All animals begin life as a single-celled zygote, but become multicellular throu

Question

All animals begin life as a single-celled zygote, but become multicellular through development. The increase in number of cells must come from an increased number of mitotic divisions and this in turn may increase the risk of developing cancer. However, when looking at animals of varying body size, scientists find no correlation between body size and cancer incidence. In fact, some large bodied animals such as elephants (Loxodonta africana and Elephas maxima) have very low rates of cancer. It has recently been reported that elephants have at least 20 copies of the TP53 gene that makes the protein p53, whereas humans only have one copy (2 alleles).

Describe the process whereby elephants probably acquired so many copies of the TP53 gene? Hint: it also may have been responsible for so many copies of CYP, RAS and BRC1 genes.

How is the possession of extra TP53 genes and adaptation for large, long-lived organisms? In your answer, identify which cancer hallmark this may be an adaptation against.

Explanation / Answer

a. Elephants acquire extra copies of TP53, which are often known as retrogenes. Retrogenes are protein coding copies of other genes that originate through a process known as gene retroposition. However, new copies of these TP53 appear to have lost the ability to encode a complete p53 protein , and thus represent pseudogenes more appropriately retrogenes. In this way elephants probably acquired so many copies of the TP53 gene.

b. Cancer is less prevalent in elephants than in humans, in part because the giant animals have more copies of a gene that suppresses tumor growth.In contrast with human, elephants get at least 20 copies of TP53 from each parent, which may explain their low rate of cancer. The increase number of TP53 occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Normally TP53 retrogenes (TP53RTGs) are transcribed and then translated. These TP53RTGs do not appear to directly function as transcription factors, rather they contribute to enhanced the sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes.

Related Questions

Navigate

• Browse (All)
• Browse A
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.