Computation in Living Cells: Gene Assembly in Ciliates (Natural Computing Series) [Englisch] [Gebundene Ausgabe]

The use of living processes to generate grammars, artificial reasoning patterns, or computational algorithms is now a broad area of research and has been labeled as `bio-inspired computing'. Bio-inspired computing includes such fields as evolutionary programming, genetic algorithms, evolutionary strategies, cell grammar, and DNA computing. As a branch of DNA computing, this book is unique in that it tries to develop a formal theory of gene assembly in living cells by studying the case of ciliates, which are single-celled eukaryotic organisms possessing two different kinds of nuclei, namely the `micronucleus' and `macronucleus.' Gene assembly involves the transformation of the genome of the micronucleus into the genome of the macronucleus. The book therefore does not address the ability of the computational model of ciliates to solve difficult (combinatorial) problems, but rather, as the authors emphasize in the preface, emphasizes the gene assembly process itself. They are interested in the different kinds of genes that can be generated during gene assembly, along with the different strategies used in gene assembly. The book is interesting, in spite of the lack of practical applications for computing as of yet. It remains to be seen whether studies like the one in this book will result in practical realizations of (in vivo) DNA computing.

After a brief review of the biology of the cell in chapter 1, the authors give more details of the biology of ciliates in chapter 2. Of particular importance are the MDSs (macronuclear destined segments), which are DNA segments created during evolution of segments of IESs (internal eliminated segments), the latter being nongenetic DNA. The authors describe as `natural computing' the conversion of micronucleus into a macronucleus. This involves the elimination of the IESs and the eventual splicing of MDSs in an "orthodox" order. The `gene scrambling' process described by the authors that occurs in a particular group of ciliates called `stichotrichs' is fascinating and they give a brief discussion of the possible evolutionary advantages of this process.

The authors develop the formal model for gene assembly in ciliates using various levels of abstraction. The actual assembly process involves three molecular operations, namely `loop', `hairpin', and `double-loop' recombination, abbreviated as `ld', `hi', and `dlad' in the book. All of these operations can work in parallel and in their description the pairs of repeats are referred to as `pointers' (they "point" the way for MDS joining). For stichotrichs, the macronuclear formation takes place by homologous recombination between pointers. The authors mention, interestingly, that it is an open question as to how two identical segments recognize each other. In their formal models of gene assembly, the authors use the notion of a `intermediate' gene, which is obtained during the process of assembling the macromolecular gene. The process of formalization involves first neglecting the identity of the IESs to form `MDS arrangements' and then to `MDS descriptors', the latter being strings of pairs of symbols representing pointers. The MDS descriptors also involve the use of symbols indicating the beginning and ending of the micronuclear gene. This is simplified even further by using `legal strings' consisting of only pointers.

The most helpful feature of the book is the more precise mathematical formulations that the authors give to the processes of gene assembly. This involves viewing DNA sequences as (cyclic) graphs, with the important concept of an alternating Hamiltonian path arising during this discussion. The ld, hi, and dlad operations are then rewriting rules for MDS descriptors, with the latter being defined in terms of `MDS arrangements'. Of particular importance are `orthodox' MDS arrangements, which do not contain any inversions and which are in their "natural" order. A signed permutation of an orthodox arrangement is called `realistic' and the authors show that each realistic MDS descriptor has a successful assembly strategy (i.e. an assembly strategy that results in the beginning and ending symbols).

The simplification of the MDS descriptors using legal strings arises when the parentheses and markers are deleted. This removal process is represented by a "morphism", with a legal string being called `realistic' if there exists a realistic MDS descriptor that gets mapped by this morphism to the string. Since structural information about the molecule is lost in this simplification, it is important to characterize those pairs of micronuclear arrangements that are described by the same realistic legal string. Strings that come from a particular alphabet are called `realizable' if they are isomorphic to a realistic legal string. More interesting are the double occurrence strings that are also signed, for the authors show that they can be realized if and only if their graph has an alternating Hamiltonian path. The authors show in detail how the rewriting rules ld, hi, and dlad on legal strings result in what they call `string pointer reduction systems.' In contrast with the case of MDS descriptors there are only three types of rules for legal strings. The authors prove that there is an injection between the operations for realistic MDS descriptors and the operations on legal strings.

Without grammatical representations of the authors' constructions in terms of formal language theory or computational linguistics, it might be difficult to realize them in a computing machine. Their results though are very helpful to mathematicians who need a more compact and simplified way of thinking about gene assembly than what is usually encountered in the biological literature. Many mathematicians and computer scientists have in recent years been highly motivated to enter the field of computational biology or bioinformatics both because of its inherent fascinations and in its challenges. The content of this book will definitely help them on their way, and give hints on how more complicated gene assemblies. The authors point to areas that need further study, such as the need to characterize when a particular assembly strategy is more feasible than another one, and the need for better methods for comparing a particular strategy to another one. These questions among others are ample material for those readers interested in entering this particular field of natural computing.