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Evolution of Gene Regulation in Ruminants Differs Between Evolutionary Breakpoint Regions and Homologous Synteny Blocks

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Evolution of Gene Regulation in Ruminants Differs Between Evolutionary Breakpoint Regions and Homologous Synteny Blocks Downloaded from genome.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Research Evolution of gene regulation in ruminants differs between evolutionary breakpoint regions and homologous synteny blocks Marta Farré,1,18 Jaebum Kim,2,18 Anastasia A. Proskuryakova,3,4 Yang Zhang,5 Anastasia I. Kulemzina,3 Qiye Li,6 Yang Zhou,6 Yingqi Xiong,6 Jennifer L. Johnson,7 Polina L. Perelman,3,4 Warren E. Johnson,8,9 Wesley C. Warren,10 Anna V. Kukekova,7 Guojie Zhang,6,11,12 Stephen J. O’Brien,13,14 Oliver A. Ryder,15 Alexander S. Graphodatsky,3,4 Jian Ma,5 Harris A. Lewin,16 and Denis M. Larkin1,17 1Royal Veterinary College, University of London, London NW1 0TU, United Kingdom; 2Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Korea; 3Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk 630090, Russia; 4Synthetic Biology Unit, Novosibirsk State University, Novosibirsk 630090, Russia; 5Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA; 6China National GeneBank, BGI- Shenzhen, Shenzhen 518083, China; 7Department of Animal Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA; 8Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, Virginia 22630, USA; 9Walter Reed Biosystematics Unit, Museum Support Center, Smithsonian Institution, Suitland, Maryland 20746, USA; 10Bond Life Sciences Center, University of Missouri, Columbia, Missouri 63201, USA; 11State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; 12Centre for Social Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark; 13Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199004, Russia; 14Guy Harvey Oceanographic Center, Halmos College of Natural Sciences and Oceanography, Nova Southeastern University, Fort Lauderdale, Florida 33004, USA; 15Institute for Conservation Research, San Diego Zoo, Escondido, California 92027, USA; 16Department of Evolution and Ecology and the UC Davis Genome Center, University of California, Davis, California 95616, USA; 17The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia The role of chromosome rearrangements in driving evolution has been a long-standing question of evolutionary biology. Here we focused on ruminants as a model to assess how rearrangements may have contributed to the evolution of gene regulation. Using reconstructed ancestral karyotypes of Cetartiodactyls, Ruminants, Pecorans, and Bovids, we traced pat- terns of gross chromosome changes. We found that the lineage leading to the ruminant ancestor after the split from other cetartiodactyls was characterized by mostly intrachromosomal changes, whereas the lineage leading to the pecoran ancestor (including all livestock ruminants) included multiple interchromosomal changes. We observed that the liver cell putative enhancers in the ruminant evolutionary breakpoint regions are highly enriched for DNA sequences under selective con- straint acting on lineage-specific transposable elements (TEs) and a set of 25 specific transcription factor (TF) binding motifs associated with recently active TEs. Coupled with gene expression data, we found that genes near ruminant breakpoint re- gions exhibit more divergent expression profiles among species, particularly in cattle, which is consistent with the phyloge- netic origin of these breakpoint regions. This divergence was significantly greater in genes with enhancers that contain at least one of the 25 specific TF binding motifs and located near bovidae-to-cattle lineage breakpoint regions. Taken together, by combining ancestral karyotype reconstructions with analysis of cis regulatory element and gene expression evolution, our work demonstrated that lineage-specific regulatory elements colocalized with gross chromosome rearrangements may have provided valuable functional modifications that helped to shape ruminant evolution. [Supplemental material is available for this article.] The extent that chromosome rearrangements provide a substrate Whole-genome comparisons among mammals and birds point to for natural selection during animal evolution and adaptation is still regions in genomes where the order of orthologous sequences can an outstanding question in evolutionary biology (White 1968). be maintained for tens of millions of years of evolution © 2019 Farré et al. This article is distributed exclusively by Cold Spring Harbor 18These authors contributed equally to this work. Laboratory Press for the first six months after the full-issue publication date (see Corresponding author: [email protected] http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is avail- Article published online before print. Article, supplemental material, and publi- able under a Creative Commons License (Attribution-NonCommercial 4.0 Inter- cation date are at http://www.genome.org/cgi/doi/10.1101/gr.239863.118. national), as described at http://creativecommons.org/licenses/by-nc/4.0/. 29:1–14 Published by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/19; www.genome.org Genome Research 1 www.genome.org Downloaded from genome.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Farréet al. (homologous synteny blocks [HSBs]), often demarcated by evolu- low resolution using traditional cytogenetics and genetic maps tionary breakpoint regions (EBRs) where the order of orthologous (Slate et al. 2002; Murphy et al. 2005; Kulemzina et al. 2009, sequences differs among species. Several studies have shown that 2011), as well as sequenced genomes (Elsik et al. 2009). These stud- HSBs are enriched for evolutionary conserved sequences and genes ies showed that ruminant karyotypes are populated with multiple related to basic organismal development (Larkin et al. 2009; Farré inter- and intrachromosomal rearrangements enriched for line- et al. 2016), whereas EBRs are clustered in regions with a high num- age-specific transposable elements (TEs), in contrast to other mam- ber of repetitive elements and segmental duplications (Murphy malian groups, such as primates, that had a higher percentage of et al. 2005; Bailey and Eichler 2006; Ma et al. 2006; Kehrer- intrachromosomal rearrangements in their recent evolutionary Sawatzki and Cooper 2007; Larkin et al. 2009; Farré et al. 2011) history (Kim et al. 2017). and genes related to lineage-specific biology (Elsik et al. 2009; Until recently, ancestral chromosome reconstruction lacked Groenen et al. 2012; Ullastreset al. 2014; Farré et al. 2016).The exact sufficient resolution and coverage to analyze individual EBRs or reason behind the genomic content differences between HSBs and to study the evolution of chromosomes. However, with the devel- EBRs is unknown, as well as the potential functional (nonmecha- opment of the DESCHRAMBLER algorithm, these problems have nistic) role of chromosome rearrangements in genome evolution. been tackled (Kim et al. 2017). In this study, combining in silico It is well established that chromosome rearrangements can (DESCHRAMBLER) and fluorescence in situ hybridization (FISH) have both direct and indirect effects on genomes at the molecular techniques, we described four ancestral karyotypes in the lineage level. Indirect effects include the suppression of recombination leading to cattle: Cetartiodactyl, Ruminant, Pecoran, and Bovidae. within the rearranged region (Navarro and Barton 2003; Joron The aim of this study was to utilize these reconstructed ancestral et al. 2011; Farré et al. 2013) due to incomplete pairing during mei- chromosome structures to assess the functional contribution of osis, which could lead to the accumulation of genetic incompatibil- chromosomal rearrangements to the evolution of Ruminants. ities and, in some cases, speciation (Brown and O’Neill 2010). EBRs We achieved this by integrating the results from ancestral recon- can disrupt coding sequences or alter gene expression of adjacent struction with data from selective sequence constraint (conserved genes by separating them from their regulatory elements, bringing noncoding elements [CNEs]) in Cetartiodactyls, functional con- new regulatory sequences, moving the genes to different regulatory straint (putative enhancers), and gene expression among species domains, or reconfiguring chromatin interactions by rearranging with established ancestral and derived states of local genome topologically associating domains (TADs) (Cande et al. 2009; Puig structures. et al. 2015; Krefting et al. 2018; Lazar et al. 2018). Although the relationship between chromosome rearrangements and changes Results in gene expression has been demonstrated in some species (Mar- quès-Bonet et al. 2004; Giannuzzi et al. 2014; Fuller et al. 2016), Patterns of gross chromosome evolution: from the cetartiodactyl these studies analyzed the genomic and epigenomic features in a ancestor to cattle reference genome framework, and assumed that they might be rep- Using 19 mammalian genomes, we reconstructed the most likely resentative of ancestral states, without attempting any explicit an- karyotype structures of four ancestors leading to cattle: Cetartiodac- cestral reconstruction or inferring
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