In gene knockout studies, scientists delete or stop expression of one gene and then check to see if that gene is required. In these studies, if a gene is critical – say for cell division then cells do not divide and the gene is termed essential, the mutations in that gene would be termed lethal and no progeny occur. Similarly, if that gene is not an essential gene then it leads to a phenotype. For e.g. if you would remove the melanin gene then you would get a albino phenotype. However, not every phenotype is observable and sometimes scientists need to put the organism in a set of conditions that would elicit that phenotype. For another example, if you were studying yeast and deleted a gene essential in say lactose metabolism then you will need to keep the yeast in lactose medium to determine whether that is essential. Another way to do these tests are called “fitness tests”. The deletion of the gene may not lead to any phenotype but when you observe the whole population then a phenotype appears. Thus, if studying the ability to form colonies was an enzyme then deletion of the enzyme would lead to a phenotype.
In single cell organism, the fitness tests show that only a minority of the genes could generate a loss-of-function phenotype. This seems illogical since many of the genes are conserved over time but it has been shown that almost every gene is required for growth under different conditions.
AK Ramani et al showed in Cell, 148:792, 2012 that “The majority of Animal genes are required for Wild Type Fitness” in a C.elegans study. The unique feature they found that when they did the fitness study of C. elegans in a single environment they found that a much higher proportion of genes were deemed essential. They did not have to change the growth conditions to elicit the phenotype as compared to unicellular organisms. Their right conjecture is that organs have a different expression pattern of genes and that each organ thus serves as a different environment for that set of genes. This also suggests that the gene networks are not robust to mutation which in unlike what had been previously thought and that small mutations may lead to major changes.
This inherent instability makes C. elegans another system for screening for drugs against cancer as proposed by SS Siddiqui (Cancer Biol Ther, 7: 856, 2008) for c-met mutations. It obviously does not have the entire complement of human genes in human organs but at least the system important for tumorogenicty may be evolutionarily conserved to find new targets for cancer therapy.
