Genome Integrity and Instability

The research activity of the research group has as a main objective to study of the mechanism(s) that are responsible for the origin and maintenance of mammalian genome integrity. We reach our main goal through a multidisciplinary approach, combining computational analysis and whole-genome comparisons with cutting-edge experimental technologies in both somatic and meiotic cells.

More specifically, the group is currently working in the following research lines:

1. Investigate the conservation and functionality of the high-structural organization of mammalian genomes, both in the somatic and the germ line.

2. Analysis of the signalling pathway that controls the progression of meiotic recombination in mammalian meiocytes.

3. Identification of the role of the DNA damage response machinery in the DSB repair occurring during the meiotic prophase.

4. Study how the DNA damage response mechanism controls the oocyte pool in mammals.

 5. Identification of non-annotated genes in the mammalian genome required to complete meiosis.

 6. Identification of the genetic basis of reproductive isolation and barriers of gene flow in mammalian natural populations.

7. Development of a cell line repository of endangered mammalian species.

 8. Implementation of integrative bioinformatics and informatic tools for the analysis of the conservation and function of vertebrate genomes.

9. Study the impact of COVID-19 on fertility.

Altogether, these research lines address the interconnections between key cell biology processes, such as meiosis, and how these are involved in the origin of mammalian infertility and genomic disorders.  Thus, these studies may help to better diagnose human infertility as well as, in the long term, they may aid the establishment of personalized medical strategies to revert male infertility in humans. Moreover, we expect that our results will provide the basis for the detection and isolation of therapeutic targets in complex human disorders and aid the design of future directional treatments.

Head of the Group:

Roig Navarro, Ignasi
Ruiz-Herrera Moreno, Aurora

Members:

Investigador en formació (Màster): López Panadès, Maria
Investigador predoctoral en formació (PhD): Alvarez Gonzalez, Lucia
Investigador predoctoral en formació (PhD): González Rodelas, Laura
Investigador predoctoral en formació (PhD): Madrid Sandín, Cristina
Investigador predoctoral en formació (PhD): Marín Gual, Laia
Investigador predoctoral en formació (PhD): Marín García, Cristina
Investigador predoctoral en formació (PhD): Nikou , Nikoleta
Investigador predoctoral en formació (PhD): Pujol Infantes, Gala

2020

The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice. Martínez-Marchal A, Huang Y, Guillot-Ferriols MT, Ferrer-Roda M, Guixé A, Garcia-Caldés M, Roig I. PLoS Genet. 2020 Nov 18;16(11):e1009067.

Meiotic Executioner Genes Protect the Y from Extinction. P. D. Waters and A. Ruiz-Herrera. Trends in Genetics 36(10):728-738, 2020. 

Cas9 in Human Embryos: On Target but No Repair. Hoffmann ER, Roig I. Cell. 2020 Dec 10;183(6):1464-1466.

Whole genome sequencing identifies Allelic Ratio Distortion in sperm involving genes related to spermatogenesis in a swine model. M. Godia, J. Casellas, A. Ruiz-Herrera, J.E. Rodríguez-Gil., A. Castelló, A. Sanchez,  A. Clop. DNA Research 27 (5), dsaa019, 2020.

Chromosomal differentiation in genetically isolated populations of the marsh-specialist Crocidura suaveolens (Mammalia: Soricidae). F. Garcia, L. Biedma, J. Calzada, J. Román, A. Lozano, F. Cortes, J. A. Godoy, A. Ruiz-Herrera. Genes, 11, 270, 2020.

2019

The PSMA8 subunit of the spermatoproteasome is essential for proper meiotic exit and mouse fertility. Gómez-H L, Felipe-Medina N, Condezo YB, Garcia-Valiente R, Ramos I, Suja JA, Barbero JL, Roig I, Sánchez-Martín M, de Rooij DG, Llano E, Pendas AM. PLoS Genet. 2019 Aug 22;15(8):e1008316.

ATR function is indispensable to allow proper mammalian follicle development. Pacheco S, Maldonado-Linares A, Garcia-Caldés M, Roig I. Chromosoma. 2019 Sep;128(3):489-500.

Three-dimensional genomic structure and cohesin occupancy correlates with transcriptional activity during spermatogenesis. C. Vara, A. Paytuví-Gallart, Y. Cuartero, F. Le Dily, F. Garcia, J.Salvà-Castro, L.Gómez-H, E. Julià, C. Moutinho, R. Aiese-Cigliano, W. Sanseverino, O. Fornas, A.M. Pendàs, H.Heyn, P. D. Waters, M. A. Marti-Renom, A. Ruiz-Herrera. Cell Reports, 28(2):352-367.e9, 2019

PRDM9 diversity at fine geographical scale in wild house mice reveals contrasting evolutionary patterns of the zinc finger domain in continental versus island populations. C. Vara, L. Capilla, L. Ferretti, A. Ledda, R.A. Sanchéz-Guillén, S.I. Gabriel, G. Albert-Lizandra, B. Florit-Sabater, J. Bello-Rodríguez, J. Ventura, J.B. Searle, M.L. Mathias, A. Ruiz-Herrera. Mol Biol Evol 36(8):1686-1700, 2019.

Per-Nucleus crossover covariation and implications for evolution. S. Wang, C. Veller, F. Sun, A. Ruiz-Herrera, Y. Shang, H. Liu, T. Hassold, D. Zickler, Z. Chen, N. Kleckner, L. Zhang. Cell 177: 1-13, 2019.

Centromeric domains and recombination frequency in horse spermatocytes.E. Cappelletti, F.M. Piras, C. Badiale, M. Bambi, C. Vara, A. Ruiz-Herrera, E. Giulotto. Scientific Reports, 9(1), 15800, 2019.

Chromosomics: bridging the gap between genomes and chromosomes. J. E. Deakin, S. Potter, R. O’Neill, A. Ruiz-Herrera, M. B. Cioffi, M. Eldridge, K. Fukui, J. Graves, D. Griffin, F. Grutzner, L. Kratochvil, I. Miura, M. Rovastos, K. Srikulnath, E. Wapstra, T. Ezaz. Genes, 10, 627, 2019.

2018

H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells. Testa E, Nardozi D, Antinozzi C, Faieta M, Di Cecca S, Caggiano C, Fukuda T, Bonanno E, Zhenkun L, Maldonado A, Roig I, Di Giacomo M, Barchi M. J Cell Sci. 2018 Mar 20;131(6):jcs214411.

ATR is a multifunctional regulator of male mouse meiosis. Widger A, Mahadevaiah SK, Lange J, ElInati E, Zohren J, Hirota T, Pacheco S, Maldonado-Linares A, Stanzione M, Ojarikre O, Maciulyte V, de Rooij DG, Tóth A, Roig I, Keeney S, Turner JMA. Nat Commun. 2018 Jul 5;9(1):2621.

ATR is required to complete meiotic recombination in mice. Pacheco S, Maldonado-Linares A, Marcet-Ortega M, Rojas C, Martínez-Marchal A, Fuentes-Lazaro J, Lange J, Jasin M, Keeney S, Fernández-Capetillo O, Garcia-Caldés M, Roig I. Nat Commun. 2018 Jul 5;9(1):2622.

Shu complex SWS1-SWSAP1 promotes early steps in mouse meiotic recombination. Abreu CM, Prakash R, Romanienko PJ, Roig I, Keeney S, Jasin M. Nat Commun. 2018 Oct 10;9(1):3961.

2017

Recombination correlates with synaptonemal complex length and chromatin loop size in ruminants - insights into mammalian meiotic chromosomal organization. A. Ruiz-Herrera, M. Vozdova, J. Fernández, H. Sebestova, L. Capilla, J. Frohlich, A. Hernández-Marsal, T.J. Robinson, J. Sipek, J. Rubes. Chromosoma, 126(5):615-631, 2017.

Validation, population analysis and origin of inversions between independently assembled human genomes. D. Vicente-Salvador, M. Puig, M. Gayà-Vidal, D. Izquierdo, A. Martínez-Fundichely, A. Ruiz-Herrera, X. Estivill, C. Aguado, J. I. Lucas-Lledó, M. Cáceres. Human Molecular Genetics, 26 (3): 567-581, 2017.

p53 and TAp63 participate in the recombination-dependent pachytene arrest in mouse spermatocytes. Marcet-Ortega M, Pacheco S, Martínez-Marchal A, Castillo H, Flores E, Jasin M, Keeney S, Roig I. PLoS Genet. 2017 Jun 15;13(6):e1006845.

2016

Meiotic recombination in mammals: a toolbox for evolution. L. Capilla, M. Garcia-Caldés, A. Ruiz-Herrera. Cytogenetics and Genome Research, 150(1):1-16, 2016.

Comparative analysis of rodent genomes reveals evolutionary signatures of genome reshuffling.L. Capilla, R.A. Sánchez-Guillén, M. Farré, R. Malinverni, J. Ventura, D. Larkin, A. Ruiz-Herrera. Genome Biology and Evolution, 8(12):3703-3717, 2016.

Extreme genomic erosion in the highly endangered Iberian lynx. F. Abascal, T. Alioto, F. Cruz, A. Corvelo, J.L. Villanueva-Cañas, A. Vlasova, M. Marcet-Houben, B. Martínez-Cruz, P. Prieto, J. Yu Cheng , V. Quesada, B. Lorente-Galdos, G. Li , F. García, J.L. Rodríguez, L. Frias, P. Ribeca, F. Câmara , E. Lowy, L. Cozzuto, I. Erb, M.L. Tress, M. Rubio-Camarillo, S. Capella-Gutiérrez, J.L. Rodriguez-Alés, J.Ruiz-Orera, F. Reverter, M. Casas-Marce, L. Soriano, J. Rodríguez-Arango, X.S. Puente, S. Derdak, B. Galán, J. Blanc, M. Gut, J. Quilez, M. Andrés-Nieto, T. Mailund, W.J. Murphy, C. Notredame, G. Roma, T. Gabaldón, M.M. Albà, C. López-Otín, A. Ruiz-Herrera, T. Marques-Bonet, A. Valencia, I. Gut, J.L. García, R. Guigó, J.A. Godoy. Genome Biology 17(1):251, 2016.

Meiotic behaviour of evolutionary sex-autosome translocations in six bovid species. M. Vozdova, A. Ruiz-Herrera, J. Fernández, H. Cernohorska, J. Frohlich, H. Sebestova, S. Kubickova, J. Vahala, J. Rubes. Chromosome Research 24(3):325-38, 2016.

Telomere homeostasis in mammalian germ cells: a review. R. Reig-Viader, M. Garcia-Caldés, A. Ruiz-Herrera. Chromosoma 125(2):337-51, 2016.

The Time Scale of Recombination Rate Evolution in Great Apes.L.S. Stevison, A.E. Woerner, J.M. Kidd, J.L. Kelley, K.R. Veeramah, K.F. McManus, Great Ape Genome Project (incl. A. Ruiz-Herrera), C.D. Bustamante, M.F. Hammer, J.D. Wall. Mol Biol Evol 33(4):928-45, 2016.

2015

Strong artificial selection in domestic mammals did not result in an increased recombination rate. Muñoz-Fuentes V, Marcet-Ortega M, Alkorta-Aranburu G, Linde Forsberg C, Morrell JM, Manzano-Piedras E, Söderberg A, Daniel K, Villalba A, Toth A, Di Rienzo A, Roig I, Vilà C. Mol Biol Evol. 2015 Feb;32(2):510-23.

The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes. Pacheco S, Marcet-Ortega M, Lange J, Jasin M, Keeney S, Roig I. PLoS Genet. 2015 Mar 13;11(3):e1005017.

CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination. Marjanović M, Sánchez-Huertas C, Terré B, Gómez R, Scheel JF, Pacheco S, Knobel PA, Martínez-Marchal A, Aivio S, Palenzuela L, Wolfrum U, McKinnon PJ, Suja JA, Roig I, Costanzo V, Lüders J, Stracker TH. Nat Commun. 2015 Jul 9;6:7676.

Extreme selective sweeps independently targeted the X chromosomes of the great apes. K. Nam, K. Munch, A. Hobolth, J.Y. Dutheil, K.R. Veeramah, A.E. Woerner, M.F. Hammer, Great Ape Genome Diversity Project (incl. A. Ruiz-Herrera), T. Mailund, M.H. Schierup. Proc Natl Acad Sci U S A 112(20):6413-8, 2015.

An integrative breakage model for genome architecture, reshuffling and evolution.M. Farré, T.J. Robinson, A. Ruiz-Herrera. Bioessays 37(5):479-88, 2015.

On the origin of Robertsonian fusions in nature: evidence of telomere shortening in wild house mice. R.A. Sánchez-Guillén, L. Capilla, R. Reig-Viader, M. Martínez-Plana, C. Pardo-Camacho, M. Andrés-Nieto, J. Ventura, A. Ruiz-Herrera. J Evol Biol 28(1):241-9, 2015. doi: 10.1111/jeb.12568.

Targeted SNP selection for improving the anchoring of the melon (Cucumis melo L.) scaffold genome assembly. J. Argyris, A. Ruiz-Herrera, P. Madriz, W. Sanseverino, J. Morata, M. Pujol, S. Ramos-Onsins, J. Garcia-Mas. BMC Genomics 16(1):4, 2015. doi: 10.1186/s12864-014-1196-3.

2014

Telomere homeostasis is compromised in spermatocytes from patients with idiopathic infertility. R. Reig-Viader, L. Capilla, M. Vila-Cejudo, R. Buscá, B. Anguita, M. Garcia-Caldés, A. Ruiz-Herrera. Fertility and Sterility 102(3):728-738, 2014. doi: 10.1016/j.fertnstert.2014.06.005.

Unravelling the effect of genome structural changes on genetic recombination in the rhesus macaque: implications for the adaptative role of inversions. A. Ullastres, M. Farre, L. Capilla, A. Ruiz-Herrera. BMC Genomics 15(1):530, 2014. (IF= 4.04, Q1 Genetics and Heredity) doi: 10.1186/1471-2164-15-530.

Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic backgound. L. Capilla, N. Medarde, A. Alemany-Schmidt, M. Oliver-Bonet, J. Ventura, A. Ruiz-Herrera. Proc R Soc B 281(1786): 20140297, 2014.

Telomeric Repeat-Containing RNA (TERRA) and Telomerase Are Components of Telomeres During Mammalian Gametogenesis. R. Reig-Viader, M. Vila-Cejudo, V. Vitelli, E. Giulotto, M. Garcia-Caldés, A. Ruiz-Herrera.. Biology of Reproduction 90(5)103:1-13, 2014

2013

Great ape genetic diversity and population history. J. Prado-Martinez, P. H. Sudmant, J. M. Kidd, H. Li, J. L. Kelley, B. Lorente-Galdos, K. R. Veeramah, A. Woerner, T. D. O’Connor, G. Santpere, A. Cagan, C. Theunert, F. Casals, H.  Laayouni, K. Munch, A. Hobolth, A. E. Halager, M. Malig, J. Hernandez-Rodriguez, I. Hernando-Herraez, K. Prüfer, M. Pybus, L. Johnstone, M. Lachmann, C. Alkan, D. Twigg, N. Petit, C. Baker, F. Hormozdiari, M. Fernandez-Callejo, M. Dabad, M. L. Wilson, L. Stevison, C. Camprubí, T. Carvalho, A. Ruiz-Herrera, L. Vives, M. Mele, T.Abello, I. Kondova, R. E. Bontrop, A. Pusey, F. Lankester, J. A. Kiyang, R. A. Berg, E. Lonsdorf, S. Myers, M. Ventura, P. Gagneux, D. Comas, H. Siegismund, J. Blanc, L. Agueda-Calpena, M. Gut, L. Fulton, S. A. Tishkoff, J. C. Mullikin, R. K. Wilson, I. G. Gut, M. K. Gonder, O. A. Ryder, B. H. Hahn, A. Navarro, J. M. Akey, J. Bertranpetit, D. Reich, T. Mailund, M. H. Schierup, C. Hvilsom, A. M. Andrés, J. Wall, C. D. Bustamante, M. Hammer, E. E. Eichler, T. Marques-Bonet. Nature 99(7459):471-5, 2013.

Rates and patterns of great ape retrotransposition. Hormozdiari F, Konkel MK, Prado-Martinez J, Chiatante G, Herraez IH, Walker JA, Nelson B, Alkan C, Sudmant PH, Huddleston J, Catacchio CR, Ko A, Malig M, Baker C; Great Ape Genome Project (incl. A. Ruiz-Herrera), Marques-Bonet T, Ventura M, Batzer MA, Eichler EE. Proc Natl Acad Sci U S A 110(33):13457-62, 2013.

Insights into the mechanisms that affect meiotic recombination rates and crossover interference in eutherian mammals.   J. Segura, L. Ferretti, S. Ramos-Onsins, L. Capilla, M. Farré, F. Reis, M. Oliver-Bonet, H. Fernández-Bellon, T.J. Robinson, M. Garcia-Caldés, A. Ruiz-Herrera. Proc R Soc B 280 (1771): 1471-2954, 2013.

Presence of an extra chromosome alters meiotic double-stranded break-repair dynamics and MLH1 foci distribution in human oocytes. Robles P, Roig I, Garcia R, Brieño-Enríquez M, Martin M, Cabero Ll, Toran N, Garcia Caldes M. Chromosoma 2013 Mar;122(1-2):93-102.

The ATM signaling network in development and disease. Stracker TH, Roig I, Knobel PA, Marjanovic M. Front Genet  2013;4:37. doi: 10.3389/fgene.2013.00037. Epub 2013 Mar 25.

Recombination rates and chromosomal reorganizations between human and chimpanzee genomes - a new twist in the chromosomal speciation theory. M. Farré, D. Micheletti, A. Ruiz-Herrera. Mol Biol Evol 30(4):853-64, 2013.

Telomeric repeat-containing RNA and telomerase in human fetal oocytes. R. Reig-Viader, M. A. Brieño-Enríquez, N. Toran, Ll. Cabero, L. Khoriauli, E. Giulotto, M. Garcia-Caldés, A. Ruiz-Herrera. Human Reprod 28(2):414-22, 2013.

This group receives financial support from the following sources:

• Ministerio de Economía y Competitividad (MINECO)
• European Union's Fondo Europeo de Desarrollo Regional (FEDER)