Intron exon boundary junctions in human genome have in-built unique structural and energetic signals

Abstract

Precise identification of correct exon–intron boundaries is a prerequisite to analyze the location and structure of genes. The existing framework for genomic signals, delineating exon and introns in a genomic segment, seems insufficient, predominantly due to poor sequence consensus as well as limitations of training on available experimental data sets. We present here a novel concept for characterizing exon–intron boundaries in genomic segments on the basis of structural and energetic properties. We analyzed boundary junctions on both sides of all the exons (3 28 368) of protein coding genes from human genome (GENCODE database) using 28 structural and three energy parameters. Study of sequence conservation at these sites shows very poor consensus. It is observed that DNA adopts a unique structural and energy state at the boundary junctions. Also, signals are somewhat different for housekeeping and tissue specific genes. Clustering of 31 parameters into four derived vectors gives some additional insights into the physical mechanisms involved in this biological process. Sites of structural and energy signals correlate well to the positions playing important roles in pre-mRNA splicing.

Molecular dynamics simulation-based trinucleotide and tetranucleotide level structural and energy characterization of the functional units of genomic DNA

“…7 Like promoter identification, detecting accurate intron-exon architecture within a gene is essential and has recently received significant attention in eukaryotic genome annotation. 17 The primary focus of categorization was on the splice sites (SSs) and junction sequences. Conventionally, it includes a G-T nucleotide pair at the 5 0 end of the intron, and an A-G nucleotide pair at the 3 0 end.…”

“…Conventionally, it includes a G-T nucleotide pair at the 5 0 end of the intron, and an A-G nucleotide pair at the 3 0 end. 7,17 With the continuous characterization of SSs, many sequence alterations occur at these sites. Further, the identification of the exon-intron junctions becomes challenging due to the presence of alternative splicing.…”

“…Since there exists no universal model for the identification and characterization of these genomic elements, it is necessary to come up with a chemistry-based approach to annotation. In our previous research communications, 6,17,[30][31][32][33][34] we have elucidated the importance of the structural and energy-based profiling of the DNA elements. Likewise, other groups have also focused on capturing the structural and energy signals of various regions by considering properties like free energy, A-philicity, curvature, bendability, inter-BP properties, and DNA duplex stability under stress.…”

“…Compared to our previous research, 6,17 which utilizes the X-ray-based dinucleotide data of B-DNAs to profile the TSSs in prokaryotes and exon-intron boundaries in humans, in this present work, we have taken into consideration the neighbouring effects by mapping structural and energetic parameters of all the unique tri and tetra-nucleotide steps. 6 The biophysical features utilized in this research have been computed through micro-second-long molecular dynamics (MD) simulations on all the possible tri-and tetranucleotide steps.…”

Analysis of nucleoid‐associated protein‐binding regions reveals DNA structural features influencing genome organization in Mycobacterium tuberculosis

“…Global structural properties such as DNA bending (intrinsic curvature and ligand‐induced bending or flexibility), DNA duplex stability, supercoil‐induced DNA destabilization and topology have been characterized at more than one helical turn of DNA [49]. Several experimental and high‐throughput computational studies revealed that unique stability, flexibility and curvature of DNA sequences play key roles in physiological processes like the orchestration of transcription and replication machinery [53–59]. Of note, the DNA compaction which results in proximal rearrangement of long stretches of DNA might be dependent on anisotropic DNA structures by lowering the free energy of the transitions.…”