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<p>Abstract</p> <p>Background</p> <p><it>PL10 </it>homologs exist in a wide range of eukaryotes from yeast, plants to animals. They share a DEAD motif and belong to the DEAD-box polypeptide 3 (<it>DDX3</it>) subfamily with a major role in RNA metabolism. The lineage-specific expression patterns and various genomic structures and locations of <it>PL10 </it>homologs indicate these homologs have an interesting evolutionary history.</p> <p>Results</p> <p>Phylogenetic analyses revealed that, in addition to the sex chromosome-linked <it>PL10 </it>homologs, <it>DDX3X </it>and <it>DDX3Y</it>, a single autosomal <it>PL10 </it>putative homologous sequence is present in each genome of the studied non-rodent eutheria. These autosomal homologous sequences originated from the retroposition of <it>DDX3X </it>but were pseudogenized during the evolution. In rodents, besides <it>Ddx3x </it>and <it>Ddx3y</it>, we found not only <it>Pl10 </it>but another autosomal homologous region, both of which also originated from the <it>Ddx3x </it>retroposition. These retropositions occurred after the divergence of eutheria and opossum. In contrast, an additional X putative homologous sequence was detected in primates and originated from the transposition of <it>DDX3Y</it>. The evolution of <it>PL10 </it>homologs was under positive selection and the elevated Ka/Ks ratios were observed in the eutherian lineages for <it>DDX3Y </it>but not <it>PL10 </it>and <it>DDX3X</it>, suggesting relaxed selective constraints on <it>DDX3Y</it>. Contrary to the highly conserved domains, several sites with relaxed selective constraints flanking the domains in the mammalian <it>PL10 </it>homologs may play roles in enhancing the gene function in a lineage-specific manner.</p> <p>Conclusion</p> <p>The eutherian <it>DDX3X/DDX3Y </it>in the X/Y-added region originated from the translocation of the ancient <it>PL10 </it>ortholog on the ancestral autosome, whereas the eutherian <it>PL10 </it>was retroposed from <it>DDX3X</it>. In addition to the functional <it>PL10</it>/<it>DDX3X</it>/<it>DDX3Y</it>, conserved homologous regions on the autosomes and X chromosome are present. The autosomal homologs were also derived from <it>DDX3X</it>, whereas the additional X-homologs were derived from <it>DDX3Y</it>. These homologs were apparently pseudogenized but may still be active transcriptionally. The evolution of <it>PL10 </it>homologs was positively selected.</p>