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Células com genoma minimalista sintético submetido a divisão celular normal

Células with fully artificial synthesized genoma were reported first in 2010 from which a minimalistic genoma cell was derived that apresentaram morfologia anormal na divisão celular. A recente adição de um grupo de genes a esta célula minimalista restaurou a divisão celular normal

As células são as unidades estruturais e funcionais básicas da vida, uma teoria proposta por Schleiden e Schwann em 1839. Desde então, os cientistas têm se interessado em entender as funções celulares tentando decifrar o código genético completamente para entender como a célula cresce e se divide para dar origem a mais células de um tipo semelhante. Com o advento de DNA sequencing, it has been possible to decode the sequence of the genoma thereby making an attempt to understand the cellular processes to comprehend the basis of life. In the year 1984, Morowitz proposed the study of mycoplasmas, the simplest células capable of autonomous growth, for understanding the basic principles of life.  

Since then, several attempts have been made to reduce the genoma size to a minimalistic number giving rise to a cell that is capable of performing all the basic cellular functions. The experiments first led to the chemical synthesis of Mycoplasma mycoides genoma of 1079 Kb in the year 2010 and was named as JCVI-syn1.0. Further deletions made in JCVI-syn1.0 by Hutchinson III et al. (1) gave rise to JCVI-syn3.0 in 2016 that had a genoma size of 531 Kb with 473 genes and had a doubling time of 180 minutes, albeit having an abnormal morphology upon cell division. It still had 149 genes with unknown biological functions, suggesting the presence of still undiscovered elements that are essential for life. However, JCVI-syn3.0 provides a platform for investigating and understanding life functions by applying the principles of whole-genoma design. 

Recently, on March 29 2021, Pelletier and colleagues (2) used JCVI syn3.0 to understand the genes required for cell division and morphology by introducing 19 genes in the genoma of JCVI syn3.0, giving rise to JCVI syn3.0A that has a morphology similar to JCVI syn1.0. upon cell division. 7 of these 19 genes, includes two known cell division genes and 4 genes encoding membrane-associated proteins of unknown function, which together restored the phenotype similar to that of JCVI-syn1.0. This result suggests the polygenic nature of cell division and morphology in a genomically minimal cell.  

Given the fact that the JCVI syn3.0 is capable of surviving and multiplying based on its minimalistic genoma, it can be used as a model organism to create different cell types having varied functions that can be beneficial to humans and the environment. For example, one can introduce genes that lead to dissolution of plastics so that the new organism made can be used for degradation of plastics in a biological manner. Similarly, once can envisage adding genes pertaining to photosynthesis in JCVI syn3.0 making it amenable to use carbon dioxide from the atmosphere thereby reducing its levels and help in reducing global warming, a major climatic issue facing mankind. However, such experiments have to be treated with utmost caution to ensure that we do not release a super organism in the environment that is difficult to control once it is released. 

Nonetheless, the idea of having a cell with minimalistic genome and its biological manipulation can lead to creation of varied cell types with diverse functions capable of solving major issues facing mankind and its ultimate survival. However, there is a distinction between creation of a fully synthetic cell versus creation of a functionally synthetic genoma. An ideal completely synthetic artificial cell would consist of a synthesized genoma along with synthesized cytoplasmic components, a feat which scientists would love to achieve sooner than later in the coming years as the technological advances reach its peak.  

O recente desenvolvimento pode ser um trampolim para a criação de uma célula totalmente sintética, capaz de crescer e se dividir. 

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Referências:  

  1. Hutchison III C, Chuang R., et al 2016. Design and synthesis of a minimal bacterial genomaCiência 25 Março de 2016: Vol. 351, problema 6280, aad6253 
    DOI: https://doi.org/10.1126/science.aad6253   
  1. Pelletier JF, Sun L., et al 2021. Requisitos genéticos para a divisão celular em uma célula genomicamente mínima. Célula. Publicado: 29 de março de 2021. DOI: https://doi.org/10.1016/j.cell.2021.03.008 

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Rajeev Soni
Rajeev Sonihttps://www.RajeevSoni.org/
Dr. Rajeev Soni (ID ORCID: 0000-0001-7126-5864) é Ph.D. em Biotecnologia pela Universidade de Cambridge, Reino Unido e tem 25 anos de experiência trabalhando em todo o mundo em vários institutos e multinacionais, como The Scripps Research Institute, Novartis, Novozymes, Ranbaxy, Biocon, Biomerieux e como investigador principal no US Naval Research Lab na descoberta de medicamentos, diagnóstico molecular, expressão de proteínas, fabricação biológica e desenvolvimento de negócios.

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