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首页> 外文期刊>Genes and Nutrition >Identifying evolutionarily conserved genes in the dietary restriction response using bioinformatics and subsequent testing in Caenorhabditis elegans
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Identifying evolutionarily conserved genes in the dietary restriction response using bioinformatics and subsequent testing in Caenorhabditis elegans

机译：使用生物信息学在饮食限制反应中鉴定进化保守基因，并在秀丽隐杆线虫中进行后续测试

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Dietary restriction (DR) increases life span, health span and resistance to stress in a wide range of organisms. Work from a large number of laboratories has revealed evolutionarily conserved mechanisms that mediate the DR response. Here, we analyzed the genome-wide gene expression profiles of Caenorhabditis elegans under DR versus ad libitum conditions. Using the Ortho2ExpressMatrix tool, we searched for C. elegans orthologs of mouse genes that have been shown to be differentially expressed under DR conditions in nearly 600 experiments. Based on our bioinformatic approaches, we obtained 189 DR-responsive genes, and 45 of these are highly conserved from worm to man. Subsequent testing of sixteen genes that are up-regulated under DR identified eight genes that abolish the DR-induced resistance to heat stress in C. elegans. Further analyses revealed that fkb-4, dod-22 and ikb-1 genes also abolish increased life span in response to DR. The identified genes that are necessary for the DR response are sensitive to certain stress signals such as metabolic perturbances (dod-22, fkb-4 and nhr-85), DNA damage (ikb-1), heat shock (hsp-12.6) and cancer-like overgrowth (prk-2 and tsp-15). We propose that most of the DR-responsive genes identified are components of the recently discovered cellular surveillance-activated detoxification and defenses pathway, which is, among others, important for the survival of organisms in times of food deprivation.
机译：饮食限制（DR）可以延长多种生物的寿命，健康寿命和抵抗压力的能力。大量实验室的工作揭示了介导DR反应的进化保守机制。在这里，我们分析了秀丽隐杆线虫在DR与随意条件下的全基因组基因表达谱。使用Ortho2ExpressMatrix工具，我们搜索了将近600个实验中在DR条件下差异表达的小鼠基因的秀丽隐杆线虫直系同源基因。根据我们的生物信息学方法，我们获得了189个DR反应基因，其中45个从蠕虫到人都是高度保守的。随后对16个在DR下上调的基因进行了测试，确定了8个基因，这些基因消除了DR诱导的秀丽隐杆线虫对热胁迫的抗性。进一步的分析表明，fkb-4，dod-22和ikb-1基因也废除了响应DR的寿命增加。已确定的DR反应必需基因对某些应激信号敏感，例如代谢紊乱（dod-22，fkb-4和nhr-85），DNA损伤（ikb-1），热休克（hsp-12.6）和癌样过度生长（prk-2和tsp-15）。我们提出，鉴定出的大多数DR响应基因都是最近发现的细胞监视激活的排毒和防御途径的组成部分，这对食物匮乏时生物的生存至关重要。

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