The Evolution of LINE-1 in Vertebrates

Abstract

The abundance and diversity of the LINE-1 (L1) retrotransposon differ greatly among vertebrates. Mammalian genomes contain hundreds of thousands L1s that have accumulated since the origin of mammals. A single group of very similar elements is active at a time in mammals, thus a single lineage of active families has evolved in this group. In contrast, non-mammalian genomes (fish, amphibians, reptiles) harbor a large diversity of concurrently transposing families, which are all represented by very small number of recently inserted copies. Why the pattern of diversity and abundance of L1 is so different among vertebrates remains unknown. To address this issue, we performed a detailed analysis of the evolution of active L1 in 14 mammals and in 3 non-mammalian vertebrate model species. We examined the evolution of base composition and codon bias, the general structure, and the evolution of the different domains of L1 (5′UTR, ORF1, ORF2, 3′UTR). L1s differ substantially in length, base composition, and structure among vertebrates. The most variation is found in the 5′UTR, which is longer in amniotes, and in the ORF1, which tend to evolve faster in mammals. The highly divergent L1 families of lizard, frog, and fish share species-specific features suggesting that they are subjected to the same functional constraints imposed by their host. The relative conservation of the 5′UTR and ORF1 in non-mammalian vertebrates suggests that the repression of transposition by the host does not act in a sequence-specific manner and did not result in an arms race, as is observed in mammals.

Fig. 1.—

Pattern of evolution of L1 families in mammals and non-mammals. The phylogenies are ML trees based on the data of Khan et al. (2006) and Novick et al. (2009). The number of copy for each family is indicated in bold. (A) This phylogeny represents the evolution of L1 families in human and demonstrates the ladder-like mode of evolution typical of mammals. (B) This phylogeny is based on lizard L1 families (Novick et al. 2009) and is typical of non-mammalian vertebrates (reptiles, amphibians and fish).

Fig. 2.—

(A) Typical structure of human and murine rodents full-length L1 elements (CCD = Coiled-coil domain; RRM = RNA recognition motif; CTD = C-terminal domain; EN = Endonuclease domain; RT = Reverse transcriptase domain). (B) Schematic structure of full-length L1 families in mammals, lizard, frog and zebrafish.

Fig. 3.—

Maximum likelihood phylogeny of L1 families based on ORF2 amino acid sequences.

Fig. 4.—

Evolution of the mammalian IGR. The figure suggests that the ancestor of mammals had an IGR that was lost after the split between afrotheria (elephant and hyrax) and other mammals and that an IGR was regained in pig. The branch-lengths on the phylogeny are not up to scale.

Fig. 5.—

Base composition at the three codon positions for ORF1 and ORF2.

Fig. 6.—

Frequency of amino acids in ORF1 and ORF2 for mammals, lizard, frog, and zebrafish.

Fig. 7.—

Dotmatcher analysis of the horse, elephant, dog, and cow 5′UTR against themselves. Note the long tandem duplication in horse and elephant and the repeats rich region of the dog and cow 5′UTRs (framed with blue boxes).

Fig. 8.—

Alignment of the 5′ termini of L1 in mammals (A), lizard clade 1 (B), lizard clade 2 (C), frog (D), and zebrafish (E). The length of the alignments varies among groups since the length of the 5′ termini that could be aligned differed.

Fig. 9.—

Amino acid alignment of the RRM and CTD. The two RRMs are boxed in blue, the amino acids forming the stabilizing salt bridge are indicated with orange arrows, the residues providing RNA-binding side chains are indicated with green arrows, and the PDPK docking sites are boxed in red and the PP1 docking site in purple.

Fig. 10.—

Schematic structure of the CCD of ORF1. The structure of the coiled coils is based on the analysis with a 28 residues window width.

Fig. 11.—

(A) Schematic structure of the IGR showing the position of the predicted IRES. (B) RNA structure of the predicted IRES of the elephant, frog L1-15 and zebrafish L1-1A compared with the IRES of a dicistroviridae, the cripavirus-1 infecting the insect Homalodisca coagulata (GenBank accession number KT207917).