The p53 gene family in vertebrates: Evolutionary considerations

Abstract

The origin of the p53 gene family predates multicellular life since TP53 members of this gene family have been found in unicellular eukaryotes. In invertebrates one or two genes attributable to a TP53‐like or TP63/73‐like gene are present. The radiation into three genes, TP53, TP63, and TP73, has been reported as a vertebrate invention. TP53 is considered the “guardian of the genome” given its role in protecting cells against the DNA damage and cellular stressors. TP63 and TP73 play a role in epithelial development and neurogenesis, respectively. The evolution of the p53 gene family has been the subject of considerable analyses even if several questions remain still open. In this study we addressed the evolutionary history of the p53 gene family in vertebrates performing an extended microsyntenic investigation coupled with a phylogenetic analysis, together with protein domain organization and structure assessment. On the basis of our results we discussed a possible evolutionary scenario according to which a TP53/63/73 ancestor form gave rise to the current TP53 and a TP63/73 form, which in turn independently duplicated into two genes in agnathe and gnathostome lineages.

Characterization of p53 Family Homologs in Evolutionary Remote Branches of Holozoa

“…The N-terminal transactivation domain first appeared in Metazoa, as shown by Aberg et al [52]. The tetramerization motif is too Recently, two paralogs from Monosiga brevicollis and three paralogs from Salpingoeca rosetta were mentioned in a paper dealing with the p53 gene family in vertebrates [54]. These results support our data from non-Metazoan analyses.…”

“…Based on these recent data we have updated the p53 family ancestral tree and show the closest evolutionary branches where p53 family homologs are not present ( Figure 5). Recently, two paralogs from Monosiga brevicollis and three paralogs from Salpingoeca rosetta were mentioned in a paper dealing with the p53 gene family in vertebrates [54]. These results support our data from non-Metazoan analyses.…”

The Elephant Evolved p53 Isoforms that Escape MDM2-Mediated Repression and Cancer

“…Interestingly, the glutamic acid (E), asparagine (N), tryptophan (W), and tyrosine (Y) residues are highly conserved in disordered proteins as they play crucial role in forming protein–protein interfaces ( Brown et al 2010 ). As such, it emerges that cross-species studies, like our pilot study presented here, on genetic variations of p53 can lead to several novel insights into altered structural and functional outcomes of p53 action ( Wang et al 2007 ; Lu et al 2009 ; Belyi et al 2010 ; Joerger et al 2014 ; Coffill et al 2016 ; Bartas et al 2019 ; Biscotti et al 2019 ; Fischer 2019 ). Derived discoveries will in turn lead to novel, testable hypotheses concerning clinical aspects of p53 with links to the development of drug-resistance or cancer progression ( Somarelli, Gardner, et al 2020 ; Salomao et al 2021 ).…”

Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?

“…For example, the products of the TP53 and the PTEN genes, and the enzymes that maintain telomere length, are highly conserved mechanisms that suppress tumor formation across many different species. [108][109][110][111][112][113][114][115][116] Replicative senescence is another widespread, primordial mechanism that seems to protect animal species against longevity-associated somatic modifications. 117,118 In most cells, senescence programs are activated upon reaching a predetermined number of replication events, as well as by somatic mutation events, and many genes involved in regulation of senescence have been directly implicated in tumor suppression.…”