Caretaker Gene - Mutations in Context

Mutations in Context

It has been proposed that mutations in gatekeeper genes could, to an extent, offer a sort of selective advantage to the individual in which the change occurs. This is because cells with these mutations are able to replicate at a faster rate than nearby cells. This is known as "increased somatic fitness". Caretaker genes, on the other hand, confer selective disadvantage because the result is inherently decreased cellular success. However, increased somatic fitness could also arise from a mutation in a caretaker gene if mutations in tumor suppressor genes increase the net reproductive rate of the cell.

Although mutations in gatekeeper genes may lead to the same result as those of caretaker genes, namely cancer, the transcripts that gatekeeper genes encode are significantly different from those encoded by caretaker genes.

In many cases, gatekeeper genes encode a system of checks and balances that monitor cell division and death. In cases of tissue damage, for example, gatekeeper genes would ensure that balance of cell growth over cellular death remains in check. In the presence of competent gatekeeper genes, mutations of other genes would not lead to on-going growth imbalances.

Whether or not mutations in these genes confer beneficial or deleterious effects to the animal depends partially on the environmental context in which these changes occur, a context encoded by the landscaper genes. For example, tissues of the skin and colon reside in compartments of cells that rarely mix with one another. These tissues are replenished by stem cells. Mutations that occur within these cell lineages remain confined to the compartment in which they reside, increasing the future risk of cancer. This is also protective, however, because the cancer will remain confined to that specific area, rather than invading the rest of the body, a phenomenon known as metastasis.

In areas of the body compartmentalized into small subsets of cells, mutations that lead to cancer most often begin with caretaker genes. On the other hand, cancer progression in non-compartmentalized or large cell populations may be a result of initial mutations in gatekeepers.

These delineations offer a suggestion why different types of tissue within the body progress to cancer by differing mechanisms.