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Edited by David M. Hillis, The University of Texas at Austin, Austin, TX, and approved December 1, 2017 (received for review May 8, 2017)
Significance
Comparisons of genome function between species are providing important insight into the evolutionary origins of diversity. Here, we show that comparative functional genomics studies can come to the wrong conclusions if they do not take the relationships of species into account and instead rely on pairwise comparisons between species, as is common practice. We reexamined two previously published studies and found problems with pairwise comparisons that draw both their original conclusions into question. One study found support for the ortholog conjecture, and the other concluded that evolution of gene expression differed in pattern and process between animal phyla vs. within animal phyla. Our results show that, to answer evolutionary questions about genome function, it is critical to consider evolutionary relationships.
Abstract
There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here, we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to have more similar attributes (expression in this case) than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead, we find that they reflect species relationships. These reanalyses concretely show the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data.
Footnotes
- ↵1To whom correspondence should be addressed. Email: casey.dunn{at}yale.edu.
↵2Present address: Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511.
Author contributions: C.W.D., F.Z., C.M., S.S., and A.H. designed research; C.W.D. and F.Z. performed research; C.W.D. and F.Z. analyzed data; and C.W.D., F.Z., C.M., S.S., and A.H. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1707515115/-/DCSupplemental.
- Copyright © 2018 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
- aDepartment of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912;
- bDepartment of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095;
- cDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616;
- dSars International Centre for Marine Molecular Biology, University of Bergen, Bergen 5006, Norway
Edited by David M. Hillis, The University of Texas at Austin, Austin, TX, and approved December 1, 2017 (received for review May 8, 2017)
Significance
Comparisons of genome function between species are providing important insight into the evolutionary origins of diversity. Here, we show that comparative functional genomics studies can come to the wrong conclusions if they do not take the relationships of species into account and instead rely on pairwise comparisons between species, as is common practice. We reexamined two previously published studies and found problems with pairwise comparisons that draw both their original conclusions into question. One study found support for the ortholog conjecture, and the other concluded that evolution of gene expression differed in pattern and process between animal phyla vs. within animal phyla. Our results show that, to answer evolutionary questions about genome function, it is critical to consider evolutionary relationships.
Abstract
There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here, we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to have more similar attributes (expression in this case) than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead, we find that they reflect species relationships. These reanalyses concretely show the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data.
- phylogenetics
- functional genomics
- gene expression
- ortholog conjecture
- hourglass
Footnotes
- ↵1To whom correspondence should be addressed. Email: casey.dunn{at}yale.edu.
↵2Present address: Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511.
Author contributions: C.W.D., F.Z., C.M., S.S., and A.H. designed research; C.W.D. and F.Z. performed research; C.W.D. and F.Z. analyzed data; and C.W.D., F.Z., C.M., S.S., and A.H. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1707515115/-/DCSupplemental.
- Copyright © 2018 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Pairwise comparisons among species are problematic
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