Introduction to Evolutionary Conservation

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The positions of <font color='#c000a8'>'''conserved Arg133'''</font> and <font color='00a0a0'>'''variable Glu143'''</font> are highlighted with <span style="background:black; color:yellow;">'''&nbsp;yellow&nbsp;'''</span> halos. You can see that <font color='#c000a8'>'''conserved Arg133'''</font> is in intimate contact with the <font color='#d46a42'>'''DNA'''</font>, while <font color='00a0a0'>'''variable Glu143'''</font> is on the surface, and remote from the contact with the <font color='#d46a42'>'''DNA'''</font>.
The positions of <font color='#c000a8'>'''conserved Arg133'''</font> and <font color='00a0a0'>'''variable Glu143'''</font> are highlighted with <span style="background:black; color:yellow;">'''&nbsp;yellow&nbsp;'''</span> halos. You can see that <font color='#c000a8'>'''conserved Arg133'''</font> is in intimate contact with the <font color='#d46a42'>'''DNA'''</font>, while <font color='00a0a0'>'''variable Glu143'''</font> is on the surface, and remote from the contact with the <font color='#d46a42'>'''DNA'''</font>.
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Revision as of 23:22, 30 September 2012

Mutations occur spontaneously in each generation, randomly changing the amino acid sequences of proteins. Individuals with mutations that impair critical functions of proteins may have resulting problems that make them less able to reproduce. Harmful mutations are lost from the gene pool because the individuals carrying them reproduce less effectively. Over time, only harmless (or very rare beneficial) mutations are maintained in the gene pool. This is evolution.

Examples

Consider the protein methyl CpG binding protein 2 (MeCP2; UniProt MECP2_HUMAN). Although its function is still unclear, it is expressed throughout the body, and disruption of its function causes problems with brain development and function[1]. Some mutations in MeCP2 cause Rett Syndrome, a severely debilitating condition affecting mostly women.


Effect of mutation on protein function

Genetic consequence

Example

Function LOST**

CONSERVED:
mutation LOST from gene pool

R133C*

None

NOT conserved:
mutation remains in gene pool

E143?*

 * in methyl CpG binding protein 2 (MeCP2), 3c2i. Amino acid sequence in 1 letter code:

   ASASPKQRRS IIRDRGPMYD DPTLPEGWTR KLKQRKSGRS AGKYDVYLIN
   PQGKAFRSKV ELIMYFEKVG DTSLDPNDFD FTVTGRGSPS RHHHHHH
         ^          ^
 ** Mutation R133C causes Rett syndrome, a severe neurological disorder.
E143 is highly variable, so mutations here are harmless and remain in the gene pool.
Gray: disordered in crystal, absent in model 3c2i.

Locations of Mutations

MeCp2 protein bound to DNA (crystal structure 3cpi).

Drag the structure with the mouse to rotate

The positions of conserved Arg133 and variable Glu143 are highlighted with  yellow  halos. You can see that conserved Arg133 is in intimate contact with the DNA, while variable Glu143 is on the surface, and remote from the contact with the DNA.

Image:ColorKey ConSurf NoYellow NoGray.gif

Notes and References

  1. ↑ MECP2 article in the National Library of Medicine's Genetic Home Reference

Proteopedia Page Contributors and Editors (what is this?)

Eric Martz, Alexander Berchansky, Verónica Gómez Gil

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