Patterns of sequence conservation at termini of long terminal repeat (LTR) retrotransposons and DNA transposons in the human genome: lessons from phage Mu

Abstract

Long terminal repeat (LTR) retrotransposons and DNA transposons are transposable elements (TEs) that perform cleavage and transfer at precise DNA positions. Here, we present statistical analyses of sequences found at the termini of precise TEs in the human genome. The results show that the terminal di- and trinucleotides of these TEs are highly conserved. 5'TG...CA3' occurs most frequently at the termini of LTR retrotransposons, while 5'CAG...CTG3' occurs most frequently in DNA transposons. Interestingly, these sequences are the most flexible base pair steps in DNA. Both the sequence preference and the degree of conservation of each position within the human LTR dinucleotide termini are remarkably similar to those experimentally demonstrated in transposable phage Mu. We discuss the significance of these observations and their implication for the function of terminal residues in the transposition of precise TEs.

Figure 1

Classes of TE-derived interspersed repeats, their copy number and fraction in the human genome (3). LTRs and IRs are indicated by shaded boxes.

Figure 2

(Opposite) Analysis of terminal dinucleotide steps of human LTRs. (A) Display of pattern in aligned consensus sequences at 5′ ends of human LTRs. The illustration was generated by WebLogo using 243 human LTR consensus sequences from Repbase Update. (B) Display of hierarchical clustering of human LTRs taken from MySQL tables (see Materials and Methods). The dendrogram and color image were generated as described in the text. Each human LTR is represented by a single row, and each different terminal dinucleotide sequence is represented by a single column; of the 32 columns, the left 16 are for the 5′ end and the right 16 for the 3′ end. The brightness of the red color indicates the frequency of the given dinucleotide sequence in the multiple copies of each element. Two major red columns are evident for each terminus. (C) Magnified image of the top part of (B) showing six different groups of human LTRs based on patterns of terminal dinucleotide conservation. The number of elements belonging to each group is indicated in brackets. The two most frequent patterns are indicated at the top. The average sequence frequencies of the conservation pattern in each group is indicated at the bottom, where 5′ and 3′ ends of the highest frequency pattern are included in a shaded box. (D) Graph representing the degree of consensus sequence conservation for terminal base positions in each group of human LTRs.

Figure 3

Analysis of terminal trinucleotide steps of human DNA transposons. (A) WebLogo-generated pattern of aligned consensus sequences at 5′ ends of 113 human DNA transposons. (B) Display of hierarchical clustering of human DNA transposons taken from MySQL tables (see Materials and Methods). There are a total 128 columns, the left 64 columns for the 5′ end and the right 64 for the 3′ end. The two most frequent trinucleotide sequences for both termini of the majority group (Group 15) are marked on the bottom. (C) Graph representing the degree of consensus sequence conservation for terminal base positions in each group of human DNA transposons.