title: No Evidence for Phylostratigraphic Bias Impacting Inferences on Patterns of Gene Emergence and Evolution.
abstract: Phylostratigraphy is a computational framework for dating the emergence of DNA and protein sequences in a phylogeny. It has been extensively applied to make inferences on patterns of genome evolution, including patterns of disease gene evolution, ontogeny and de novo gene origination. Phylostratigraphy typically relies on BLAST searches along a species tree, but new simulation studies have raised concerns about the ability of BLAST to detect remote homologues and its impact on phylostratigraphic inferences. Here, we re-assessed these simulations. We found that, even with a possible overall BLAST false negative rate between 11-15%, the large majority of sequences assigned to a recent evolutionary origin by phylostratigraphy is unaffected by technical concerns about BLAST. Where the results of the simulations did cast doubt on previously reported findings, we repeated the original analyses but now excluded all questionable sequences. The originally described patterns remained essentially unchanged. These new analyses strongly support phylostratigraphic inferences, including: genes that emerged after the origin of eukaryotes are more likely to be expressed in the ectoderm than in the endoderm or mesoderm in Drosophila, and the de novo emergence of protein-coding genes from non-genic sequences occurs through proto-gene intermediates in yeast. We conclude that BLAST is an appropriate and sufficiently sensitive tool in phylostratigraphic analysis that does not appear to introduce significant biases into evolutionary pattern inferences.
authors.affiliation: Laboratory of Evolutionary Genetics, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia.|Catholic University of Croatia, Zagreb, Croatia.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Domazet-Lošo
authors.affiliation: Department of Medicine, University of California, San Diego, CA.
authors.forename: Anne-Ruxandra
authors.initials: AR
authors.lastname: Carvunis
authors.affiliation: Evolutionary Genomics Group, Research Programme on Biomedical Informatics, Hospital del Mar Research Institute, Universitat Pompeu Fabra, Barcelona, Spain.|Catalan Institution for Research and Advanced Studies, Barcelona, Spain.
authors.forename: M Mar
authors.initials: MM
authors.lastname: Albà
authors.affiliation: Laboratory of Evolutionary Genetics, Division of Molecular Biology, Ruder Boškovic Institute, Zagreb, Croatia.
authors.forename: Martin Sebastijan
authors.initials: MS
authors.lastname: Šestak
authors.affiliation: Laboratory of Evolutionary Genetics, Division of Molecular Biology, Ruder Boškovic Institute, Zagreb, Croatia.
authors.forename: Robert
authors.initials: R
authors.lastname: Bakaric
authors.affiliation: Max-Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Rafik
authors.initials: R
authors.lastname: Neme
authors.affiliation: Max-Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Diethard
authors.initials: D
authors.lastname: Tautz
mesh_terms: D000818:Animals; D015982:Bias; D005075:Biological Evolution; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004330:Drosophila; D019143:Evolution, Molecular; D016678:Genome; D008957:Models, Genetic; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013997:Time Factors
keywords: BLAST; gene age estimation; genome analysis; phylostratigraphy