This document discusses two main theories for how enzyme systems evolved: retrograde evolution and patchwork evolution. Retrograde evolution proposes that pathways evolve backwards, with newer reactions preceding existing ones. Patchwork evolution suggests that enzymes initially had broad specificities and specialized over time through gene duplication. While some evidence supports retrograde evolution, more data favors patchwork evolution. However, the CS2 hydrolase enzyme appears to be an exception, as its structure and function indicate it did not evolve but was purposefully designed. In conclusion, the theories of enzyme evolution are still being refined as exceptions are discovered.

1. biochemaholic.wordpress.com

2. INTRODUCTION :
 Enzymes are proteins that catalyze reactions that are
necessary for life.
 They are composed of strings of amino acids, and the
particular sequence of amino acids determines what three-dimensional
shape each protein has, and what enzymatic
function it carries out.
 Biologists categorize enzymes into families based on similarity
of structure. The more similar the structure, the closer the
evolutionary relationship is presumed to be.

3. BASIC CONCEPT :
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4. HOW DID THEY EVOLVE?
 There are 2 theories proposed to explain the evolution of
enzyme systems:
 Retrograde
 Patchwork

5. RETROGRADE :
 In 1945 one of the first theories regarding the evolution of
metabolic pathways, often referred to as the retrograde
evolution model, was proposed by Horowitz.
 It states that :
 Pathways evolve backwards: the end
product of the newly evolved
reaction is the substrate of the
existing one.

6. E 1
A B
Picture adapted from Betts & Russell, 2009

7. E2 E1
X A B
Picture adapted from Betts & Russell, 2009

8.  Successive reactions in the pathway would therefore be
catalysed by homologous enzymes.
E2 E1
X A B
Picture adapted from Betts & Russell, 2009

9. PATCHWORK
 In 1976 Jensen proposed the recruitment evolution theory,
more often referred to as the patchwork evolution model .The
patchwork evolution model states that
“Enzymes initially have broad substrate
specificities and that specialization takes place
by way of gene duplication”.

14. E1
A
A’

15. A
E3 E1
A’
E2

17. IN FAVOR OF RETROGRADE EVOLUTION MODEL
 Saqi & Sternberg showed that some super-families have a
general tendency to appear twice or more in one particular
pathway(s).
Ex : Deoxyribonucleoside kinases, which catalyse the
phosphorylation of deoxyribonucleosides, are present in
several copies in most multicellular organisms and therefore
represent an excellent model to study retrograde evolution.

18. CONT…….
 Rison et al showed that homologous enzymes are found at close
distances within the (extended) pathways of E. coli .
 Alves et al showed that homologous enzymes are also found close
to each other in the whole metabolic network.
pubs.rsc.org

19. IN FAVOR OF PATCHWORK
 The patchwork evolution model holds that there should
be many pairs of homologous enzymes that catalyze
basically the same kind of reaction, where one or more
substrates are non-identical but similar.
 Support for this theory is more abundant than for the
retrograde evolution model .
 The TIM-barrel containing enzymes have been found in
many different pathways .
 The homologous pairs of small molecule metabolism
enzymes of E. coli have been shown to be evenly
distributed within and across pathways

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22. ͞EŶzyŵes ĐouldŶ’t eǀolǀe͟
*The investigators compared the three-dimensional structures of
similarly shaped enzymes that are found in different species of
bacteria:
 One enzyme splits water and combines the resulting hydrogen
atoms with sulfur . (CS2 hydrolase]
 Another class of enzymes that also splits water molecules, but then
combines the hydrogen with a carbon-based molecule.
*The core structure of the CS2 hydrolase like that of similar enzymes,
is critical. The scientists wrote in Nature, "Any change in this area
of the protein [enzyme] adversely affected protein activity."
*The researchers also found that CS2 hydrolase is distinct from
enzymes with an otherwise identical core because it has an
additional long, narrow tunnel through which only CS2 can pass.
The tunnel "functions as a specificity filter," ensuring that no
similar molecule such as carbon dioxide enters.

23. CoŶt…
• The DNA that codes for the tunnel portion of the CS2hydrolase gene is surrounded
by unique sequences, indicating that this DNA portion may have been added to the
main enzyme's DNA. Perhaps some unknown cellular mechanism "stitched in" this
extra bit at just the right place among the bacteria's 1.8 million DNA bases, adding
the tunnel portion to a CO2-converting enzyme and thereby forming CS2 hydrolase.
Arguments :
• If the gene jumped from another bacterium to this one, it did not
evolve because it already existed elsewhere.
• In addition to the enzymes themselves, another mechanism had to already
exist that could recognize, accept, and insert the foreign DNA in just the
right place. Only then could it retrofit an enzyme in just the right way to
enable the bacterium to live on sulfur.
• This ignores the facts that no new DNA actually "emerged," and the proper
placement of transferred DNA required just the opposite of evolution—
purposeful design.

24. Conclusion from their research :
**CS2 hydrolase did not evolve. In fact, experimental science
shows that this enzyme functions today only because of its
precise and specific arrangement of parts. And like any
machine with multiple, interconnected parts, whether
biological or man-made, all the correct parts assembled in the
correct configuration were needed from the very beginning.

25. ͞The theories of evolution are still under
the process of evolution͟
*The whole concept can be summarized by the fact that the 2 theories of evolution of
enzymes, proposed are not universally accepted; i.e. there are exceptions to the
theories (ex : CS2 hydrolase).
*Scientists are still working on the theories to make them more universally acceptable.
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26. References
Research articles
• ͞Netǁork aŶalysis of ŵetaďoliĐ eŶzyŵe eǀolutioŶ
inEscherichia Đoli” ďy Sara Light and Per Kraulis.
• ͞Neǁ “tudy “hoǁs EŶzyŵes CouldŶ't Eǀolǀe͟ ďy BriaŶ
Thomas, M.S.
Web links :
• http://www.biomedcentral.com
• http://www.evolutionnews.org/