Fig 1.
Prion protein nucleotide sequences based phylogenetic tree compiled using BEAST software.
1146 different nucleotide sequences from 901 different mammalian species were used to perform the analysis as described. Coloured clusters represent different mammalian orders, consistent with the latest species trees. The mammalian orders tend to maintain their clusterization in the PRNP gene tree, albeit with some exceptions such as the clusterization of most Afrotheria (A major clade of mammals with African origins, including elephants, manatees, aardvarks, and tenrecs) with Primates and Dermoptera (order of colugos or “flying lemurs,” gliding mammals from Southeast Asia), as well as the nesting of Lipotyphla (an obsolete order formerly used to group insectivorous mammals such as hedgehogs, shrews, and moles, now largely replaced by Eulipotyphla) within the Chiroptera (bats) species.
Fig 2.
A standard phylogenetic tree of species
(A) compared to the tree obtained in this study using the PRNP gene (B). Both trees illustrate orders or higher organisational clades whenever possible. The tree on the left (A) represents a classical mammalian evolution tree (modified from Springer 2004 [43]), whereas the tree on the right (B) displays the results obtained in this study. Classifications above the order level are represented to the right of the tree, while preceding classifications are shown at the corresponding nodes. In the tree obtained in this study (B) the colours correspond to those used in the example tree (A) for the same higher clades, facilitating comparison between the two. While species belonging to the same order tend to be clustered together in the PRNP gene tree, higher classifications show less conservation. However, the trees exhibit substantial similarity, and the few differences presented could offer insight into PRNP evolution.
Fig 3.
Evaluation of the genetic variations identified in the branch separations of the PRNP tree according to its characteristics.
The 4 types of DNA variants found in the most relevant splits of the PRNP gene tree were evaluated. The most often occurring changes among PRNP sequences are insertions and deletions of trinucleotide microsatellites, mostly around the OR region. Next are transitions which are more common than transversions, as described in the literature. Others refers to changes where both transitions and transversions have occurred in one position.
Fig 4.
Analysis of the rs1799990 locus in the human PRNP gene compared to other primate’s species included in this study.
The variant, highlighted in green, appears only in the human sequence. We have not been able to find it in any other species among all Primates sequenced. The A to G variant causes a non-synonymous change of methionine to valine. Other synonymous changes are highlighted in blue, whereas non-synonymous changes around this region have been highlighted in yellow.
Fig 5.
Analysis of rs1799990-G allele frequency in prehistoric human PRNP.
The rs1799990 variant has been present in human populations as early as the Neolithic with a G-allele frequency of 0.2, which increased to a frequency similar to that of current H. sapiens populations (0.3) from the Chalcolithic period and has been maintained around this level throughout the Bronze and Iron Ages until the present.