Question

Define the term Conserved Non-coding Element and explain how CNEs can be identified? (Min 2 and a half pages).

Answer 1

Comparative genomics has revealed a class of non-protein-coding genomic sequences that display an extraordinary degree of conservation between two or more organisms, regularly exceeding that found within protein-coding exons. These elements, collectively referred to as conserved non-coding elements (CNEs), are non-randomly distributed across chromosomes and tend to cluster in the vicinity of genes with regulatory roles in multicellular development and differentiation.

A conserved non-coding Element (CNE) is a DNA sequence of noncoding DNA that is evolutionarily conserved. These sequences are of interest for their potential to regulate gene production. CNEs are organized into functional ensembles called genomic regulatory blocks–dense clusters of elements that collectively coordinate the expression of shared target genes, and whose span in many cases coincides with topologically associated domains. CNEs display sequence properties that set them apart from other sequences under constraint, and have recently been proposed as useful markers for the reconstruction of the evolutionary history of organisms. Disruption of several of these elements is known to contribute to diseases linked with development, and cancer.

All CNEs are likely to perform some function in order to have constraints on their evolution, but they can be distinguished based on where in the genome they are found and how they got there.

• Introns are stretches of sequence found mostly in eukaryotic organisms which interrupt the coding regions of genes, with basepair lengths varying across three orders of magnitude. Intron sequences may be conserved, often because they contain expression regulating elements that put functional constraints on their evolution.
• Some of the most highly conserved noncoding regions are found in the untranslated regions (UTRs) at the 3' end of mature RNA transcripts, rather than in the introns. This suggests an important function operating at the post-transcriptional level. If these regions perform an important regulatory function, the increase in 3'-UTR length over evolutionary time suggests that conserved UTRs contribute to organism complexity.

• Transposable elements- Repetitive elements can accumulate in an organism's genome as the result of a few different transposition processes.

• Pseudogenes are vestiges of once-functional genes disabled by sequence deletions, insertions, or mutations. The primary evidence for this process is the presence of fully functioning orthologues to these inactivated sequences in other related genomes. Pseudogenes commonly emerge following a gene duplication or polyploidization event.

CNEs can only be identified through bioinformatics. The following are the online softwares or tools to identify CNEs.