RT Journal Article SR Electronic T1 Increased taxon sampling reveals thousands of hidden orthologs in flatworms JF bioRxiv FD Cold Spring Harbor Laboratory SP 050724 DO 10.1101/050724 A1 José M. Martín-Durán A1 Joseph F. Ryan A1 Bruno C. Vellutini A1 Kevin Pang A1 Andreas Hejnol YR 2016 UL http://biorxiv.org/content/early/2016/08/30/050724.abstract AB Gains and losses shape the gene complement of animal lineages and are a fundamental aspect of genomic evolution. Acquiring a comprehensive view of the evolution of gene repertoires is limited by the intrinsic limitations of common sequence similarity searches and available databases. Thus, a subset of the complement of an organism consists of hidden orthologs, those with no apparent homology with common sequenced animal lineages –mistakenly considered new genes– but actually representing rapidly evolving orthologs or undetected paralogs. Here, we describe Leapfrog, a simple automated BLAST pipeline that leverages increased taxon sampling to overcome long evolutionary distances and identify hidden orthologs in large transcriptomic databases. As a case study, we used 35 transcriptomes of 29 flatworm lineages to recover 3,427 hidden orthologs, some of them not identified by OrthoFinder, a common orthogroup inference algorithm. Unexpectedly, we do not observe a correlation between the number of hidden orthologs in a lineage and its ‘average’ evolutionary rate. Hidden orthologs do not show unusual sequence composition biases (e.g. GC content, average length, domain composition) that might account for systematic errors in sequence similarity searches. Instead, gene duplication and divergence of one paralog and weak positive selection appear to underlie hidden orthology in Platyhelminthes. By using Leapfrog, we identify key centrosome-related genes and homeodomain classes previously reported as absent in free-living flatworms, e.g. planarians. Altogether, our findings demonstrate that hidden orthologs comprise a significant proportion of the gene repertoire in flatworms, qualifying the impact of gene losses and gains in gene complement evolution.