The structural basis of molecular adaptation

G. Brian Golding, Antony M. Dean

Research output: Contribution to journalReview articlepeer-review

210 Scopus citations


The study of molecular adaptation has long been fraught with difficulties, not the least of which is identifying out of hundreds of amino acid replacements those few directly responsible for major adaptations. Six studies are used to illustrate how phylogenies, site-directed mutagenesis, and a knowledge of protein structure combine to provide much deeper insights into the adaptive process than has hitherto been possible. Ancient genes can be reconstructed, and the phenotypes can be compared to modern proteins. Out of hundreds of amino acid replacements accumulated over billions of years those few responsible for discriminating between alternative substrates are identified. An amino acid replacement of modest effect at the molecular level causes a dramatic expansion in an ecological niche. These and other topics are creating the emerging field of 'paleomolecular biochemistry'.

Original languageEnglish (US)
Pages (from-to)355-369
Number of pages15
JournalMolecular biology and evolution
Issue number4
StatePublished - Apr 1998


  • Amino acid replacements
  • Molecular adaptation
  • Phylogeny
  • Protein structure


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