Conserved Non-Coding Sequence

Conserved noncoding sequences (CNS) are regions of the genome which do not code for proteins, yet show significantly slower rates of sequence change than truly nonfunctional sequences. Current evidence suggests that many or most conserved noncoding sequences are involved in regulating the expression of neighboring genes.

CNS in plants tend to be much smaller than those found in animals.

An example of some five prime conserved noncoding sequences identified by comparing syntenic orthologs in the genomes of peach and chocolate using the CNS Discovery Pipeline. To regenerate this analysis click here . Another CNS example in the grasses.

Examples of regulatory CNS

Lateral Suppressor

Lateral Suppressor (LAS) is a tightly regulated gene expressed specifically at the adaxial boundary of newly initiating leaf primordia. In 2011 Bodo Raatz and co-workers reported that this very specific expression pattern was regulated by a 3' prime (downstream) enhancer/suppressor which induces expression of reporter genes within the usual expression domain of LAS and represses their expression in other contexts. The authors also showed the the equivalent sequence in tomato (an asterid) retains the same function and that this conserved noncoding sequence is present downstream of orthologs of LAS in both eudicots and grasses (monocots).

Raatz, B. et al. (2011). Specific expression of LATERAL SUPPRESSOR is controlled by an evolutionarily conserved 3′ enhancer. The Plant Journal 68: 400-412.

Identifying CNS

Different groups have developed different criteria for what constitutes a CNS. For our own research we define a CNS as a blast hit at least as significant as a 15 base pair exact match present at a syntenic location relative to pair of homeologous or orthologous genes. For these criteria to work, the two genomes being compared should have a modal synonymous substitution rate of between .5 and .99. In more closely related genomes sequences which are not functionally constrained can still retain significant sequence similarity (carry over), while in genomes with greater divergence, base pair substitutions often render even functional CNS undetectable.

In animals, where conserved noncoding elements tend to be larger and evolve at a (relative to plants) glacial rate, different parameters may apply.

To automate the process of identifying and filtering conserved noncoding sequences, the Freeling lab has developed the CNS Discovery Pipeline.