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Monday, June 25, 2012

The Real Barrier to Unguided Human Evolution


Vitruvian Man.jpgComparing DNA sequences and estimating by how many nucleotides we differ from chimps doesn't tell us much about what makes us human. Many of those nucleotide differences have no effect, because they are the product of neutral mutation and genetic drift. While these neutral mutations may affect the over-all mutation count, they don't answer how many mutations are required for the transition from chimp-like to human.
This problem is analogous to one we examined concerning protein evolution last year in the journal BIO-Complexity (Gauger and Axe 2011). Converting one protein to another's function can be viewed as a version, in miniature, of converting one species to another. But it is much easier to convert proteins than species.
We began by identifying two proteins that are close together in structure, but that have distinct functions. We examined what the minimal number of mutations to convert one protein to the other were. If all the places where they differed had to be changed, that would mean we would have to switch 70% of one protein to achieve conversion to the other's function. It's unlikely that all those mutations are required, however, since many if not most of those changes are due to neutral mutation and drift, just like in the chimp-like to human case.
So to estimate the minimal number of mutations required for conversion to a new function, we identified and tested the most likely amino acid candidates using structural and sequence comparisons, one by one and in combination. We ended up changing nearly the entire active site to look like the target protein, but failed to achieve conversion.
Based on the number of groups we changed, we made a minimum estimate that seven specific mutations would be required for a functional shift to be observed. To get seven coordinated mutations takes far too long, even for bacteria, with their high mutation rate and large population sizes. 10^27 years is our estimate, based on Doug Axe's population genetics model, also published in BIO-Complexity.
Personally, I think the chimp-like to human conversion would have to have taken many more years than any protein conversion, 
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