The evolutionary traceability of a protein

  • Orthologs document the evolution of genes and metabolic capacities encoded in extant and ancient genomes. However, the similarity between orthologs decays with time, and ultimately it becomes insufficient to infer common ancestry. This leaves ancient gene set reconstructions incomplete and distorted to an unknown extent. Here we introduce the "evolutionary traceability" as a measure that quantifies, for each protein, the evolutionary distance beyond which the sensitivity of the ortholog search becomes limiting. Using yeast, we show that genes that were thought to date back to the last universal common ancestor are of high traceability. Their functions mostly involve catalysis, ion transport, and ribonucleoprotein complex assembly. In turn, the fraction of yeast genes whose traceability is not sufficient to infer their presence in last universal common ancestor is enriched for regulatory functions. Computing the traceabilities of genes that have been experimentally characterized as being essential for a self-replicating cell reveals that many of the genes that lack orthologs outside bacteria have low traceability. This leaves open whether their orthologs in the eukaryotic and archaeal domains have been overlooked. Looking at the example of REC8, a protein essential for chromosome cohesion, we demonstrate how a traceability-informed adjustment of the search sensitivity identifies hitherto missed orthologs in the fast-evolving microsporidia. Taken together, the evolutionary traceability helps to differentiate between true absence and nondetection of orthologs, and thus improves our understanding about the evolutionary conservation of functional protein networks. "protTrace," a software tool for computing evolutionary traceability, is freely available at; last accessed February 10, 2019.

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Author:Arpit Jain, Dominik Perisa, Fabian Fliedner, Arndt von Haeseler, Ingo EbersbergerORCiDGND
Pubmed Id:
Parent Title (English):Genome biology and evolution
Publisher:Oxford Univ. Press
Place of publication:Oxford
Contributor(s):Adam Eyre-Walker
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/01/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/09
Tag:LUCA; metabolic pathway; ortholog search; phylogenetic profile; sequence evolution; twilight zone
Page Number:15
First Page:531
Last Page:545
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Biowissenschaften / Biowissenschaften
Angeschlossene und kooperierende Institutionen / Senckenbergische Naturforschende Gesellschaft
Fachübergreifende Einrichtungen / Biodiversität und Klima Forschungszentrum (BiK-F)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0