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In my Intro. to Biochemistry course, we have been studying cancer. The professor has pointed out that tumor suppressor genes are "recessive" while proto-oncogenes are "dominant". Since only one mutation is necessary to turn a proto-oncogene into an oncogene; while two are needed for the malfunctioning of tumor suppressor genes, why is this not the other way around (i.e. tumor suppressor genes dominant; proto-oncogenes recessive)?

All help is greatly appreciated.

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    $\begingroup$ Just for the semantic, a gene is not dominance or recessive. An allele at a given gene (or locus to be more general) can be dominant or recessive in its relationship to another allele. So what you mean by dominant gene, you mean that the wild type allele is dominant over the mutant allele (and vice-versa for what you call recessive genes). $\endgroup$
    – Remi.b
    Nov 17, 2017 at 22:41
  • $\begingroup$ "proto-oncogenes" $\endgroup$
    – user37894
    Nov 17, 2017 at 23:05
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    $\begingroup$ why would they not be, why has a mechanism to sickle cell not evolved a regulator gene, in both cases it becasue the necessary mutations has not occurred. Dominance is a side effect of how the gene and its products function, it is not affect by the whether the allele is deleterious or not. $\endgroup$
    – John
    Nov 18, 2017 at 6:12

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I was typing out an explanation, but then realized that this text book does a much better job:

Lodish et al. 2000. Section 24.2: Proto-Oncogenes and Tumor-Suppressor Genes in Molecular Cell Biology 4ed. WH Freeman

Proto-Oncogene:

Conversion, or activation, of a proto-oncogene into an oncogene generally involves a gain-of-function mutation. At least three mechanisms can produce oncogenes from the corresponding proto-oncogenes.

  • Point mutations in a proto-oncogene that result in a constitutively acting protein product
  • Localized reduplication (gene amplification) of a DNA segment that includes a proto-oncogene, leading to overexpression of the encoded protein
  • Chromosomal translocation that brings a growth-regulatory gene under the control of a different promoter and that causes inappropriate expression of the gene

An oncogene formed by the first mechanism encodes an oncoprotein that differs slightly from the normal protein encoded by the corresponding proto-oncogene. In contrast, the latter two mechanisms generate oncogenes whose protein products are identical with the normal proteins; their oncogenic effect is due to their being expressed at higher-than-normal levels or in cells where they normally are not expressed. However they arise, the gain-of-function mutations that convert proto-oncogenes to oncogenes act dominantly; that is, mutation in only one of the two alleles is sufficient for induction of cancer.

Tumour Supressor Gene:

Tumor-suppressor genes generally encode proteins that in one way or another inhibit cell proliferation.... Since generally one copy of a tumor-suppressor gene suffices to control cell proliferation, both alleles of a tumor-suppressor gene must be lost or inactivated in order to promote tumor development. Thus oncogenic loss-of-function mutations in tumor-suppressor genes act recessively.

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  • $\begingroup$ A clarification that would improve this answer: As in Remi.b's comment, the alleles are recessive, not the genes. In the context of cancer, the key point is that cancer-causing alleles of tumor suppressor genes are recessive, not the genes themselves. Often loss-of-function alleles are recessive, because a single healthy copy is capable of performing most of the function. $\endgroup$
    – Bryan Krause ♦
    Nov 18, 2017 at 0:19
  • $\begingroup$ Thank you! This clarifies things a lot. I am really sorry about the way I wrote my question -- I am aware that what we call recessive or dominant is an allele, not a gene as a whole. If I understand correctly then, in the context of cancer we say that the allele that for instance undergoes a loss-of-function mutation in a TSG is recessive (as canadianer quoted), but then... would the wild-type allele for a TSG be dominant with respect to the mutated allele? (TSG = tumor-suppressor gene). Thanks a lot to everyone! $\endgroup$
    – Bee
    Nov 19, 2017 at 8:11
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    $\begingroup$ @Bee You’re welcome! Yes, it would be dominant in relation to the the loss-of-function allele since its activity alone is sufficient for the wild-type phenotype. $\endgroup$
    – canadianer
    Nov 19, 2017 at 8:19
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Note that while this is generally true - there is also a phenomenon of haploinsufficiency with some tumour suppressors. That means losing one copy is enough to permit tumour development.

See http://www.sciencedirect.com/science/article/pii/S0304419X04000022?via%3Dihub

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