Análise de plasticidade das vias de senescência celular, apoptose e estabilidade genômica
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2022-06-21
Autores
Andrade, Gustavo Bortolanza de
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Universidade Estadual Paulista (Unesp)
Resumo
Os mecanismos de manutenção genômica são de suma importância para organismos eucariontes pois atuam frente a inconformidades no DNA, reparando seus danos e corrigindo possíveis erros ou até inativando ou destruindo a célula em casos extremos. Desta forma, mecanismos de manutenção genômica promovem longevidade, pois impedem que erros no DNA se acumulem e se propaguem levando a célula a se tornar um tumor. A abordagem evolutiva para estudo destas vias gênicas que agem na estabilidade genômica e na supressão tumoral ajuda a compreender suas origens e suas relações à medida que estas foram se desenvolvendo ao longo da evolução. Com o objetivo de analisar a plasticidade das vias de genes envolvidos nos mecanismos de manutenção genômica, foi utilizado o Geneplast do Bioconductor, uma ferramenta de análise, que se baseia na distribuição dos ortólogos ao longo de determinada árvore evolutiva, e infere seus valores de abundância, diversidade e plasticidade. Os dados foram fornecidos pelos bancos de dados String, e o KEGG (Kyoto Encyclopedia of Genes and Genomes). Verificou-se então os valores de abundância, diversidade e plasticidade dos genes das vias de apoptose, senescência celular e estabilidade genômica, o que revelou que o grupo de estabilidade genômica possui a maior diversidade entre os três, sendo a via com maior presença entre os organismos da árvore. Ao mesmo tempo, esse grupo possui o menor valor de abundância, o que indica que há poucos parálogos desses genes nos organismos. Por conseguinte, seus índices de plasticidade evolutiva possuem os menores valores, o que indica um grupo de genes com baixa aceitação às mutações e alterações na forma como este mecanismo funciona. Este conjunto de ortólogos é essencial tanto em organismos unicelulares, como em organismos mais complexos, o que pode explicar sua aparição antiga na árvore de eucariotos e sua presença constante e quase inalterada ao longo de toda a história evolutiva deste grupo. Por outro ângulo em relação aos ortólogos das vias de apoptose e senescência celular, notou-se que eles são estatisticamente idênticos, tanto em relação aos valores de diversidade, quanto do índice de plasticidade evolutiva, o que pode indicar que eles tiveram aparições em um mesmo ancestral comum, recentemente em comparação a via de estabilidade genômica. Porém, seus valores de abundância são distintos e maiores nos ortólogos que atuam na via de apoptose, o que indicaria que este grupo tem uma aceitação maior a alterações. Embora esta análise seja promissora, ainda há muito a se descobrir em relação à história evolutiva dos genes que atuam mantendo a estabilidade genômica, e mais análises são necessárias para inferir a origem exata destes genes assim como a influência que exercem uns sobre os outros
The mechanisms of genome maintenance are of the uttermost importance for eukaryotic organisms because they act in the face of DNA errors or nonconformities, repairing the damage and correcting occasional errors or even inactivating or destroying the cell in some extreme cases. In this way, genomic maintenance mechanisms promote longevity, as they prevent errors from accumulating and spreading, leading the cell to become a tumor. The evolutionary approach to the study of these gene pathways that act on genomic stability and tumor suppression helps to understand their origins and the development of their relationships throughout evolution. In order to analyze the plasticity of the genes pathways involved in the mechanisms of genomic maintenance, an analysis tool was used. Geneplast from the bioconductor uses the distribution of orthologs along a given evolutionary tree, to infer their abundance, diversity and plasticity values. Data were provided by the String databases, and the KEGG (Kyoto Encyclopedia of Genes and Genomes). The values of abundance, diversity and plasticity of the genes of apoptosis, cellular senescence and genomic stability pathways were then verified, revealing that the genomic stability group has the greatest diversity among the three. At the same time, this group has the lowest abundance value, which indicates that there are few paralogs of these genes in organisms. Therefore, their evolutionary plasticity indices have the lowest values, which indicates a group of genes with low acceptance for mutations and changes in its functions. This set of orthologs is essential both to unicellular organisms and in more complex organisms, which may explain its ancient appearance in the eukaryote tree and its constant and almost unchanged presence throughout the evolutionary history of this group. From another angle in relation to the orthologs of the apoptosis and cellular senescence pathways, it was noted that they are statistically identical, both in terms of diversity values and evolutionary plasticity index, which may indicate that they had appearances in the same common ancestor, recently if compared with the genomic stability pathway. However, their abundance values are higher in orthologs that act in the apoptosis pathway, which would indicate that this group has a greater acceptance of alterations. Although this analysis is promising, much remains to be discovered regarding the evolutionary history of genes that act in genome maintenance, and further analysis is needed to infer the exact origin of these genes, as well as the influence they exert on each other.
The mechanisms of genome maintenance are of the uttermost importance for eukaryotic organisms because they act in the face of DNA errors or nonconformities, repairing the damage and correcting occasional errors or even inactivating or destroying the cell in some extreme cases. In this way, genomic maintenance mechanisms promote longevity, as they prevent errors from accumulating and spreading, leading the cell to become a tumor. The evolutionary approach to the study of these gene pathways that act on genomic stability and tumor suppression helps to understand their origins and the development of their relationships throughout evolution. In order to analyze the plasticity of the genes pathways involved in the mechanisms of genomic maintenance, an analysis tool was used. Geneplast from the bioconductor uses the distribution of orthologs along a given evolutionary tree, to infer their abundance, diversity and plasticity values. Data were provided by the String databases, and the KEGG (Kyoto Encyclopedia of Genes and Genomes). The values of abundance, diversity and plasticity of the genes of apoptosis, cellular senescence and genomic stability pathways were then verified, revealing that the genomic stability group has the greatest diversity among the three. At the same time, this group has the lowest abundance value, which indicates that there are few paralogs of these genes in organisms. Therefore, their evolutionary plasticity indices have the lowest values, which indicates a group of genes with low acceptance for mutations and changes in its functions. This set of orthologs is essential both to unicellular organisms and in more complex organisms, which may explain its ancient appearance in the eukaryote tree and its constant and almost unchanged presence throughout the evolutionary history of this group. From another angle in relation to the orthologs of the apoptosis and cellular senescence pathways, it was noted that they are statistically identical, both in terms of diversity values and evolutionary plasticity index, which may indicate that they had appearances in the same common ancestor, recently if compared with the genomic stability pathway. However, their abundance values are higher in orthologs that act in the apoptosis pathway, which would indicate that this group has a greater acceptance of alterations. Although this analysis is promising, much remains to be discovered regarding the evolutionary history of genes that act in genome maintenance, and further analysis is needed to infer the exact origin of these genes, as well as the influence they exert on each other.
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Palavras-chave
Estabilidade genômica, Manutenção gênomica, Plasticidade evolutiva, Supressão tumoral