Abstract
BackgroundpiggyBac domain (PGBD) transposons are found in organisms ranging from fungi to humans. Three domesticated piggyBac elements have been described. In the ciliates Paramecium tetraurelia and Tetrahymena thermophila, homologs known as piggyMacs excise internal eliminated sequences from germline micronuclear DNA during regeneration of the new somatic macronucleus. In primates, a PGBD3 element inserted into the Cockayne syndrome group B (CSB) gene over 43 Mya serves as an alternative 3′ terminal exon, enabling the CSB gene to generate both full length CSB and a conserved CSB-PGBD3 fusion protein that joins an N-terminal CSB domain to the C-terminal transposase domain.ResultsWe describe a fourth domesticated piggyBac element called PGBD5. We show that i) PGBD5 was first domesticated in the common ancestor of the cephalochordate Branchiostoma floridae (aka lancelet or amphioxus) and vertebrates, and is conserved in all vertebrates including lamprey but cannot be found in more basal urochordates, hemichordates, or echinoderms; ii) the lancelet, lamprey, and human PGBD5 genes are syntenic and orthologous; iii) no potentially mobile ancestral PGBD5 elements can be identified in other more deeply rooted organisms; iv) although derived from an IS4-related transposase of the RNase H clan, PGBD5 protein is unlikely to retain enzymatic activity because the catalytic DDD(D) motif is not conserved; v) PGBD5 is preferentially expressed in certain granule cell lineages of the brain and in the central nervous system based on available mouse and human in situ hybridization data, and the tissue-specificity of documented mammalian EST and mRNA clones; vi) the human PGBD5 promoter and gene region is rich in bound regulatory factors including the neuron-restrictive silencer factors NRSF/REST and CoREST, as well as SIN3, KAP1, STAT3, and CTCF; and vii) despite preferential localization within the nucleus, PGBD5 protein is unlikely to bind DNA or chromatin as neither DNase I digestion nor high salt extraction release PGBD5 from fractionated mouse brain nuclei.ConclusionsWe speculate that the neural-specific PGBD5 transposase was domesticated >500 My after cephalochordates and vertebrates split from urochordates, and that PGBD5 may have played a role in the evolution of a primitive deuterostome neural network into a centralized nervous system.
Highlights
PiggyBac domain (PGBD) transposons are found in organisms ranging from fungi to humans
We show that mouse PGBD5 is mainly nuclear and, consistent with publically available in situ hybridization and expression data, preferentially expressed in specific areas of the brain and central nervous system (CNS) that are enriched in granule cells
Human PGBD5 lacks 3 of the 4 catalytically active aspartates that are often conserved among diverse piggyBac elements, the positions of these four aspartates in a ClustalW alignment of piggyBac proteins most closely related to the active cabbage looper moth (Trichoplusia ni) transposase including human PGBD1, 2, 3, 4, and 5 [21] are highlighted in yellow
Summary
PiggyBac domain (PGBD) transposons are found in organisms ranging from fungi to humans. PiggyBacs are not the only active domesticated transposases: the RAG1/2 recombinases of the human immune system are presumably descended from an ancient Transib transposase [4,5,6,7] and, most recently, the human THAP9 gene has been found to encode a catalytically active P-element DNA transposase of as yet unknown function [8] Some domesticated transposons such as the centomere protein CENPB retain nuclear localization and specific DNA binding but have lost enzymatic function [9,10], whereas others such as SETMAR/Metnase [11,12] and the Cockayne syndrome Group B-PiggyBac domain 3 (CSB-PGBD3) fusion protein [13,14,15] retain site-specific DNA binding but gain new functions by fusion with upstream coding exons. The mouse genome lacks PGBD2, 3, and 4 homologs, but contains a modestly conserved PGBD1 suggesting introduction early in the mammalian radiation
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