A novel web-based TinT application and the chronology of the Primate Alu retroposon activity

Abstract

Background: DNA sequences afford access to the evolutionary pathways of life. Particularly mobile elements that constantly co-evolve in genomes encrypt recent and ancient information of their host's history. In mammals there is an extraordinarily abundant activity of mobile elements that occurs in a dynamic succession of active families, subfamilies, types, and subtypes of retroposed elements. The high frequency of retroposons in mammals implies that, by chance, such elements also insert into each other. While inactive elements are no longer able to retropose, active elements retropose by chance into other active and inactive elements. Thousands of such directional, element-in-element insertions are found in present-day genomes. To help analyze these events, we developed a computational algorithm (Transpositions in Transpositions, or TinT) that examines the different frequencies of nested transpositions and reconstructs the chronological order of retroposon activities.

Results: By examining the different frequencies of such nested transpositions, the TinT application reconstructs the chronological order of retroposon activities. We use such activity patterns as a comparative tool to (1) delineate the historical rise and fall of retroposons and their relations to each other, (2) understand the retroposon-induced complexity of recent genomes, and (3) find selective informative homoplasy-free markers of phylogeny. The efficiency of the new application is demonstrated by applying it to dimeric Alu Short INterspersed Elements (SINE) to derive a complete chronology of such elements in primates.

Conclusion: The user-friendly, web-based TinT interface presented here affords an easy, automated screening for nested transpositions from genome assemblies or trace data, assembles them in a frequency-matrix, and schematically displays their chronological activity history.

Figure 1

Interpretation of RepeatMasker outfiles and TinT information. Schematic representation of the nested insertion of an AluSq element (coordinates in red) into an AluJb element (coordinates in blue). The framed area of the RepeatMasker outfile contains the information analyzed by the TinT application and the default parameters. The five characteristics used for extracting unambiguous nested clusters are as follows: (1) fragmented/inserted elements must be located at the same query sequence, (2) for stringent conditions, the element indices for the two parts of the fragmented element must be identical and the index for the nested element must be higher than this; for relaxed conditions the same class of fragmented element parts is sufficient, (3) the minimum size of all elements (starting/ending coordinates) must be 20 nt or more, (4) the fragmented parts of the host element must both be in the same orientation, and (5) the non-overlapping host elements should preferably be larger than 50 nt, but at least ≥ 19 nt with an overlap of no more than 35 nt (starting/end-position consensus).

Figure 2

Results of the TinT analysis for different Alu dimers in primates. The lower part of each panel represents the data matrix derived from the RepeatMasker outfile. Subtypes listed across the top represent host elements; those listed along the left side are the inserted elements. The copy numbers of Alu elements are indicated in the last column and the sums of nested insertions for both hosts and inserted elements are shown across the bottom and to the right, respectively. The upper parts of each panel present a graphical display of the chronological activities of the elements sorted by the peak of each activity. The center of each oval represents the maximum of each activity period; the ends of each oval encompass 75%, the vertical lines 95%, and the ends of each line 99% of the probable activity period range. Elements within grey boxes are taxon-specific elements. A relative time scale is shown below. TinT profiles for (A) Homo sapiens, (B) Macaca mulatta, (C) Callithrix jacchus, (D) Tarsius syrichta, and (E) Microcebus murinus.

Figure 3

TinT activity patterns and species evolution. Schematic representation of the phylogenetic relationships of the five major primate groups: Strepsirrhini (represented by Microcebus murinus), Tarsiiformes (represented by Tarsius syrichta), Platyrrhini (represented by Callithrix jacchus), Cercopithecoidea (represented by Macaca mulatta), and Hominoidea (represented by Homo sapiens). The dating is taken from [25,26]. AluJo elements were active at the divergence of Strepsirrhines and AluJb at the divergence of Tarsiiformes. The main activity of AluS elements occurred around the evolution of Anthropoidea; AluY elements arose on the lineage leading to Cercopithecoidea and are still active in Catarrhini, including Macaca mulatta and Homo sapiens. Group-specific Alu elements are indicated at terminal branches (L = AluL, La = AluLa, Mim = AluMim; Ta = AluTa; YR = AluYR).