Inference of transposable element ancestry

Most common methods for inferring transposable element (TE) evolutionary relationships are based on dividing TEs into subfamilies using shared diagnostic nucleotides. Although originally justified based on the “master gene” model of TE evolution, computational and experimental work indicates that many of the subfamilies generated by these methods contain multiple source elements. This implies that subfamily-based methods give an incomplete picture of TE relationships. Studies on selection, functional exaptation, and predictions of horizontal transfer may all be affected. Here, we develop a Bayesian method for inferring TE ancestry that gives the probability that each sequence was replicative, its frequency of replication, and the probability that each extant TE sequence came from each possible ancestral sequence. Applying our method to 986 members of the newly-discovered LAVA family of TEs, we show that there were far more source elements in the history of LAVA expansion than subfamilies identified using the CoSeg subfamily-classification program. We also identify multiple replicative elements in the AluSc subfamily in humans. Our results strongly indicate that a reassessment of subfamily structures is necessary to obtain accurate estimates of mutation processes, phylogenetic relationships and historical times of activity.
Author Summary The most common entities in vertebrate genomes are transposable elements (TEs), DNA sequences that have been repeatedly copied and inserted into new locations throughout the genome. Some TEs have been replicated hundreds of thousands of times, and their ecology and evolutionary history within a genome is thus critical to understanding how genome structure evolves. It was once thought that only a few “master gene” copies could replicate, while the rest were inactive (dead on arrival), but recent computational and laboratory studies have indicated that this is not the case. However, previous methods for reconstructing TE evolutionary history were not designed to solve the problem of determining the ancestral source sequence for large numbers of elements. Here, we present a new method that is. Our method surveys all likely TE ancestors and determines the probability that each modern element arose from each of its plausible ancestors. We applied our method to the gibbon-derived LAVA TE family and to the human AluSc subfamily and inferred many more source elements than indicated by previous methods. This new method will help us better understand TE evolution, including both the impact of sequence on replication and the substitution process after replication.