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1.
Genome Res ; 34(3): 426-440, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38621828

RESUMO

Genome structural variations within species are rare. How selective constraints preserve gene order and chromosome structure is a central question in evolutionary biology that remains unsolved. Our sequencing of several genomes of the appendicularian tunicate Oikopleura dioica around the globe reveals extreme genome scrambling caused by thousands of chromosomal rearrangements, although showing no obvious morphological differences between these animals. The breakpoint accumulation rate is an order of magnitude higher than in ascidian tunicates, nematodes, Drosophila, or mammals. Chromosome arms and sex-specific regions appear to be the primary unit of macrosynteny conservation. At the microsyntenic level, scrambling did not preserve operon structures, suggesting an absence of selective pressure to maintain them. The uncoupling of the genome scrambling with morphological conservation in O. dioica suggests the presence of previously unnoticed cryptic species and provides a new biological system that challenges our previous vision of speciation in which similar animals always share similar genome structures.


Assuntos
Genoma , Urocordados , Animais , Urocordados/genética , Urocordados/classificação , Evolução Molecular , Feminino , Filogenia , Masculino , Sintenia
2.
Science ; 374(6567): eabb3420, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34709885

RESUMO

Immune cells identify and destroy damaged cells to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report that the cell-cycle inhibitor p21 places cells under immunosurveillance to establish a biological timer mechanism that controls cell fate. p21 activates retinoblastoma protein (Rb)­dependent transcription at select gene promoters to generate a complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes the chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if cells normalize p21 within 4 days, but if p21 induction persists, they polarize toward an M1 phenotype and lymphocytes mount a cytotoxic T cell response to eliminate target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress.


Assuntos
Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Vigilância Imunológica , Animais , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Quimiocinas CXC/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Genes ras , Hepatócitos/imunologia , Hepatócitos/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína do Retinoblastoma/metabolismo , Estresse Fisiológico , Linfócitos T Citotóxicos/imunologia , Transcrição Gênica
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