Author(s):
Brattig-Correia, Rion ; Almeida, Joana M. ; Wyrwoll, Margot Julia ; Julca, Irene ; Sobral, Daniel ; Misra, Chandra Shekhar ; Di Persio, Sara ; Guilgur, Leonardo Gastón ; Schuppe, Hans Christian ; Silva, Neide ; Prudêncio, Pedro ; Nóvoa, Ana ; Leocádio, Ana S. ; Bom, Joana ; Laurentino, Sandra ; Mallo, Moises ; Kliesch, Sabine ; Mutwil, Marek ; Rocha, Luis M. ; Tüttelmann, Frank ; Becker, Jörg D. ; Navarro-Costa, Paulo
Date: 2024
Persistent ID: http://hdl.handle.net/10362/179703
Origin: Repositório Institucional da UNL
Project/scholarship:
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMEC-AND%2F30221%2F2017/PT;
info:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FMEC-AND%2F0676%2F2021/PT;
info:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND%2F03345%2F2018%2FCP1564%2FCT0010/PT;
info:eu-repo/grantAgreement/FCT//PD%2FBD%2F114362%2F2016/PT;
Subject(s): D. melanogaster; evolutionary biology; gene expression; germ cells; human; infertility; medicine; meiosis; mouse; spermatogenesis; Neuroscience(all); Biochemistry, Genetics and Molecular Biology(all); Immunology and Microbiology(all); SDG 3 - Good Health and Well-being
Description
National Institutes of Health (1R01LM012832) National Science Foundation (Research Traineeship grant 1735095). Deutsche Forschungsgemeinschaft (329621271). Ministry of Education, Singapore (MOE2018-T2-2-053). Publisher Copyright: © 2024, Brattig-Correia, Almeida, Wyrwoll et al.
Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.
