Sequence Conservation is important for 2 reasons:

1. EVOLUTIONARY.   It makes sense that if closely related species are compared, their proteins will be very similar .... in other words at most positions in the peptide chain, the amino acids will be identical. This is called conservation. Conversely, if the proteins from distantly related species are compared, it would be expected that the proteins would be dissimilar ... in other words the amino acid sequence would not be conserved. This elementary logic implies that evolutionary divergence can be tracked by analysis of protein similarities. The next section will show how evolutionary "distance" is a direct correlate of conservation in the amino acid sequence of proteins.

 
2. FUNCTIONAL.  If an amino acid at a particular position plays a vital role in the function of the protein, then any change in the amino acid would be expected to decrease the function or even destroy it altogether. Thus any individual which experienced a mutation to the gene, which changed the amino acid sequence at this position, would probably exhibit an inferior phenotype. Thus, such a mutation would be selected against through evolutionary time.

On the other hand, an amino acid which was not important to the function of the protein might be changed with little effect on function. Consequently an individual with a mutation which changes an unimportant amino acid will not be selected against.

Click on thumbnail to see full-size!	The thumbnail shows an alignment of b-globin from humans and 10 other mammals. Among the positions at which amino acids are most strongly conserved are: Glutamic Acid (E) at position 6. Hisitidne (H) at position 63. Histidine (H) at position 93. amino acids 62-68 amino acids 88-103 and 106-108 It might be hypothesized that these amino acids are important to function because they have been conserved (changing them would impair function, and would be selected against).
Click on thumbnail to see full-size!	The conserved positions have been mapped onto a graphic showing the secondary and tertiary structure of human beta globin.  Recall that a critical component of a-globin, b-globin and myoglobin is the porphyrin ring .... which binds iron ..... which binds oxygen.  Now it makes sense that the amino acids identified above were conserved! Hisitidne (H) at position 63. pins the Fe atom in place within the porphyrin ring from one side. Histidine (H) at position 92. pins the Fe atom in place from one side. amino acids 62-68 forms one side of the binding pocket into which the porphyrin ring is bound. amino acids 88-103 and 106-108 forms another side, and the bottom, of the binding pocket. Glutamic Acid (E) at position 6. An anomaly! In sickle beta globin, this hydrophilic amino acid is changed to hydrophobic valine. This causes the hemoglobins to polymerize into long, stiff rods which distort the erythrocytes into a sickled shape.
Of course, the mere fact that something makes sense, does not make it true! Hypotheses such as this must still be confirmed by solving the structure using X-ray crystallography. However hundreds of protein structures have been solved, and they all show the absolute dependence of protein function on molecular structure!
Click on thumbnail to see full-size!	It is argued that conserved amino acids have been conserved because changing them impairs the function of the protein, so that the phenotype is selected against. It therefore follows that an individual who carries such a mutation should have an abnormal phenotype which makes them less healthy .... in other words a genetic disease! The classic example is sickle cell anemia. However, as shown in the graphic to the left, there are many variants of beta globin which have been discovered in people from all over the world. It would be predicted that these people would not be completely healthy. The actual clinical symptoms are described in OMIM.