Pairwise comparisons across species are problematic when analyzing functional genomic data

Dunn, Casey W.; Zapata, Felipe; Munro, Catriona; Siebert, Stefan; Hejnol, Andreas

doi:10.1073/pnas.1707515115

Cited by 91 publications

(152 citation statements)

References 66 publications

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“…a, Table S10). Comparing gene expression across species requires prior knowledge of phylogenetic relationships (Dunn et al ., ) to account for neutral fluctuations in gene expression levels in different lineages (Rohlfs et al ., ). Such analyses could not previously be performed with sufficient confidence because (1) branch lengths, as required for downstream analyses, could not be estimated accurately, and (2) the relationship among taxa with newly generated transcriptomes, in particular the placement of the emerging model species Arabis alpina , has not been resolved consistently before our phylogenomic study (Willing et al ., ).…”

Section: Resultsmentioning

confidence: 99%

Resolving the backbone of the Brassicaceae phylogeny for investigating trait diversity

et al. 2019

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Summary The Brassicaceae family comprises c. 4000 species including economically important crops and the model plant Arabidopsis thaliana. Despite their importance, the relationships among major lineages in the family remain unresolved, hampering comparative research. Here, we inferred a Brassicaceae phylogeny using newly generated targeted enrichment sequence data of 1827 exons (> 940 000 bases) representing 63 species, as well as sequenced genome data of 16 species, together representing 50 of the 52 currently recognized Brassicaceae tribes. A third of the samples were derived from herbarium material, facilitating broad taxonomic coverage of the family. Six major clades formed successive sister groups to the rest of Brassicaceae. We also recovered strong support for novel relationships among tribes, and resolved the position of 16 taxa previously not assigned to a tribe. The broad utility of these phylogenetic results is illustrated through a comparative investigation of genome‐wide expression signatures that distinguish simple from complex leaves in Brassicaceae. Our study provides an easily extendable dataset for further advances in Brassicaceae systematics and a timely higher‐level phylogenetic framework for a wide range of comparative studies of multiple traits in an intensively investigated group of plants.

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Section: Resultsmentioning

confidence: 99%

Resolving the backbone of the Brassicaceae phylogeny for investigating trait diversity

et al. 2019

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“…To address these 49 questions, the ortholog conjecture was put forth, a major thesis stating that orthologs are more 50 likely to retain function between species than paralogs, which will tend to diverge in function after 51 duplication due to drift and relaxed selection [10,11]. This conjecture underlies common methods 52 by which functions are assigned to newly discovered or understudied genes in un-annotated 53 4 genomes [12], but tests of the conjecture have not been without criticism, at least in part due to the 54 reliance on indirect functional assays [13][14][15]. 55In particular, direct experimental testing of the ortholog conjecture and retention of ancestral gene 56 function is difficult, as neither detailed cellular and molecular function information nor consistent 57 experimental assays are widely available for many genes across species, and much of the 58 functional information assigned to new genes in understudied species is assigned by sequence 59 similarity to genes of known function, further compounding the problem.…”

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confidence: 99%

Humanization of yeast genes with multiple human orthologs reveals principles of functional divergence between paralogs

Laurent

Garge

et al. 2019

Preprint

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1Despite over a billion years of evolutionary divergence, several thousand human genes possess 2 clearly identifiable orthologs in yeast, and many have undergone lineage-specific duplications in 3 one or both lineages. The ortholog conjecture postulates that orthologous genes between species 4 retain ancestral functions despite divergence over vast timescales, but duplicated genes will be free 5 to diverge in function. However, the retention of ancestral functions among co-orthologs between 6 species and within gene families has been difficult to test experimentally at scale. In order to 7 investigate how ancestral functions are retained or lost post-duplication, we systematically 8 replaced hundreds of essential yeast genes with their human orthologs from gene families that have 9 undergone lineage-specific duplications, including those with single duplications (one yeast gene 10 to two human genes, 1:2) or higher-order expansions (1:>2) in the human lineage. We observe a 11 variable pattern of replaceability across different ortholog classes, with an obvious trend towards 12 differential replaceability inside gene families, rarely observing replaceability by all members of 13 a family. We quantify the ability of various properties of the orthologs to predict replaceability, 14showing that in the case of 1:2 orthologs, replaceability is predicted largely by the divergence and 15 tissue-specific expression of the human co-orthologs, i.e. the human proteins that are less diverged 16 from their yeast counterpart and more ubiquitously expressed across human tissues more often 17 replace their single yeast ortholog. These trends were consistent with in silico simulations 18demonstrating that when only one ortholog is replaceable, it tends to be the least diverged of the 19 pair. Replaceability of yeast genes having more than two human co-orthologs was marked by 20 retention of orthologous interactions in functional or protein networks as well as by more ancestral 21 subcellular localization. Overall, we performed >400 human gene replaceability assays revealing 22 56 new human-yeast complementation pairs, thus opening up avenues to further functionally 23 characterize these human genes in a simplified organismal context. 24 25 and are distinguished from those related by speciation, termed orthologs [8,9]. Importantly, an 46 expanded family of paralogs in one lineage may be co-orthologs to a single gene in another lineage. 47How ancestral functions are partitioned, lost, or retained between paralogs and orthologs during 48 these duplication events is a major topic of study for evolutionary biology. To address these 49 questions, the ortholog conjecture was put forth, a major thesis stating that orthologs are more 50 likely to retain function between species than paralogs, which will tend to diverge in function after 51 duplication due to drift and relaxed selection [10,11]. This conjecture underlies common methods 52 by which functions are assigned to newly discovered or understudied genes in un-annotated 53 4 genomes ...

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“…Phylogeny is essential to understand biodiversity because not only does the species tree record the evolutionary history, the divergence events and their pace, but it is also the framework for comparative genomics. Explicitly tree-based analyses of associations between phenotypic and genomic traits are necessary to evaluate the statistical (in)dependence of data points [32]. We can only understand the origin and later modifications of phenotypes when they can be mapped onto correctly reconstructed phylogenetic trees.…”

Section: Centrality Of the Phylogeny For Comparative Studiesmentioning

confidence: 99%

Comparative Phylogenomics, a Stepping Stone for Bird Biodiversity Studies

Stiller

2019

Diversity

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Birds are a group with immense availability of genomic resources, and hundreds of forthcoming genomes at the doorstep. We review recent developments in whole genome sequencing, phylogenomics, and comparative genomics of birds. Short read based genome assemblies are common, largely due to efforts of the Bird 10K genome project (B10K). Chromosome-level assemblies are expected to increase due to improved long-read sequencing. The available genomic data has enabled the reconstruction of the bird tree of life with increasing confidence and resolution, but challenges remain in the early splits of Neoaves due to their explosive diversification after the Cretaceous-Paleogene (K-Pg) event. Continued genomic sampling of the bird tree of life will not just better reflect their evolutionary history but also shine new light onto the organization of phylogenetic signal and conflict across the genome. The comparatively simple architecture of avian genomes makes them a powerful system to study the molecular foundation of bird specific traits. Birds are on the verge of becoming an extremely resourceful system to study biodiversity from the nucleotide up.

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Pairwise comparisons across species are problematic when analyzing functional genomic data

Cited by 91 publications

References 66 publications

Resolving the backbone of the Brassicaceae phylogeny for investigating trait diversity

Resolving the backbone of the Brassicaceae phylogeny for investigating trait diversity

Humanization of yeast genes with multiple human orthologs reveals principles of functional divergence between paralogs

Comparative Phylogenomics, a Stepping Stone for Bird Biodiversity Studies

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