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One can also compare different engines of evolution in bioinformatic analyses, e.g.

gene duplication for new enzyme activities that are simply tried out, with other methods of

recruiting new enzymes to a metabolic pathway (Schmidt et al. 2003).

So we have learned some nice examples of processes that drive and shape evolution,

first in domains, then in metabolic pathways. There is really a lot of research on engines of

evolution, and the two examples only illustrate this.

Apparently, evolution via metabolites and adaptable protein structures (so-called

changer folds that can bind and process many substrates in related enzyme structures) is

rapid and efficient. On the other hand, this evolution has a necessarily limited starting

material: simple molecules that serve as metabolites and 20 amino acids. Can this starting

material constrain evolution? Interestingly, Stephen J. Gould, among others, has been able

to show how building blocks determine and constrain evolution (Gould 1997). Certainly,

an exciting new possibility is that the chemist, or humans in general, can use their intelli­

gence and also try evolution on a completely new chemistry. Here a very well-known

example is the SELEX process, i.e. the breeding of new RNA molecules by enrichment

and subsequent propagation via the polymerase chain reaction. Jeff Szostak was awarded

the Nobel Prize in 2009 for such experiments on telomerase (protection of the chromo­

some ends). In addition, however, he was able to show that RNA molecules can be grown

for any basic function that a protein enzyme also performs (Adamala et al. 2015). However,

such RNA experiments demonstrate the adaptability of RNA and are important evidence

for an early phase of evolution in which both information storage and enzymatic catalysis

were particularly carried by RNA. Here bioinformatics is enabling exciting new design

experiments with ever new building blocks, for example unprecedented protein folding

types (Garcia et al. 2016; Huang et al. 2016; Bhardwaj et al. 2016 are three recent papers

from David Baker’s internationally leading group), new amino acids (Wang et al. 2016),

artificial new ribosomes (Neumann et al. 2010) or new nucleic acids (Chen et al. 2016).

We can throw off the shackles of our building blocks!

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10.1

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10.5  Protein Evolution: Recognizing Domains