Cancer as a script and possible implications on workings of genome

Functional network of neoplastic cancer metasignature genes

This network shows distinct sub-networks. The neoplastic cancer metasignature contains 69 genes.

Functional network of undifferentiated cancer metasignature genes

This figure shows a cohesive central network with no distinct sub-networks.The undifferentiated cancer metasignature contains 67 genes.

Functional network of combined cancer metasignature genes

A central network is prominent. Both lists of the metasignature genes were combined to produce this functional network. This network is similar to undifferentiated network indicating genomic favour for progression from neoplastic state to the undifferentiated.

Central loop execution delayed by the influence of side loops

Each circle represents a dynamic loop which is executed. The thicker circles represent networks which are highly expressed and the thinner circles represent reduced expression or loop execution. Each overlapping circle influences the circle which it overlaps. So for continuous execution of the central loop the smaller side loops have to execute and collapse allowing the control to proceed. In functional network of the neoplastic cancer metasignature genes the side loops are stronger and execute faster hence they are prominently observed but the central loop is delayed which makes it inconspicuous in expression profiling. One has to imagine this and the next figure as dynamic constructs with constantly rotating circles indicating generation and collapse of loops.

Central loop executes rapidly due to weak side loops

The functional networks of the undifferentiated and the combined cancer metasignature genes show a prominent central loop because of the inability of weak side loops to delay it. The weak side loops are obscured and the central loop is detected prominently. Please see legend of figure 4 for further explanation.

Refinement of side loops halts the central loop in cell differentiation

Each consecutive division before the cell enters growth arrest refines a specific pattern of side loops which helps to achieve precision in function yielding highly specialised cell. The side loop pattern of the progenitor cell is broken progressively in the consecutive divisions. The polishing of specific side loops is represented by thinning or the thickening of the lines which reach out from the centre to the edges of a cell.

Evolution and genomic scripts in tandem

Each figure represents the total space available and the dashed boundaries represent the biosphere. Each pocket of the biosphere is the environment, the cell and the genomic script taken together as one. Sometimes environment effects the cells and cells respond with resistance by absorbing stimuli or by shifting the script. The response then effects the environment there by changing it to increased suitability to the organism. This new environment may then provide fertile ground for further evolution. Figure A to C: Early earth may have had pocket biospheres with extreme conditions. These pockets contained life adapted to the extreme conditions of the given environment. As time passed these could have amalgamated and some could have disappeared altogether. Figure D: shows an amalgamated pocket. Merger of the pockets with different conditions could have resulted in a new environment. The merger of the pockets could have been greatly helped by the formation of the first ocean which has been coloured blue in the figure. Figure E: the pocket grows large to cover most of the available space. Organisms with rigid scripts move to the edges where conditions are similar to the preceding environments. The extended biosphere gives rise to the flexible script which enables the organisms to drift off from their mother habitats and explore. Figure F: newly available environmental freedom helps cellular experimentation probably propelling the birth of multicellularity. Figure G and H: these newly evolved pockets merge or disappear or remain as they are. Figure I: the merged pocket increases in size as much as allowed. The well adapted species which favour rigidity remain confined to the edges of their environment. Figure J to L: these figures show the evolutionary process moving forward with repeating pattern.

Multicellular organisms evolved by merging individual scripts

Each cell is represented by a circle and its genomic script by the outer circle of each cell. Outer circle area has been shaded in different colours indicating different scripts. Simple multicellular organisms probably evolved by merging the individual scripts of their cells. The merged script acts like a single script compelling the individual cells into multicellular coordination.

Genomic script diverged into three broad routes

The genomic script seems to have diverged into three broad routes. The first diverging point resulted in rigid scripts and flexible scripts. The rigid script is a specialist script which is perfectly adapted to the habitat whereas the flexible script allowed exploration of the available biosphere. A third route which enabled the multicellular evolution was the merger of the scripts which necessitated the binding of DNA by placing tight controls over it.

An evolutionary click represents the genome stable state

The scale on the left represents prokaryotic genomic stable states and the scale on the right represents the eukaryotic genomic stable states. The scale has standard units for variation as the values. These are arbitrary and for representative purpose only. Each band on the scale represents a genomic stable state or a click where further change in the genome is discouraged. The bands are wider if the organism's genomic stable state is flexible and occur at longer distances on the evolutionary scale. The flexibility of the script enables prokayotic species to have wide clicks and sometimes two different species with highly similar genome may have overlapping stable states. In the case of multicellular eukaryotes the clicks are short and at the same time occur at shorter distances which allows distinct species to exist at short distances probably because of the tight control placed over the genome.

List of cancer metasignature genes