Summary:
The study of fusion and fission events is of a great importance for the
investigation of the evolutionary patterns of proteins and organisms, but also
for the prediction of protein-protein interactions. In this project the
fusion/fission events were used to study the protein evolution in 104 well
known human bacterial pathogens. Bacterial pathogens evolve in an unusual
manner (reductive evolution), because of their interaction with the host. These
bacteria are under pressure in order to survive in the environment of the
interior of the host, which is a quite new and unfriendly environment. Such an
environment leads to the evolution of a rather plastic genome that allows a
great number of recombinations. The greater frequency of recombination along
with the high evolutionary pressure, seem to influence the rate of fusion and
fission events, causing an increase of multiple fusion on fission events (22%),
that until today thought to be an exception to the rule of the evolutionary
uniqueness of these events. Human bacterial pathogens also display a high
predominance of fission events (86%), over fusion events. This predominance, is
observed for the first time, while all previous studies with different groups
of organisms, had shown that fusion events always prevail over fission events.
These findings are considered to be caused from the events that took place
during the late evolution of the human bacterial pathogens, where their
percentages were even higher (44% multiple events, 94% fission events). In
contrast to the late evolution of these bacteria, early evolution is
characterized by a great preponderance of fusion over fission events (81% over
13%). These differences between these two evolutionary timescales, reveal that
in early evolution the structural complicated proteins were positively
selected, by natural selection, probably because of their specific function and
their role in the development of the metabolism. During the late evolution, the
selection turned towards less complicated protein structures, which are
characterized by their multiple, flexible, and less specific functions.
These smaller proteins are especially useful for the adjustment of an organism
in a new environment, because they can cover the need for new functions. The
human bacterial pathogens are under pressure to adapt in a, comparative with
other mammals, new host, who has developed highly sophisticated defense
mechanisms (immune system, antibacterial drug use). Human bacterial pathogen’s
fitness to the hosts environment, totally depends on the production of new and
more functionally flexible proteins, because the bacterial diversity and their
ability to exchange DNA, is significantly reduced by the hosts restriction.
This is why smaller proteins are 9
positively selected during the late evolution, the same proteins that were a
product of fission and not fusion events.
Evolution study can be used for the development of new applications. This study
suggests a new method for the prediction of possible protein-protein
interactions by adding an extra evolutionary filter to the preexisting Rosetta
Stone Analysis. The new method is called Champollion Profiling and it improves
the prediction of protein-protein interactions in comparison with the Rosetta
Stone Analysis (25% over 9% probability that the results correspond to true
interactions).
Keywords:
Fusion, Fission, Evolution, Pathogens, Interaction
