Dataset Information

Molecular reconstruction of extinct LINE-1 elements and their interaction with nonautonomous elements.

ABSTRACT: Non-long terminal repeat retroelements continue to impact the human genome through cis-activity of long interspersed element-1 (LINE-1 or L1) and trans-mobilization of Alu. Current activity is dominated by modern subfamilies of these elements, leaving behind an evolutionary graveyard of extinct Alu and L1 subfamilies. Because Alu is a nonautonomous element that relies on L1 to retrotranspose, there is the possibility that competition between these elements has driven selection and antagonistic coevolution between Alu and L1. Through analysis of synonymous versus nonsynonymous codon evolution across L1 subfamilies, we find that the C-terminal ORF2 cys domain experienced a dramatic increase in amino acid substitution rate in the transition from L1PA5 to L1PA4 subfamilies. This observation coincides with the previously reported rapid evolution of ORF1 during the same transition period. Ancestral Alu sequences have been previously reconstructed, as their short size and ubiquity have made it relatively easy to retrieve consensus sequences from the human genome. In contrast, creating constructs of extinct L1 copies is a more laborious task. Here, we report our efforts to recreate and evaluate the retrotransposition capabilities of two ancestral L1 elements, L1PA4 and L1PA8 that were active ~18 and ~40 Ma, respectively. Relative to the modern L1PA1 subfamily, we find that both elements are similarly active in a cell culture retrotransposition assay in HeLa, and both are able to efficiently trans-mobilize Alu elements from several subfamilies. Although we observe some variation in Alu subfamily retrotransposition efficiency, any coevolution that may have occurred between LINEs and SINEs is not evident from these data. Population dynamics and stochastic variation in the number of active source elements likely play an important role in individual LINE or SINE subfamily amplification. If coevolution also contributes to changing retrotransposition rates and the progression of subfamilies, cell factors are likely to play an important mediating role in changing LINE-SINE interactions over evolutionary time.

SUBMITTER: Wagstaff BJ

PROVIDER: S-EPMC3525338 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Molecular reconstruction of extinct LINE-1 elements and their interaction with nonautonomous elements.

Wagstaff Bradley J BJ Kroutter Emily N EN Derbes Rebecca S RS Belancio Victoria P VP Roy-Engel Astrid M AM

Molecular biology and evolution 20120823 1

Non-long terminal repeat retroelements continue to impact the human genome through cis-activity of long interspersed element-1 (LINE-1 or L1) and trans-mobilization of Alu. Current activity is dominated by modern subfamilies of these elements, leaving behind an evolutionary graveyard of extinct Alu and L1 subfamilies. Because Alu is a nonautonomous element that relies on L1 to retrotranspose, there is the possibility that competition between these elements has driven selection and antagonistic c ...[more]

PMID: 22918960

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Project description:BackgroundMosquitoes are important pathogen vectors affecting human and other animals. Studies on genetic control of mosquito mediated disease transmission gained traction recently due to mosquito transgenesis technology. Active transposons are considered valuable tools to propagate pathogen resistance transgenes among mosquitoes, rendering the whole population recalcitrant to diseases. A major hurdle in this approach is the inefficient remobilization activity after the integration of heterologous transposon vectors bearing transgenes into chromosomes. Therefore, endogenous active transposons in mosquito genomes are highly desirable.ResultsStarting with the transposable element database of the yellow fever mosquito Aedes aegypti genome, detailed analyses of the members of each TE family were performed to identify sequences with multiple identical copies, an indicator of their latest or current transposition activity. Among a dozen of potentially active TE families, two DNA elements (TF000728 and TF000742 in TEfam) are short and nonautonomous. Close inspection of the elements revealed that these two families were previously mis-categorized and, unlike other known TEs, insert specifically at dinucleotide "AT". These two families were therefore designated as ATon-I and ATon-II. ATon-I has a total copy number of 294, among which three elements have more than 10 identical copies (146, 61 and 17). ATon-II has a total copy number of 317, among which three elements have more than 10 identical copies (84, 15 and 12). Genome wide searches revealed additional 24 ATon families in A. aegypti genome with nearly 6500 copies in total. Transposon display analysis of ATon-1 family using different A. aegypti strains suggests that the elements are similarly abundant in the tested mosquito strains.ConclusionATons are novel mobile genetic elements bearing terminal inverted repeats and insert specifically at dinucleotide "AT". Five ATon families contain elements existing at more than 10 identical copies, suggesting very recent or current transposition activity. A total of 24 new TE families with nearly 6000 copies were identified in this study.

Project description:Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is approximately 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in approximately 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our reconstruction is able to serve as a valuable resource in additional analyses involving objects from multiple molecular -omes. For that purpose, RefRec is freely available in the Systems Biology Markup Language format.

Dataset Information

Molecular reconstruction of extinct LINE-1 elements and their interaction with nonautonomous elements.

Publications

Molecular reconstruction of extinct LINE-1 elements and their interaction with nonautonomous elements.

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