Kay Lucek1, Mabel D. Giménez2,3, Mathieu Joron4, Marina Rafajlović5,6, Jeremy B. Searle7, Nora Walden8, Anja Marie Westram9,10 and Rui Faria11,12 1Biodiversity Genomics Laboratory, Institute of Biology, University of Neuchâtel, 2000 Neuchâtel, Switzerland 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Genética Humana de Misiones (IGeHM), Parque de la Salud de la Provincia de Misiones “Dr. Ramón Madariaga,” N3300KAZ Posadas, Misiones, Argentina 3Facultad de Ciencias Exactas Químicas y Naturales, Universidad Nacional de Misiones, N3300LQH Posadas, Misiones, Argentina 4Centre d'Ecologie Fonctionnelle et Evolutive, Université de Montpellier, CNRS, EPHE, IRD, 34293 Montpellier, France 5Department of Marine Sciences, University of Gothenburg, 405 30 Gothenburg, Sweden 6Centre for Marine Evolutionary Biology, University of Gothenburg, 405 30 Gothenburg, Sweden 7Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York 14853, USA 8Centre for Organismal Studies, University of Heidelberg, 69117 Heidelberg, Germany 9Institute of Science and Technology Austria (ISTA), 3400 Klosterneuburg, Austria 10Faculty of Biosciences and Aquaculture, Nord University, 8026 Bodø, Norway 11CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado; 12BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Campus de Vairão, Universidade do Porto, 4485-661 Vairão, Portugal Correspondence: kay.lucekunine.ch; ruifariacibio.up.pt

Chromosomal rearrangements (CRs) have been known since almost the beginning of genetics. While an important role for CRs in speciation has been suggested, evidence primarily stems from theoretical and empirical studies focusing on the microevolutionary level (i.e., on taxon pairs where speciation is often incomplete). Although the role of CRs in eukaryotic speciation at a macroevolutionary level has been supported by associations between species diversity and rates of evolution of CRs across phylogenies, these findings are limited to a restricted range of CRs and taxa. Now that more broadly applicable and precise CR detection approaches have become available, we address the challenges in filling some of the conceptual and empirical gaps between micro- and macroevolutionary studies on the role of CRs in speciation. We synthesize what is known about the macroevolutionary impact of CRs and suggest new research avenues to overcome the pitfalls of previous studies to gain a more comprehensive understanding of the evolutionary significance of CRs in speciation across the tree of life.