Identification of multiple TAR DNA binding protein retropseudogene lineages during the evolution of primates

Abstract

The TAR DNA Binding Protein (TARDBP) gene has become relevant after the discovery of its several pathogenic mutations. The lack of evolutionary history is in contrast to the amount of studies found in the literature. This study investigated the evolutionary dynamics associated with the retrotransposition of the TARDBP gene in primates. We identified novel retropseudogenes that likely originated in the ancestors of anthropoids, catarrhines, and lemuriformes, i.e. the strepsirrhine clade that inhabit Madagascar. We also found species-specific retropseudogenes in the Philippine tarsier, Bolivian squirrel monkey, capuchin monkey and vervet. The identification of a retropseudocopy of the TARDBP gene overlapping a lncRNA that is potentially expressed opens a new avenue to investigate TARDBP gene regulation, especially in the context of TARDBP associated pathologies.

Figure 1

Maximum likelihood tree showing sister group relationships between the functional copy of TARDBP and primate retropseudogenes. Numbers on the nodes correspond to support values, i.e. the confidence of each node. TARDBP sequences from the African elephant (Loxodonta africana), blue whale (Balaenoptera musculus) and red fox (Vulpes vulpes) were used as outgroups (not shown). The scale denotes substitutions per site and colors represent lineages. The pink lineage represents the TARDBP functional copy. Synteny information is provided for each lineage at the right side of the figure.

Figure 2

Graphical representation of the alignment between the lncRNA (ENSG00000225057)(x-axis) and the retropseudogene (y-axis) sequences of humans located on chromosome 2. Light blue and light yellow vertical rectangles denote exons and introns, respectively. The black diagonal line indicates a locally alignable region of high sequence identity.

Figure 3

Time calibrated primate phylogeny showing the origin of the different retropseudogene lineages depicted in Fig. 1. Triangles represent the diversification of each primate group, where the left side angle defines the ancestor of each group. Numbers on the triangles correspond to retropseudogenes originated within a particular group of primates. Silhouette images were obtained from PhyloPic (http://phylopic.org/). Divergence times were obtained from timetree (http://www.timetree.org/)..