Selective and Structural Constraints


The neutral theory of molecular evolution predicts that the rate of evolution will be low in portions of genes and of proteins that are functionally important. This insight is the basis for bioinformatics strategies that use sequence information to make functional predictions.

Keywords: amino acid sequence evolution; neutral theory; purifying selection; protein function; synonymous and nonsynonymous substitution

Figure 1.

Alignment (Thompson et al., ) of the mature polypeptide sequences of four vertebrate aspartic proteinases. The conserved active site residues are boxed.



Duret L and Mouchiroud D (2000) Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Molecular Biology and Evolution 17: 68–74.

Hughes AL (1999) Adaptive Evolution of Genes and Genomes. New York, NY: Oxford University Press.

Hughes AL, Friedman R and Murray M (2002) Genome‐wide pattern of synonymous nucleotide substitution in two complete genomes of Mycobacterium tuberculosis. Emerging Infectious Diseases 8: 1342–1346.

Hughes AL and Nei M (1988) Pattern of nucleotide substitution at MHC class I loci reveals overdominant selection. Nature 335: 167–170.

Jordan IK, Rogozin IB, Wolf YI and Koonin EV (2002) Microevolutionary genomics of bacteria. Theoretical Population Genetics 61: 435–444.

Kimura M (1977) Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 267: 275–276.

Kimura M (1983) The Neutral Theory of Molecular Evolution. Cambridge, UK: Cambridge University Press.

Li W‐H, Wu C‐I and Luo C‐C (1985) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Molecular Biology and Evolution 2: 150–174.

Sielecki AR, Fedorov AA, Boodhoo A, Andreeva NS and James NG (1990) Molecular and crystal structures of monoclinic porcine pepsin refined at 1.8 Å resolution. Journal of Molecular Biology 214: 143–170.

Thompson JD, Higgins DG and Gibson TJ (1994) CLUSTALW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position‐specific gap penalties and weight matrix choice. Nucleic Acids Research 22: 4673–4680.

Further Reading

Kimura M (1986) DNA and the neutral theory. Philosophical Transactions of the Royal Society of London B312: 343–354.

Li W‐H (1997) Molecular Evolution. Sunderland MA: Sinauer.

Mount DW (2001) Bioinformatics: Sequence and Genome Analysis. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

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How to Cite close
Hughes, Austin L(Jul 2006) Selective and Structural Constraints. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005124]