Conserved sequence

Conserved sequence

A sequence alignment, produced by ClustalO, of mammalian histone proteins.
Sequences are the amino acids for residues 120-180 of the proteins. Residues that are conserved across all sequences are highlighted in grey. Below the protein sequences is a key denoting conserved sequence (*), conservative mutations (:), semi-conservative mutations (.), and non-conservative mutations ( ).[1]

In paralogous sequences). In the case of cross species conservation, this indicates that a particular sequence may have been maintained by evolution despite speciation. The further back up the phylogenetic tree a particular conserved sequence may occur the more highly conserved it is said to be. Since sequence information is normally transmitted from parents to progeny by genes, a conserved sequence implies that there is a conserved gene.

It is widely believed that mutation in a "highly conserved" region leads to a non-viable life form, or a form that is eliminated through natural selection.

Contents

  • Nucleic acid and protein sequences 1
    • Notation 1.1
  • Biological role 2
  • Polymeric carbohydrate sequences 3
  • See also 4
  • References 5
  • Further reading 6

Nucleic acid and protein sequences

Highly conserved DNA sequences are thought to have functional value. The role for many of these highly conserved non-coding DNA sequences is not understood. Ultra-conserved elements or sequences (UCEs or UCRs, ultra-conserved regions) that share 100% identity among human, mouse and rat were first described by Bejerano and colleagues in 2004.[2] One recent study that eliminated four highly conserved non-coding DNA sequences in mice yielded viable mice with no significant phenotypic differences; the authors described their findings as "unexpected".[3] Many regions of the DNA, including highly conserved DNA sequences, consist of repeated sequence (DNA) elements. One possible explanation of the null hypothesis above is that removal of only one or a subset of a repeated sequence could theoretically preserve phenotypic functioning on the assumption that one such sequence is sufficient and the repetitions are superfluous to essential life processes; it was not specified in the paper whether the eliminated sequences were repeated sequences. Although most of the conserved sequences' biological function is still unknown, few conserved sequences derived transcripts showed that their expression is deregulated in human cancer tissues.[4]

Residues conserved among various G protein coupled receptors are highlighted in green.

Notation

A common notation to denote the level of sequence conservation is used by the clustal alignment programs. Below a set of aligned sequences, residue columns are indicated as fully conserved (*), containing only conservative mutations (:), semi-conservative mutations (.), and non-conservative mutations ( ).[5]

Biological role

Highly conserved sequences are often required for basic cellular function, stability or reproduction. Sequence similarity is used as evidence of structural and functional conservation, and evolutionary relationships between sequences. Consequently, functional elements are frequently identified by searching for conserved sequence in a genome.

Conservation of protein-coding sequences leads to the presence of identical amino acid residues at analogous regions of the protein structure and hence similar function. Conservative mutations alter amino acids to similar chemically residues and so may still not affect the protein's function. Among the most highly conserved sequences are the active sites of enzymes and the binding sites of protein receptors.

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F,  

Further reading

  1. ^ "Clustal FAQ #Symbols". Clustal. Retrieved 8 December 2014. 
  2. ^ Bejerano, G; Pheasant, M; Makunin, I; Stephen, S; Kent, WJ; Mattick, JS; Haussler, D (2004-05-28). "Ultraconserved elements in the human genome.". Science 304 (5675): 1321–5.  
  3. ^ Ahituv N, Zhu Y, Visel A; et al. (2007). "Deletion of ultraconserved elements yields viable mice". PLoS Biol. 5 (9): e234.  
  4. ^ Calin, GA; Liu, CG; Ferracin, M; Hyslop, T; Spizzo, R; Sevignani, C; Fabbri, M; Cimmino, A; Lee, EJ; Wojcik, SE; Shimizu, M; Tili, E; Rossi, S; Taccioli, C; Pichiorri, F; Liu, X; Zupo, S; Herlea, V; Gramantieri, L; Lanza, G; Alder, H; Rassenti, L; Volinia, S; Schmittgen, TD; Kipps, TJ; Negrini, M; Croce, CM (September 2007). "Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.". Cancer Cell 12 (3): 215–29.  
  5. ^ "Clustal FAQ #Symbols". Clustal. Retrieved 8 December 2014. 
  6. ^ McLean, Cory Y.; et al. (10 March 2011). "Human-specific loss of regulatory DNA and the evolution of human-specific traits". Nature 471 (7337): 216–219.  
  7. ^ Gross, Liza (September 2007). "Are "Ultraconserved" Genetic Elements Really Indispensable?". PLOS Biology 5 (9): e253.  

References

See also

The monosaccharide sequence of the glycosaminoglycan heparin is conserved across a wide range of species.

Polymeric carbohydrate sequences

. eukaryotes found in most DNA sequence promoter sequence is an example of a highly conserved TATA The [7][6]