Marine stickleback fish have pelvic fins with long spines that provide protection from larger predatory fish. Some stickleback fish were trapped in lakes and have adapted to life in a different environment. Many lake populations of stickleback fish lack pelvic fins. Shapiro et al. (2004) (Nature 428:717.723) mapped the mutation associated with the loss of pelvic fins to the Pitx1 locus, a gene expressed in pelvic fins, the pituitary gland, and the jaw. However, the coding sequence of the Pitx1 gene is identical in marine and lake stickleback [Chan et al. (2010). Science 327:5963,302–305]. Moreover, when the Pitx1 coding region is deleted, the fish die with defects in the pituitary gland and the jaw, and they lack pelvic fins. Explain how a mutation near, but outside of, the coding region of Pitx1 may cause a loss of pelvic fins without pleiotropic effects on the pituitary gland and jaw.

Verified step by step guidance

1. Understand that the Pitx1 gene is expressed in multiple tissues: pelvic fins, pituitary gland, and jaw, and that mutations in the coding region affect all these tissues, causing pleiotropic effects.
2. Recognize that the coding sequence of Pitx1 is identical in both marine and lake stickleback fish, so the difference in pelvic fin development is not due to changes in the protein itself.
3. Consider that gene expression can be regulated by sequences outside the coding region, such as enhancers or promoters, which control when and where the gene is turned on.
4. Hypothesize that a mutation near but outside the Pitx1 coding region could disrupt a tissue-specific enhancer responsible for activating Pitx1 expression only in pelvic fins, without affecting its expression in the pituitary gland or jaw.
5. Conclude that this regulatory mutation would lead to loss of Pitx1 expression specifically in pelvic fins, causing their loss, while leaving Pitx1 function intact in other tissues, thus avoiding pleiotropic effects.

Key Concepts

Regulatory Mutations and Gene Expression

Mutations outside the coding region, such as in enhancers or promoters, can alter when, where, or how much a gene is expressed without changing the protein sequence. In this case, a mutation near Pitx1 may disrupt pelvic fin-specific enhancers, reducing Pitx1 expression only in pelvic fins, while leaving expression in other tissues intact.

Pleiotropy and Tissue-Specific Gene Regulation

Pleiotropy occurs when one gene influences multiple traits or tissues. Pitx1 affects pelvic fins, pituitary gland, and jaw development. Tissue-specific regulatory elements allow a gene to be expressed differently in each tissue, so mutations in specific enhancers can affect one trait without causing defects in others.

Functional Importance of Coding vs. Non-Coding Regions

The coding region of a gene determines the protein’s structure, while non-coding regions control gene expression patterns. Identical coding sequences with different phenotypes suggest that changes in non-coding regulatory DNA, rather than protein structure, underlie phenotypic differences such as loss of pelvic fins.