Recombinational DSBs‐intersected genes converge on specific disease‐ and adaptability‐related pathways

Motivation: The budding yeast Saccharomyces cerevisiae is a model species powerful for studying the recombination of eukaryotes. Although many recombination studies have been performed for this species by experimental methods, the population genomic study based on bioinformatics analyses is urgently needed to greatly increase the range and accuracy of recombination detection. Here, we carry out the population genomic analysis of recombination in S.cerevisiae to reveal the potential rules between recombination and evolution in eukaryotes. Results: By population genomic analysis, we discover significantly more and longer recombination events in clinical strains, which indicates that adverse environmental conditions create an obviously wider range of genetic combination in response to the selective pressure. Based on the analysis of recombinational double strand breaks (DSBs)‐intersected genes (RDIGs), we find that RDIGs significantly converge on specific disease‐ and adaptability‐related pathways, indicating that recombination plays a biologically key role in the repair of DSBs related to diseases and environmental adaptability, especially the human neurological disorders. By evolutionary analysis of RDIGs, we find that the RDIGs highly prevailing in populations of yeast tend to be more evolutionarily conserved, indicating the accurate repair of DSBs in these RDIGs is critical to ensure the eukaryotic survival or fitness. Supplementary information: Supplementary data are available at Bioinformatics online.

[1]  D. Burke,et al.  Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning. , 1995, AIDS research and human retroviruses.

[2]  D. Posada.  Evaluation of methods for detecting recombination from DNA sequences: empirical data. , 2002, Molecular biology and evolution.

[3]  Linda Z. Shi,et al.  Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells , 2013, Proceedings of the National Academy of Sciences.

[4]  Robert J Kavlock,et al.  Real-time growth kinetics measuring hormone mimicry for ToxCast chemicals in T-47D human ductal carcinoma cells. , 2013, Chemical research in toxicology.

[5]  D. Bryant,et al.  A Simple and Robust Statistical Test for Detecting the Presence of Recombination , 2006, Genetics.

[6]  Steven J. M. Jones,et al.  Circos: an information aesthetic for comparative genomics. , 2009, Genome research.

[7]  Feng Gao,et al.  The systematic analysis of ultraconserved genomic regions in the budding yeast , 2017, Bioinform..

[8]  S. Keeney,et al.  Nonparadoxical evolutionary stability of the recombination initiation landscape in yeast , 2015, Science.

[9]  D. Newman,et al.  The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance , 2015, mBio.

[10]  S. Morrical,et al.  Coordination of DNA replication and recombination activities in the maintenance of genome stability , 2011, Journal of cellular biochemistry.

[11]  J. Bartek,et al.  The DNA-damage response in human biology and disease , 2009, Nature.

[12]  D. Carroll,et al.  Genome engineering with TALENs and ZFNs: repair pathways and donor design. , 2014, Methods.

[13]  A. Vandamme,et al.  In vivo characteristics of human immunodeficiency virus type 1 intersubtype recombination: determination of hot spots and correlation with sequence similarity. , 2003, The Journal of general virology.

[14]  V. Bohr,et al.  The Impact of Base Excision DNA Repair in Age-Related Neurodegenerative Diseases , 2015, Mutation research.

[15]  T. Dexheimer.  DNA Repair Pathways and Mechanisms , 2013 .

[16]  A. Long,et al.  Standing genetic variation drives repeatable experimental evolution in outcrossing populations of Saccharomyces cerevisiae. , 2014, Molecular biology and evolution.

[17]  H. von Koskull,et al.  Distribution of chromosome breaks in measles, Fanconi's anemia and controls. , 2009, Hereditas.

[18]  M. Bennett,et al.  Role of DNA damage in atherosclerosis--bystander or participant? , 2011, Biochemical pharmacology.

[19]  D. Huson,et al.  Application of phylogenetic networks in evolutionary studies. , 2006, Molecular biology and evolution.

[20]  S. Sawyer,et al.  Possible emergence of new geminiviruses by frequent recombination. , 1999, Virology.

[21]  Neeraj K. Joshi,et al.  Gradual implementation of the meiotic recombination program via checkpoint pathways controlled by global DSB levels. , 2015, Molecular cell.

[22]  P. Jeggo,et al.  DNA repair, genome stability and cancer: a historical perspective , 2015, Nature Reviews Cancer.

[23]  Ari Löytynoja,et al.  An algorithm for progressive multiple alignment of sequences with insertions. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Lesley A. Mathews,et al.  DNA Repair of Cancer Stem Cells , 2013, Springer Netherlands.

[25]  Austin G. Meyer,et al.  Systematic humanization of yeast genes reveals conserved functions and genetic modularity , 2015, Science.

[26]  Edith D. Wong,et al.  Saccharomyces genome database informs human biology , 2017, Nucleic Acids Res..

[27]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[28]  P. Brown,et al.  Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[29]  V. Bohr,et al.  DNA Damage, DNA Repair, Aging, and Neurodegeneration. , 2015, Cold Spring Harbor perspectives in medicine.

[30]  Daniel A. Skelly,et al.  The 100-genomes strains, an S. cerevisiae resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen , 2015, Genome research.

[31]  Kara A. Bernstein,et al.  The Shu complex is a conserved regulator of homologous recombination. , 2016, FEMS yeast research.

[32]  David Posada,et al.  An Exact Nonparametric Method for Inferring Mosaic Structure in Sequence Triplets , 2007, Genetics.

[33]  M. Bennett,et al.  DNA damage and repair in atherosclerosis. , 2006, Cardiovascular research.

[34]  Shyamasree Laskar,et al.  Both the Charged Linker Region and ATPase Domain of Hsp90 Are Essential for Rad51-Dependent DNA Repair , 2014, Eukaryotic Cell.

[35]  Steven Salzberg,et al.  Mugsy: fast multiple alignment of closely related whole genomes , 2010, Bioinform..

[36]  G. Copenhaver,et al.  Meiotic recombination gets stressed out: CO frequency is plastic under pressure. , 2017, Current opinion in plant biology.

[37]  C. Stoeckert,et al.  OrthoMCL: identification of ortholog groups for eukaryotic genomes. , 2003, Genome research.

[38]  Ziheng Yang.  PAML 4: phylogenetic analysis by maximum likelihood. , 2007, Molecular biology and evolution.

[39]  Michael D. Gonzales,et al.  Gene Evolutionary Trajectories and GC Patterns Driven by Recombination in Zea mays , 2016, Front. Plant Sci..

[40]  V. Micheli,et al.  Saccharomyces Cerevisiae as a Tool to Evaluate the Effects of Herbicides on Eukaryotic Life , 2011 .

[41]  Mark J. Gibbs,et al.  Sister-Scanning: a Monte Carlo procedure for assessing signals in recombinant sequences , 2000, Bioinform..

[42]  Jianping Xu,et al.  Genetic diversity and recombination in natural populations of the nematode-trapping fungus Arthrobotrys oligospora from China , 2013, Ecology and evolution.

[43]  E. Cho,et al.  Expression of the Hutchinson-Gilford Progeria Mutation Leads to Aberrant Dentin Formation , 2018, Scientific Reports.

[44]  Haoyue Zhang,et al.  Mechanisms controlling the smooth muscle cell death in progeria via down-regulation of poly(ADP-ribose) polymerase 1 , 2014, Proceedings of the National Academy of Sciences.

[45]  Darren Martin,et al.  RDP: detection of recombination amongst aligned sequences , 2000, Bioinform..

[46]  Ziheng Yang,et al.  The effect of insertions, deletions, and alignment errors on the branch-site test of positive selection. , 2010, Molecular biology and evolution.

[47]  A. Seluanov,et al.  Changes in DNA repair during aging , 2007, Nucleic acids research.

[48]  D. Amberg,et al.  Classical Genetics with Saccharomyces cerevisiae. , 2016, Cold Spring Harbor protocols.

[49]  C. Ohlsson,et al.  Expression of the Hutchinson-Gilford Progeria Mutation during Osteoblast Development Results in Loss of Osteocytes, Irregular Mineralization, and Poor Biomechanical Properties* , 2012, The Journal of Biological Chemistry.

[50]  B. Murrell,et al.  RDP4: Detection and analysis of recombination patterns in virus genomes , 2015, Virus evolution.

[51]  T. Speed,et al.  GOstat: find statistically overrepresented Gene Ontologies within a group of genes. , 2004, Bioinformatics.

[52]  John Maynard Smith,et al.  Analyzing the mosaic structure of genes , 1992, Journal of Molecular Evolution.

[53]  Dieter Lang,et al.  Predicting drug metabolism: experiment and/or computation? , 2015, Nature Reviews Drug Discovery.

[54]  K. Katoh,et al.  MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability , 2013, Molecular biology and evolution.

[55]  A. Nicolas,et al.  Initiation of meiotic homologous recombination: flexibility, impact of histone modifications, and chromatin remodeling. , 2015, Cold Spring Harbor perspectives in biology.