Ask a Scientist Staff

Ruth, NJ, US

We are currently studying gene switches and natural selection in my class. My students and I do not fully understand what actually turns the switches on and off. For example, in the stickleback fish. What caused the gene to be turned off. Is it something environmental?

Ask a Scientist Staff

The term “genetic switch” describes DNA sequences that regulate the activity of a gene. These sequences are outside of the protein-coding region of the gene. The switches are turned on and off only when specific binding proteins are present. There is an excellent interactive activity on the BioInteractive website that illustrates the concept; to view it go to

www.hhmi.org/biointeractive/evolution/Gene_Switches/01.html

In eukaryotes, the enzyme RNA polymerase II transcribes protein-coding genes. It requires other proteins, referred to as general transcription factors, which assemble at the promoter of a gene before transcription can begin. In addition to these general transcription factors, cells have regulatory proteins that bind “genetic switches,” turning gene expression on or off. Any one gene can have multiple genetic switches, which means that the gene can be on or off in a variety of cell types, and even at different times in development, depending on the regulatory proteins that bind its switches. If there’s no regulatory protein present in a cell, the corresponding switch doesn’t get turned on (or off) and the gene’s not expressed (or is!).

So what determines what regulatory proteins are present or not in a cell? During development, a whole series of switches get an egg to develop into a segmented organism with nose to tail differences; once you have a switch defining dorsal and ventral regions, for example, those tissues can make specific regulatory proteins found only dorsally or ventrally, which in turn will only activate genes in dorsal or ventral tissues. Post-development, the expression of regulatory proteins can be somewhat dependent on environmental factors or the signals that cells send back and forth to each other, like hormones (reach lots of tissues), or modulatory factors that reach fewer tissues.

In the case of sticklebacks, a mutation in a “genetic switch” is responsible for a change in the body plan of the fish which has played a role in the fish evolution.

Stickleback fishes occur in two forms: a freshwater form and a marine form. The marine sticklebacks have long spines that are part of their pelvis, which serve as a defense against predators in the ocean waters. The freshwater sticklebacks living in shallow lake waters have shorter spines or no spines at all compared to their marine counterparts. On the lake bottom long pelvic spines are not needed for protection and can in fact be a liability.

The evolution of distinct stickleback populations is recent. After the last ice age, some marine sticklebacks became stranded in the lakes that formed from the melting glaciers. These sticklebacks had to adapt to a new freshwater environment and repeatedly diverged into the short- and long-spined populations.

Scientists have discovered that one gene, called Pitx1, is primarily responsible for the growth of the pelvic spines during fish development. Pitx1 is produced in many parts of the growing fish embryo, including the jaw, pituitary, thymus, lateral sensory organs and pelvis. The protein produced by Pitx1 controls the expression of other genes and has counterparts in other animals.

The expression of Pitx1 in various parts of the body is regulated by different genetic switches. You can imagine that the regulatory region of Pitx1 contains distinct genetic switches for expression in the pelvis, thymus, and so on. (In the scientific literature these genetic switches are referred to as “tissue-specific enhancers.”)

Scientists have found that several populations of freshwater, bottom-dwelling sticklebacks have a mutation in the genetic switch of Pitx1 that guides pelvic expression. This mutation prevents the binding of the regulatory protein (or proteins) needed for Pitx1 to be expressed in the pelvis. As a result, Pitx1 is no longer expressed in the pelvic region of the growing embryo but it is still expressed in other body regions.

02/10/12 06:49