G Protein-Coupled Time Travel: Evolutionary Aspects of GPCR Research

Table 1.

^aCharacterization of naturally occurring missense mutations in human MC4R

^bDegree that given amino acid position is conserved.	^cNumber of amino acid substitutions that retain wild-type functionality.	^cNumber of amino acid substitutions that change wild- type functionality.
^a More than seventy missense mutations (among sixty positions) have been identified in the human MC4R.
^b Stringency of conservation at the given position is determined by sequence comparison of over seventy vertebrate MC4R orthologs: Stringently concerved, no variation; loosely conserved, either of two amino acids occurs among orthologs; not conserved, more than two amino acids can occur at given position among orthologs.
^c About ninety percent of all mutations have been functionally tested. The complete list of missense mutations included in the analysis and the references can be provided on request.
Not conserved	18	3
Loosely conserved	8	9
Stringently conserved	5	24