期刊
MOLECULAR BIOLOGY AND EVOLUTION
卷 34, 期 8, 页码 2016-2034出版社
OXFORD UNIV PRESS
DOI: 10.1093/molbev/msx146
关键词
cilium; ciliopathies; evolution; comparative genomics; phylogenetic profiling
资金
- Agence Nationale de la Recherche [BIPBIP: ANR-10-BINF-03-02, ReNaBi-IFB: ANR-11-INBS-0013]
- Fondation pour la Recherche Medicale [DBI20131228569]
- CNRS
- Universite de Strasbourg
- Faculte de Medecine de Strasbourg
Cilia (flagella) are important eukaryotic organelles, present in the Last Eukaryotic Common Ancestor, and are involved in cell motility and integration of extracellular signals. Ciliary dysfunction causes a class of genetic diseases, known as ciliopathies, however current knowledge of the underlying mechanisms is still limited and a better characterization of genes is needed. As cilia have been lost independently several times during evolution and they are subject to important functional variation between species, ciliary genes can be investigated through comparative genomics. We performed phylogenetic profiling by predicting orthologs of human protein-coding genes in 100 eukaryotic species. The analysis integrated three independent methods to predict a consensus set of 274 ciliary genes, including 87 new promising candidates. A fine-grained analysis of the phylogenetic profiles allowed a partitioning of ciliary genes into modules with distinct evolutionary histories and ciliary functions (assembly, movement, centriole, etc.) and thus propagation of potential annotations to previously undocumented genes. The cilia/basal body localization was experimentally confirmed for five of these previously unannotated proteins (LRRC23, LRRC34, TEX9, WDR27, and BIVM), validating the relevance of our approach. Furthermore, our multi-level analysis sheds light on the core gene sets retained in gameteonly flagellates or Ecdysozoa for instance. By combining gene-centric and species-oriented analyses, this work reveals new ciliary and ciliopathy gene candidates and provides clues about the evolution of ciliary processes in the eukaryotic domain. Additionally, the positive and negative reference gene sets and the phylogenetic profile of human genes constructed during this study can be exploited in future work.
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