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Birth of three stowaway-like MITE families via microhomology-mediated miniaturization of a Tc1/Mariner element in the yellow fever mosquito.

Yang G, Fattash I, Lee CN, Liu K, Cavinder B - Genome Biol Evol (2013)

Bottom Line: Upon close inspection of the sequence junctions, the internal deletions during the formation of these three MITE families always occurred between two microhomologous sites (6-8 bp).These results suggest that multiple MITE families may originate from a single ancestral autonomous element, and formation of MITEs can be mediated by sequence microhomology.Ozma and its related MITEs are exceptional candidates for the long sought-after endogenous active transposon tool in genetic control of mosquitoes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Toronto Mississauga, Ontario, Canada.

ABSTRACT
Eukaryotic genomes contain numerous DNA transposons that move by a cut-and-paste mechanism. The majority of these elements are self-insufficient and dependent on their autonomous relatives to transpose. Miniature inverted repeat transposable elements (MITEs) are often the most numerous nonautonomous DNA elements in a higher eukaryotic genome. Little is known about the origin of these MITE families as few of them are accompanied by their direct ancestral elements in a genome. Analyses of MITEs in the yellow fever mosquito identified its youngest MITE family, designated as Gnome, that contains at least 116 identical copies. Genome-wide search for direct ancestral autonomous elements of Gnome revealed an elusive single copy Tc1/Mariner-like element, named as Ozma, that encodes a transposase with a DD37E triad motif. Strikingly, Ozma also gave rise to two additional MITE families, designated as Elf and Goblin. These three MITE families were derived at different times during evolution and bear internal sequences originated from different regions of Ozma. Upon close inspection of the sequence junctions, the internal deletions during the formation of these three MITE families always occurred between two microhomologous sites (6-8 bp). These results suggest that multiple MITE families may originate from a single ancestral autonomous element, and formation of MITEs can be mediated by sequence microhomology. Ozma and its related MITEs are exceptional candidates for the long sought-after endogenous active transposon tool in genetic control of mosquitoes.

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Microhomology between break point sequences. Green sequences, left break points; red sequences, right break points; black base letters, aberrant nucleotides introduced; vertical black lines in sequences, junctions; number of bases, length between the two break points; underlined letters, microhomologous sequences.
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evt146-F6: Microhomology between break point sequences. Green sequences, left break points; red sequences, right break points; black base letters, aberrant nucleotides introduced; vertical black lines in sequences, junctions; number of bases, length between the two break points; underlined letters, microhomologous sequences.

Mentions: Little is known about mechanisms of origination of MITE families from autonomous elements. The internal deletions of an autonomous element in MITE formation fall in the category of chromosome microdeletion. Different mechanisms responsible for these deletion events may leave their characteristic sequence features at or around break points. To understand what mechanisms may be involved in the generation of these MITE sequences, break point sequences at the junctions were inspected. The break point for Gnome on the left is immediately after the left TIR whereas the break point on the right is 52 bp upstream of the stop codon of the transposase coding sequence. The 8 bp sequence (CGGACACT) after the left break point is very similar to that before the right break point (CGGAACCT) with a mismatch of “CA/AC.” In addition, an information scar of a “T” to “G” transversion is present at the junction of the break points (fig. 6A) (Verdin et al. 2013). The left break point of Elf is 280 bp into the transposase coding sequence and the right break point is 28 bp upstream of the stop codon. Similarly, the 6 bp (GGAAGT) right after the left break point is very similar to that after the right break point (GAAAGT) with a “G/A” mismatch (fig. 6B). Despite the unusual configuration of Goblin as described earlier, break points show a 6 bp (AACTTT) microhomology (fig. 6C). An information scar of a single nucleotide “T” insertion is present at the junction. Though microhomologies of this size range can occur with replication-based mechanisms, mismatches in the microhomologous sites and, particularly, the insertional information scars are hallmark features of MMEJ. Therefore, gap repair of the double-stranded DNA breaks resulted from the excision of Ozma followed by MMEJ repairing was likely to be involved in the generation of Gnome, Elf, and Goblin. The formation of Goblin may also involve template switching during the new strand synthesis as shown in the proposed model (fig. 7). In addition, the miniature element derived from Gnome internal deletion shows microhomology of three nucleotides, suggesting a classical nonhomologous end joining (NHEJ) process (fig. 6D).Fig. 6.—


Birth of three stowaway-like MITE families via microhomology-mediated miniaturization of a Tc1/Mariner element in the yellow fever mosquito.

Yang G, Fattash I, Lee CN, Liu K, Cavinder B - Genome Biol Evol (2013)

Microhomology between break point sequences. Green sequences, left break points; red sequences, right break points; black base letters, aberrant nucleotides introduced; vertical black lines in sequences, junctions; number of bases, length between the two break points; underlined letters, microhomologous sequences.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814204&req=5

evt146-F6: Microhomology between break point sequences. Green sequences, left break points; red sequences, right break points; black base letters, aberrant nucleotides introduced; vertical black lines in sequences, junctions; number of bases, length between the two break points; underlined letters, microhomologous sequences.
Mentions: Little is known about mechanisms of origination of MITE families from autonomous elements. The internal deletions of an autonomous element in MITE formation fall in the category of chromosome microdeletion. Different mechanisms responsible for these deletion events may leave their characteristic sequence features at or around break points. To understand what mechanisms may be involved in the generation of these MITE sequences, break point sequences at the junctions were inspected. The break point for Gnome on the left is immediately after the left TIR whereas the break point on the right is 52 bp upstream of the stop codon of the transposase coding sequence. The 8 bp sequence (CGGACACT) after the left break point is very similar to that before the right break point (CGGAACCT) with a mismatch of “CA/AC.” In addition, an information scar of a “T” to “G” transversion is present at the junction of the break points (fig. 6A) (Verdin et al. 2013). The left break point of Elf is 280 bp into the transposase coding sequence and the right break point is 28 bp upstream of the stop codon. Similarly, the 6 bp (GGAAGT) right after the left break point is very similar to that after the right break point (GAAAGT) with a “G/A” mismatch (fig. 6B). Despite the unusual configuration of Goblin as described earlier, break points show a 6 bp (AACTTT) microhomology (fig. 6C). An information scar of a single nucleotide “T” insertion is present at the junction. Though microhomologies of this size range can occur with replication-based mechanisms, mismatches in the microhomologous sites and, particularly, the insertional information scars are hallmark features of MMEJ. Therefore, gap repair of the double-stranded DNA breaks resulted from the excision of Ozma followed by MMEJ repairing was likely to be involved in the generation of Gnome, Elf, and Goblin. The formation of Goblin may also involve template switching during the new strand synthesis as shown in the proposed model (fig. 7). In addition, the miniature element derived from Gnome internal deletion shows microhomology of three nucleotides, suggesting a classical nonhomologous end joining (NHEJ) process (fig. 6D).Fig. 6.—

Bottom Line: Upon close inspection of the sequence junctions, the internal deletions during the formation of these three MITE families always occurred between two microhomologous sites (6-8 bp).These results suggest that multiple MITE families may originate from a single ancestral autonomous element, and formation of MITEs can be mediated by sequence microhomology.Ozma and its related MITEs are exceptional candidates for the long sought-after endogenous active transposon tool in genetic control of mosquitoes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Toronto Mississauga, Ontario, Canada.

ABSTRACT
Eukaryotic genomes contain numerous DNA transposons that move by a cut-and-paste mechanism. The majority of these elements are self-insufficient and dependent on their autonomous relatives to transpose. Miniature inverted repeat transposable elements (MITEs) are often the most numerous nonautonomous DNA elements in a higher eukaryotic genome. Little is known about the origin of these MITE families as few of them are accompanied by their direct ancestral elements in a genome. Analyses of MITEs in the yellow fever mosquito identified its youngest MITE family, designated as Gnome, that contains at least 116 identical copies. Genome-wide search for direct ancestral autonomous elements of Gnome revealed an elusive single copy Tc1/Mariner-like element, named as Ozma, that encodes a transposase with a DD37E triad motif. Strikingly, Ozma also gave rise to two additional MITE families, designated as Elf and Goblin. These three MITE families were derived at different times during evolution and bear internal sequences originated from different regions of Ozma. Upon close inspection of the sequence junctions, the internal deletions during the formation of these three MITE families always occurred between two microhomologous sites (6-8 bp). These results suggest that multiple MITE families may originate from a single ancestral autonomous element, and formation of MITEs can be mediated by sequence microhomology. Ozma and its related MITEs are exceptional candidates for the long sought-after endogenous active transposon tool in genetic control of mosquitoes.

Show MeSH
Related in: MedlinePlus