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Transcriptome Study of Muscle Tissue in Nellore Cattle Divergent for Beef Quality

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Transcriptome Study of Muscle Tissue in Nellore Cattle Divergent for Beef Quality UNIVERSIDADE ESTADUAL PAULISTA - UNESP CÂMPUS DE JABOTICABAL TRANSCRIPTOME STUDY OF MUSCLE TISSUE IN NELLORE CATTLE DIVERGENT FOR BEEF QUALITY Maria Malane Magalhães Muniz Zootecnista 2020 ii UNIVERSIDADE ESTADUAL PAULISTA - UNESP CÂMPUS DE JABOTICABAL TRANSCRIPTOME STUDY OF MUSCLE TISSUE IN NELLORE CATTLE DIVERGENT FOR BEEF QUALITY Maria Malane Magalhães Muniz Orientadora: Profa. Dra. Lucia Galvão de Albuquerque Coorientadora: Dra. Larissa Fernanda Simielli Fonseca Tese apresentada à Faculdade de Ciências Agrárias e Veterinárias – Unesp, Câmpus de Jaboticabal, como parte das exigências para a obtenção do título de Doutor Genética e Melhoramento Animal 2020 iii iv v DADOS CURRICULARES DO AUTOR Maria Malane Magalhães Muniz – Nasceu em Camocim, Ceará em 19 de Outubro de 1988, filha de Lucia Maria Magalhães e Manoel Gonçalves Muniz. Iniciou sua graduação em Zootecnia na Universidade Estadual Vale do Acarau (UVA), Câmpus Central de Sobral em agosto de 2009. Durante a graduação (2009-2012) participou de projetos científicos, foi bolsista EMBRAPA e CNPq, monitora na disciplina Melhoramento Genético Animal e recebeu certificado de Mérito Acadêmico por ter obtido o primeiro lugar na apresentação de trabalhos no curso de Bacharelado em Zootecnia-UVA. Em Março de 2013, iniciou seu mestrado no programa de pós-graduação em Ciências Animais da Universidade de Brasília- UNB, onde foi bolsista CNPq. Durante o mestrado dedicou-se a estudo de associação ampla do genoma para coloração de pelagem em ovinos da raça Morada Nova, sob orientação do pesquisador Dr. Samuel Rezende Paiva, recebendo o título de mestra em Março de 2015. Foi professora (2015-2016) nos programas de gradução em Agronomia e Medicina Veterinária no Centro Universitário ICESP - Águas Claras-DF. Em agosto de 2016 iniciou o Doutorado no programa de pós-graduação em Genética e Melhoramento Animal da Universidade Estadual Paulista, Faculdade de Ciências Agrárias e Veterinárias, Câmpus de Jaboticabal (FCAV/Unesp) sob orientação do professora Dra. Lucia Galvão de Albuquerque, sendo bolsista CAPES e FAPESP. Realizou Estágio de Pesquisa no Exterior, no período de Setembro de 2018 a Março de 2020, na Universidade de Guelph, Canadá, onde desenvolveu parte do seu projeto de doutorado, sob orientação do professora Dra. Angela Cánovas. Durante o período de setembro/2018 à março/2019 obteve a Bolsa Estágio de Pesquisa no Exterior (BEPE)- FAPESP. vi “O espírito que adquirir a virtude do perdão não achará dificuldade em mais nada. Haja o que houver aconteça o que acontecer, ele saberá administrar sua vida.” Chico Xavier vii DEDICO A todos aqueles que de alguma forma contribuíram com meu progresso moral e acadêmico, principalmente a minha família que sempre estive presente. viii AGRADECIMENTOS Em primeiro lugar, agradeço sempre à Deus. Agradeço pelas inúmeras oportunidades que sempre me concedeu, por me dar forças diariamente e por iluminar meus caminhos. Ao meu mentor espiritual que está sempre ao meu lado me protegendo e me guiando no caminho do bem. À Faculdade de Ciências Agrárias e Veterinárias do Campus de Jaboticabal, especificamente ao Programa de Pós-graduação em Genética e Melhoramento Animal por essa oportunidade e os conhecimentos adquiridos. À Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) nº dos processos (#2009/16118-5, #2017/04270-3, #2017/10630-2, #2018/11154-2 e #2018/ 20026-8) por todo o suporte financeiro. O presente trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Código de Financiamento 001, agradeço pelo apoio financeiro. Graças ao apoio financeiro da FAPESP e CAPES pude dedicar-me exclusiva às atividades de pós-graduação e desenvolvido na minha tese. À minha orientadora Lucia Galvão de Albuquerque, por essa grande oportunidade e ensinamentos durante todos esses anos. Serei eternamente grata! À minha coorientadora Larissa Fernanda Simielli Fonseca pelos ensinamentos, toda ajuda e amizade durante todos esses anos. Aos membros da banca de qualificação Dra. Larissa Fernanda Simielli Fonseca, e aos Doutores Jesus Aparecido Ferro, Henrique Nunes de Oliveira, Gerardo Alves Fernandes Junior e Rafael Lara Tonussi pelas sugestões que melhoraram muito o trabalho. Aos membros da banca de defesa, as Doutoras Poliana Fernanda Giachetto a Danielly Beraldo dos Santos Silva e aos Doutores Jesus Aparecido Ferro, Daniel Guariz Pinheiro pela valiosa contribuição na defesa desta tese. À Dra. Angela Canovas por ter me orientado durante meu estágio sanduíche na Unversidade de Guelph, pelo conhecimento adquirido, pela disposição e atenção que me foi dada durante todo o período de estágio. À minha família (pais, irmãos, sobrinha, tios, primos e avós) amada e amigos por todo amor, carinho e apoio. Aos amigos do Departamento de Zootecnia, ix especialmente aos meus queridos amigos: Karla, Cíntia, Ana Fabrícia, Patricia, Danielly, Anderson, Andres, Ana Cristina, Bruna, Gabriela, Marta, Larissa, Lúcio Flávio, Rafael, Henrique, Natalia, Thaise e William. Obrigada por toda ajuda, amizade e momentos de descontração e alegria. Também agradeço a todos os queridos amigos que tive a felicidade de encontrar e conviver durante a minha estada em Jaboticabal. À Universidade de Guelph pelas oportunidades de desenvolver e aprimorar este trabalho e a todas as pessoas que de alguma forma contribuíram para a preparação do mesmo, especialmente aos queridos amigos: Stephanie, Aroa, Pablo, Samir, Giovana, Riani, Hinaya, Amelia. E a todos os amigos canadenses que me acolheram, muito obrigada por toda amizade e apoio. x ESTUDO DO TRANSCRIPTOMA DO TECIDO MUSCULAR DE BOVINOS DA RAÇA NELORE DIVERGENTES PARA CARACTERÍSTICAS DE QUALIDADE DE CARNE RESUMO - As características de qualidade de carne, por serem de difícil mensuração, raramente são contempladas em programas de melhoramento genético. Porém, é necessário conhecer sobre os genes e os mecanismos moleculares que controlam essas características, isso poderá auxiliar na avaliação de animais de forma precoce. Objetivo desse estudo foi identificar e analisar genes e isoformas de mRNA diferencialmente expressos no tecido do músculo Longissimus thoracis de bovinos da raça Nelore, fenotipicamente divergentes para características cor da carne, marmoreio e maciez da carne (avaliada através das metodologias de WBSF e MFI) usando dados de RNA-Seq. Além disso, esse estudo visa a identificação dos efeitos de variantes estruturais em “splice sites” de transcriptos diferencialmente expressos em animais fenotipicamente divergentes para as características de color e marmoreio da carne. Uma média de 37 mil transcritos foram detectados sendo expressos no músculo de bovinos Nelore. Foram identificados 40 e 28 isoformas de mRNA (p-valor < 0,001) diferencialmente expressas para os fenótipos de WBSF e MFI, respectivamente. Além disso, foram identificados sendo diferencialmente expressos os mRNAs [WBSF (SYNPO-201) e MFI (ANKRD23-202)], e entre outras isoformas de mRNA relacionadas a genes que afetam a velocidade de degradação das fibras musculares durante o processo de envelhecimento da carne, como e.g. [para WBSF (MYOT, CASQ1, TPM2, MB e SYNM) e para MFI (FGFRL1 e NEB)]. Na análise de enriquecimento, esses genes foram associados com funções biológicas relacionadas á processos oxidativos, produção de energia, contração muscular estriada, via de sinalização de HIF-1 e metabolismo de aminoácidos e derivados. Além disso, 14 e 15 isoformas de mRNA foram diferencialmente expressas (p-valor ≤ 0,001) entre os animais com alto marmorização da carne em relação ao grupo de animais com baixo marmorização, e entre o grupo de animais com coloração desejável em relação ao grupo de animais com coloração indesejável da carne, respectivamente. Entre elas foram encontrados mRNAs: COL4A2-202, RPL30-203, MAPKAPK2-204, NEURL1-201, SCL16A6-201 e JSP.1-204 que apresentaram variantes estruturais (e.g., variantes de nucleotídeo único, inserção ou exclusão) responsáveis pela a interrupção de sites de splicing nessas regiões. A análise de enriquecimento, realizada para a lista de isoformas de mRNA diferencialmente expressas para marmoreio e para coloração da carne identificou vias metabólicas comuns entre essas características, como por exemplo, a via de troca de O2/CO2 nos eritrócitos, biossíntese de tirosina e a via de degradação de fenilalanina. Possivelmente, o mecanismo de interação entre essas características dá-se através da oxidação lipídica mitocondrial que está intimamente relacionada à formação de mioglobina férrica, molécula importante para manter a cor fresca da carne vermelha. Os resultados obtidos nesse estudo mostram que as isoformas de mRNAs encontrados podem ser potenciais genes reguladores das características de maciez, coloração e marmoreio da carne bovina, as quais são características economicamente importantes para a indústria de carne. Palavras-chave: Coloração da carne, isoforma de mRNA, Marmoreio, MFI, RNA- Seq, WBSF. xi TRANSCRIPTOME STUDY OF MUSCLE TISSUE IN NELLORE CATTLE DIVERGENT FOR BEEF QUALITY ABSTRACT - The measurement of meat quality traits are costly, because of that it is rarely included in breeding programs. However, it is necessary to know about the genes and the molecular mechanisms that control these traits, this may help in the evaluation of animals at an early stage.Thus, the identification of mRNA isoforms and the associated splice variants affecting meat quality traits in Nellore cattle could allow to better understanding the genetic architecture of these complex traits. The objective
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