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p53 is an important tumor suppressor gene. Around 50% of cancers are associated with loss of function in p53.

Humans have only two copies of p53 in their genome (one on each homologous chromosome). Elephants on the other hand have 20 or so copies of p53, and they also rarely die of cancer.

From an evolutionary point of view, I find it very curious that humans (and most other animals, I guess) haven't evolved more copies of p53 on their genome. Duplications of genes happen all the time, so there is variation in copy number for natural selection to work upon.

Are there known to be evolutionary forces at play (e.g. positive or balancing selection) which determine the differences in number copies of this gene between species?

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  • $\begingroup$ Natural selection can only work on variability already present. Since there is only one copy of p53, I would suggest that perhaps a duplication of this gene is incredibly rare to start with, and even if we accept the premise that having an extra copy of p53 would prevent certain cancers, why would that measurably affect reproductive fitness? Remember that a part of natural selection involves surviving to pass on beneficial gene variants, or on the other hand not surviving to pass on detrimental ones. $\endgroup$
    – natb
    Aug 31 at 16:13
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    $\begingroup$ I think this could easily be reframed into a very interesting question along the the lines of 'Do evolutionary forces determine the number of copies of the p53 gene in different species'. It seems a shame to be closed. $\endgroup$
    – user438383
    Aug 31 at 17:45
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    $\begingroup$ elifesciences.org/articles/11994 $\endgroup$
    – user438383
    Aug 31 at 17:50
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    $\begingroup$ With the upvotes and edits I think there's too much community support for this question to have my unilateral close stand, so I've reopened. I'd hope that answers to the question would focus on the evolution of copy number of these gene in other species, and upregulation experiments in humans, rather than rehashing what we have already answered in biology.stackexchange.com/questions/35532/… $\endgroup$
    – Bryan Krause
    Aug 31 at 21:38
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    $\begingroup$ I agree with user438383, but think this needs more work on your part. In particular, a summary with references of what is known about variation of p53 copy number (and cancer prevalence) throughout animals seems needed. I think you should show that duplication of p53 is relatively easy and that increasing p53 copy number does suppress cancer (or at least correlates for more than one exceptional species). As a start I would read about this on wikipedia, in the paper linked above, and at Nature. $\endgroup$
    – tyersome
    Aug 31 at 21:48

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