Holliday Junctions Are Associated with Transposable Element Sequences in the Human Genome

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Holliday junctions (HJs) are key intermediates in DNA recombination and repair.
• HJs originate from a degenerate 10-nucleotide sequence with a 3-nucleotide core motif.

Purpose of the Study:

• To investigate the association between the human HJ degenerate sequence and transposable elements (TEs).
• To identify specific TE families (ALU, LINE, SVA, HERV) interacting with HJs.
• To determine the genomic distribution and proximity of TE-associated HJs to human genes.

Main Methods:

• Bioinformatic analysis of the human genome to identify HJ sequences and their co-occurrence with TEs.
• Identification of six distinct HJ sequence motifs.
• Genomic localization of sequences containing both HJs and TEs.
• Phylogenetic analysis to assess HJ presence in active and inactive TEs.

Main Results:

• 1319 out of 2982 identified HJs were associated with TEs, with a median distribution of 1 per 2.4 Mb.
• HJs with higher GC content were more prevalent.
• Significant association of HJs with DNA elements (41.94%) and retroelements, including ALUs (72.72%), LINEs (42.94%), and HERVs (84.5%).
• TE-associated HJs were predominantly located within 1 Mb of human genes.

Conclusions:

• This is the first report linking human HJs with mobile elements (TEs).
• Specific HJ forms exhibit a preference for active retrotransposon families like ALUs and LINEs.
• Retrotransposon-incorporated HJs may contribute to genome plasticity, recombination, and DNA repair through retrotransposition.