Retroelements: a driving force generating genetic novelties in the human and mouse genome

• Grant number: 18/15579-8
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• Start date: May 01, 2019
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Pedro Alexandre Favoretto Galante
• Grantee: Pedro Alexandre Favoretto Galante
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Associated researchers: Anamaria Aranha Camargo ; Fabiana Bettoni ; Luiz Penalva ; Maria Isabel Alves de Souza Waddington Achatz ; Paula Fontes Asprino
• Associated research grant: 12/24731-1 - Retrocopies: origins, polymorphism and somatic variations, AP.JP
• Associated research grant(s): 20/06091-1 - Analyses of genetic variants determining the infection and evolution course of COVID-19 in young adults, AP.R
• Associated scholarship(s): 24/00078-4 - A comprehensive investigation of the interrelationship between retrocopies and cancer, BP.PD; 22/12192-0 - A systematic investigation of coding genes retrocopies activities in primates and rodents., BP.PD; 21/07329-4 - A systematic investigation of coding genes retrocopies activities in primates and rodents, BP.PD; + associated scholarships 21/04773-0 - A comprehensive investigation of the interrelationship between retrocopies and Câncer, BP.PD; 20/08992-6 - Intragenic retrocopies and its host genes, an expression inter relationship to be uncovered in tumors, BP.IC; 20/02413-4 - Intragenic retrocopies as a source of novel protein domains in humans, BP.DD - associated scholarships

Abstract

The origin of new gene regions is a preponderant factor in the evolution of several species. Retrocopies (gene duplicates generated from mRNAs) have been classified as non-functional since 1980s. However, it is currently accepted that this type of gene duplication is one of the main driving forces in generating genetic novelties in many species. In humans and mice, have been identified ~8000 and ~7200 retrocopies (RTC), respectively. However, many of them still remain understudied. Only dozens of RTC have been described as functional (retrogenes) in human and mouse. Here, we aim to perform a comprehensive study focusing on the functional characterization of all RTCs found in the human and mouse genome. To perform this, we will use robust computational methods, sequence conservation and several "omics" data, as well as in-house experimental validations focused on answering functional aspects of RTC. We will develop the project on four main lines: i) we will evaluate the fixed RTC potentially creating novel genic regions (encoding or not) in human and mouse. ii) we will evaluate the polymorphic RTC creating novel genic regions in the human population; iii) In tumors, we will evaluate the occurrence of abnormalities in gene expression involving retrocopies; iv) we will also develop and provide a web based platform capable of classifying RTCs into (potentially) functional or not. In the end, we strongly believe that we will contribute to elucidating the functional role of these genic duplicates, which have most of their features still neglected or as anecdotal in the literature. More broadly, this JP-2 will push the growing and establishment of research in bioinformatics, genomics and cancer in my group and in collaborating groups. (AU)

Scientific publications

(15)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GUARDIA, GABRIELA D. A.; CORREA, BRUNA R.; ARAUJO, PATRICIA ROSA; QIAO, MEI; BURNS, SUZANNE; PENALVA, LUIZ O. F.; GALANTE, PEDRO A. F.. Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles. NPJ GENOMIC MEDICINE, v. 5, n. 1, JAN 16 2020. (18/15579-8, 13/07159-5, 17/19541-2, 13/25483-4)

MILLER, THIAGO L. A.; REGO, FERNANDA ORPINELLI; BUZZO, JOSE LEONEL L.; GALANTE, PEDRO A. F.. sideRETRO: a pipeline for identifying somatic and polymorphic insertions of processed pseudogenes or retrocopies. Bioinformatics, v. 37, n. 3, p. 419-421, FEB 1 2021. (15/25020-0, 12/24731-1, 18/15579-8)

BARONI, MIRELLA; GUARDIA, GABRIELA D. A.; LEI, XIUFEN; KOSTI, ADAM; QIAO, MEI; LANDRY, TESHA; MAU, KARL; GALANTE, PEDRO A. F.; PENALVA, LUIZ O. F.. The RNA-Binding Protein Musashi1 Regulates a Network of Cell Cycle Genes in Group 4 Medulloblastoma. CELLS, v. 11, n. 1, JAN 2022. (17/19541-2, 18/15579-8)

KOSTI, ADAM; CHIOU, JENNIFER; GUARDIA, GABRIELA D. A.; LEI, XIUFEN; BALINDA, HENRIETTE; LANDRY, TESHA; LU, XIYUAN; QIAO, MEI; GILBERT, ANDREA; BRENNER, ANDREW; et al. ELF4 is a critical component of a miRNA-transcription factor network and is a bridge regulator of glioblastoma receptor signaling and lipid dynamics. NEURO-ONCOLOGY, v. N/A, p. 12-pg., 2022-07-21. (17/19541-2, 18/15579-8)

DOUILLARD, VENCESLAS; SILVA, NAYANE DOS SANTOS BRITO; BOURGUIBA-HACHEMI, SONIA; NASLAVSKY, MICHEL S.; SCLIAR, MARILIA O.; DUARTE, YEDA A. O.; ZATZ, MAYANA; PASSOS-BUENO, MARIA RITA; LIMOU, SOPHIE; GOURRAUD, PIERRE-ANTOINE; et al. Optimal population-specific HLA imputation with dimension reduction. HLA, v. 103, n. 1, p. 14-pg., 2023-11-11. (12/24731-1, 15/25020-0, 14/50931-3, 13/08028-1, 17/19223-0, 18/15579-8, 13/17084-2, 20/02413-4, 14/50649-6)

DE SOUZA, ANACLETO SILVA; DE FREITAS AMORIM, VITOR MARTINS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FILIPE F.; ULRICH, HENNING; GALANTE, PEDRO A. F.; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Perspective for Emerging More Transmissible and Vaccine-Resistant Strains. Viruses-Basel, v. 14, n. 4, p. 21-pg., 2022-04-01. (18/07366-4, 20/06091-1, 19/00195-2, 16/09047-8, 20/14158-9, 20/04680-0, 17/18246-7, 17/19541-2, 18/15579-8)

DE SOUZA, ANACLETO SILVA; AMORIM, VITOR MARTINS DE FREITAS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FELIPE R. C.; DOS SANTOS, FILIPE F.; DE SOUZA, ROBSON FRANCISCO; JUVENAL, GUILHERME DE ARAUJO; HUANG, YIHUA; GE, PINGJU; JIANG, YINAN; et al. Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2. ACS OMEGA, v. 7, n. 35, p. 10-pg., 2022-08-24. (20/06091-1, 17/18246-7, 17/19541-2, 20/04680-0, 19/00195-2, 16/09047-8, 18/15579-8, 18/07366-4, 20/14158-9)

BARBALHO DE MELLO, LUIS EDUARDO; RIBEIRO CARNEIRO, THAISE NAYANE; ARAUJO, ALINE NEVES; ALVES, CAMILA XAVIER; FAVORETTO GALANTE, PEDRO ALEXANDRE; BUZATTO, VANESSA CANDIOTTI; DE ALMEIDA, MARIA DAS GRACAS; VERMEULEN-SERPA, KARINA MARQUES; DE LIMA VALE, SANCHA HELENA; DE PINTO PAIVA, FERNANDO JOSE; et al. Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing. ENDOCRINE CONNECTIONS, v. 11, n. 1, p. 16-pg., 2022-01-01. (18/15579-8, 14/06570-6, 18/23497-1)

NASLAVSKY, MICHEL S.; SCLIAR, MARILIA O.; YAMAMOTO, GUILHERME L.; WANG, JAQUELINE YU TING; ZVERINOVA, STEPANKA; KARP, TATIANA; NUNES, KELLY; MAGLIOCCO CERONI, JOSE RICARDO; DE CARVALHO, DIEGO LIMA; DA SILVA SIMOES, CARLOS EDUARDO; et al. Whole-genome sequencing of 1,171 elderly admixed individuals from Sao Paulo, Brazil. NATURE COMMUNICATIONS, v. 13, n. 1, p. 11-pg., 2022-03-04. (12/24731-1, 20/02413-4, 14/50649-6, 13/08028-1, 18/15579-8, 15/25020-0, 17/19223-0, 13/17084-2)

SEQUEIRA BARREIRO, RODRIGO ARAUJO; SABBAGA, JORGE; ROSSI, BENEDITO M.; ACHATZ, MARIA ISABEL W.; BETTONI, FABIANA; CAMARGO, ANAMARIA A.; ASPRINO, PAULA F.; GALANTE, PEDRO A. F.. Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis. JOURNAL OF PATHOLOGY, v. 256, n. 2, NOV 2021. (18/15579-8, 20/06091-1, 19/04927-8)

DOS SANTOS, FELIPE R. C.; GUARDIA, GABRIELA D. A.; DOS SANTOS, FILIPE F.; OHARA, DANIEL T.; GALANTE, PEDRO A. F.. Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis. NAR CANCER, v. 3, n. 2, p. 15-pg., 2021-06-01. (17/18246-7, 18/15579-8, 17/19541-2, 17/17974-9)

BREUNIG, KIRA; LEI, XUIFEN; MONTALBANO, MAURO; GUARDIA, GABRIELA D. A.; OSTADRAHIMI, SHIVA; ALERS, VICTORIA; KOSTI, ADAM; CHIOU, JENNIFER; KLEIN, NICOLE; VINAROV, CORINA; et al. SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis. eLIFE, v. 13, p. 37-pg., 2025-02-12. (17/19541-2, 18/15579-8)

MICALI, DANILO; ROSA, JOICE SANTOS; OTA, VANESSA KIYOMI; MERCURI, RAFAEL LUIZ VIEIRA; SPINDOLA, LETICIA MARIA; BUGIGA, AMANDA VICTORIA GOMES; KAJITANI, GUSTAVO SATORU; MILANI, ANA CAROLINA COELHO; SALMERON, CAMILLA; SILVA, IVALDO; et al. hsa-miR-582-3p in umbilical cord blood is negatively associated with maternal exposure to childhood maltreatment. Epigenomics, v. N/A, p. 14-pg., 2024-10-09. (19/21612-0, 18/15579-8, 20/02413-4)

CONCEICAO, HELENA B.; MERCURI, RAFAEL L., V; DE CASTRO, MATHEUS P. M.; OHARA, DANIEL T.; GUARDIA, GABRIELA D. A.; GALANTE, PEDRO A. F.. RCPedia: a global resource for studying and exploring retrocopies in diverse species. Bioinformatics, v. 40, n. 9, p. 5-pg., 2024-09-10. (24/00078-4, 18/15579-8, 20/02413-4, 18/13613-4, 17/19541-2)

BARREIRO, RODRIGO A. S.; GUARDIA, GABRIELA D. A.; MELISO, FABIANA M.; LEI, XIUFEN; LI, WEI-QING; SAVIO, ANDRE; FELLERMEYER, MARTIN; CONCEICAO, HELENA B.; MERCURI, RAFAEL L. V.; LANDRY, TESHA; et al. The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes. RNA BIOLOGY, v. 20, n. 1, p. 12-pg., 2023-12-31. (18/15579-8)