-Group Ctenophores and Evolution of the Comb Jelly Body Plan (2019) · cites this paper as [28]
In “Ortholog content vs homolog content in phylogenetic reconstruction” (page unavailable), the paper reports strong support for Coelenterata from homolog-content analysis. But its ortholog-content analysis supports a different placement of ctenophores, and the paper does not conclude that Coelenterata has the most support across independent lines of evidence. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe missing ctenophore-specific, eumetazoan orthologs represent losses rather than primary absences.
“This suggests that the missing ctenophore-specific, eumetazoan orthologs represent losses [28”
From Cambrian Sessile, Suspension Feeding Stem-Group Ctenophores and Evolution of the Comb Jelly Body Plan (2019) · cites this paper as [28]
In “Ortholog content vs homolog content in phylogenetic reconstruction,” the paper suggests that many eumetazoan orthologs may have been lost in ctenophores. It also offers an alternative: the apparently missing orthologs may still be present but too divergent for OrthoMCL to identify. The passage therefore supports loss as a possibility, not a determination that the missing orthologs represent losses rather than primary absences. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCtenophora as sister to Cnidaria (Coelenterata) has recently been recovered in morphological and gene family presence/absence analyses, as well as in preliminary efforts to eliminate heteropecilly in phylogenomics.
“We see two plausible placements, the first of which is the traditional scenario as sister to Cnidaria (Coelenterata)14 (Fig. 5a), which has recently been recovered in morphological63 and gene family presence/absence71 analyses, as well as in preliminary efforts to eliminate heteropecilly in phylogenomics10.”
From Evidence for sponges as sister to all other animals from partitioned phylogenomics with mixture models and recoding (2021) · cites this paper as [71]
Ctenophoran gene families lack many eumetazoan-specific orthologs.
“while ctenophoran gene families lack many eumetazoan-specific orthologs (as shown previously [14, 15”
From Cambrian Sessile, Suspension Feeding Stem-Group Ctenophores and Evolution of the Comb Jelly Body Plan (2019) · cites this paper as [28]
When presence or absence of protein families rather than of their constituent orthogroups was used to infer a phylogeny of the Opisthokonta, Coelenterata was strongly supported.
“When presence or absence of protein families rather than of their constituent orthogroups was used to infer a phylogeny of the Opisthokonta, Coelenterata was strongly supported [28”
From Cambrian Sessile, Suspension Feeding Stem-Group Ctenophores and Evolution of the Comb Jelly Body Plan (2019) · cites this paper as [28]
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- Authors
- Pett, W., Adamski, M., Adamska, M., Francis, W. R., Eitel, M., Pisani, D., & Wörheide, G.
- Affiliations
- Iowa State University (US)
- Australian National University (AU)
- Ludwig-Maximilians-Universität München (DE)
- University of Bristol (GB)
- Bayerische Staatssammlung für Paläontologie und Geologie (DE)
- Corresponding author
- Pett, Walker
- Wörheide, Gert
- ORCID
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-01-28
- Volume
- 36
- Issue
- 4
- Pages
- 643-649
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2951811509
- Cited by
- 57
- References
- 51
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 11 · 2018: 1
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Molecular Biology and Evolution (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, other-oa)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- French National Research Agency (ANR-10-BINF-01-01)
- National Science Foundation (DEB-1556615, DEB-1256993)
- NERC BETR (NE/P013643/1)
- LMU Munich’s Institutional Strategy LMUexcellent
- German Research Foundation (Wo896/19-1)
- European Union’s Horizon
- Marie Skłodowska-Curie (764840)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protist diversity and phylogeny
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Marine Invertebrate Physiology and Ecology
- Keywords
- metazoan phylogeny, homology, orthology, gene family evolution, gene turnover, paralogs, deep divergence
- MeSH terms
- Animals, Multigene Family, Genetic Techniques, Humans, Invertebrates, Phylogeny, Genome, Chordata
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