|Authors: ||Buljan, Marija|
|Supervisors: ||Bateman, Alex|
|Issue Date: ||11-Jan-2011|
|Abstract: ||Proteins are the basic building blocks and functional units in all living organisms.
Moreover, differences between species can frequently be explained with
differences in their protein complements. Importantly, proteins are often
composed of segments, i.e. domains that have a certain level of evolutionary,
structural and/or functional independence. The majority of proteins in nature
contain two or more domains, and an individual domain can often occur in
combinations with different domain partners.
In the first part of my thesis, I traced the history of animal gene families
and the proteins these genes encode. By this means, I was able to infer events
where changes in protein domain architectures took place. This showed that
both insertions and deletions of single copy domains preferentially occur at
protein termini, but also that changes are more likely to occur after gene
duplication than organism speciation. Finally, domains that were most
frequently gained were the ones that are related to an increase in organismal
complexity, thus underlining the important role of domain shuffling in animal
In the second part of my thesis, I focused on a set of high confidence
domain gain events and investigated the evidence for molecular mechanisms
that caused these domain gains. In agreement with observations from the first
part - that changes preferentially occur at the termini - I have found that the
strongest contribution to gains of novel domains in proteins comes from gene
fusion through the joining of exons from adjacent genes into a novel gene unit.
Two other mechanisms that have been suggested to play a major role in the
evolution of animal proteins, retroposition and middle insertions through
intronic recombination, have a smaller role in comparison to gene fusions. Since
the majority of these domain gains are again observed after gene duplication,
this suggests a powerful mechanism for neofunctionalization after gene
Finally, in the last part of my thesis, I address a mechanism that increases
the number and variety of proteins in an organism – alternative splicing. In
particular, I investigate the functional consequences of tissue-specific alternative
splicing events. I found that tissue-specific splicing tends to affect exons that
encode protein regions without defined secondary or tertiary structure.
Importantly, it is known that these disordered regions frequently play a role in
protein interactions. In agreement with this, I observed significant enrichment of
tissue-specifically encoded protein segments in disordered binding peptides and
posttranslationally modified sites. A possible result of the finely regulated
alternative splicing of these segments is a tissue-specific rewiring of protein
network. In conclusion, both alternative splicing and domain shuffling can
increase proteome diversity. However, a protein with a new function can often
directly or indirectly shape the functions of other proteins in its environment.|
|Appears in Collections:||Theses - Sanger Instititute|
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