The origins and evolution of the p53 family of genes

Abstract

A common ancestor to the three p53 family members of human genes p53, p63, and p73 is first detected in the evolution of modern-day sea anemones, in which both structurally and functionally it acts to protect the germ line from genomic instabilities in response to stresses. This p63/p73 common ancestor gene is found in almost all invertebrates and first duplicates to produce a p53 gene and a p63/p73 ancestor in cartilaginous fish. Bony fish contain all three genes, p53, p63, and p73, and the functions of these three transcription factors diversify in the higher vertebrates. Thus, this gene family has preserved its structural features and functional activities for over one billion years of evolution.

Figure 1.

Consensus phylogenetic tree and evidence of p53 family genes, reconstructed from Ensembl database, release 54, and NCBI taxonomy database. Tree branches are proportional to the genome-wide nucleotide substitution rates for jawed vertebrates (euteleostomi), but are qualitative for more primitive species. Evidence for p53 family genes was either extracted from Ensembl database or manually verified using BLAST (for the most recent assemblies available*) (Altschul et al. 1990; Hubbard et al. 2009; Sayers et al. 2009). Evidence for p53 family genes in clams comes from gene isolation by C. Walker and others (Kelley et al. 2001; Cox et al. 2003)

Figure 2.

Scenario of the p53 family gene evolution. The earliest indication of p53 family genes dates back to invertebrates and unicellular choanoflagellae. Aside from independent gene duplications, such as in sea anemone or mosquitos, the earliest indication for mammalian gene splitting dates back to cartilaginous fishes, with tentative orthologs visible in elephant sharks, and all three mammalian paralogs appearing in bony fishes.