The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers
Abstract
:1. Introduction
2. The Key Features of Spiral Model of Accumulated Life Functions
- (a)
- The formation of new functionalities coupling with new organic codes via macroevolution;
- (b)
- The extension and modification of existing spiral functionalities via microevolution;
- (c)
- The improvement of constraint (control) over the already existing spiral functionalities and functions, i.e., improvement of control over intra-spiral functionalities/functions, which is schematically presented in this article by an increase in the squeeze of the spiral of life functions;
- (d)
- The improvement of genome stability by improving control over the functionalities of the bioenergetic layer, resulting in a decreased probability of the occurrence of macroevolution.
3. The Spiral Model of Cellular Evolution
3.1. The Spiral Model Can Integrate Key Life Functions
3.2. Cell Bioenergetic Problems as a Cause among Many of Cancer Transformation
3.3. A Phenomenon of Cancer Transformation as a Result of Disturbances in the Spiral of Life Functions
3.4. Chromosome Instability as a Common Cause of Cancer Transformation
3.5. The Cancer Supersystems Represent New Cellular Ecosystems
4. Information Management in the Spiral Model
5. Selected Aspects of Two-Phased Cancer Evolution
5.1. The Physical Restructuring of the Existing Genome Can Result from Either the Death or the Emergence of a New Life Form
5.2. Scenarios of Competition between Clones
5.3. Cancerous Microenvironment as a Stimulator of Macroevolution
5.4. Cancerous Tissue and Elevated Risk of Metastases Caused by Macroevolution
5.5. Cancer as a Phenomenon with Many Faces—Cancer Progression Is Not Simply Atavism
6. Conclusions and Future Directions
- (a)
- A series of two-phased evolutions are linked by the spiral model. With the establishment of major macroevolutionary innovations, more organic codes form, coupled with increased complexity. The preservation and further modification of these codes provides the mechanisms for long and stable microevolution, allowing populations to grow. Therefore, maintaining the integrity of the chromosome sets or genome is important for given species. In contrast, CIN can harm a species, potentially leading to the emergence of conditions such as cancer.
- (b)
- Macroevolution occurs rapidly, as indicated by the sudden color change, while microevolution is a much longer process, represented by the spiral maintaining the same color. The continuity of the spiral among different species is achieved by different organisms, which function as carriers of information. Specifically, for species with sexual reproduction, the sex function acts as a filter to preserve the karyotype coding, which, in turn, also preserves most of the organic codes [47,111,112]. In cancer, the continuity of the spiral is achieved by different populations of cells with different karyotypes. Comparing the phenotype and genotype profiles of cancer with those of the ancestor (normal cell), cancer cells often lose the constraints on normal cell regulation and collaboration, as well as genome integrity.
- (c)
- For all biological entities, whether independent organisms like humans or cellular organisms like cancers, existence is achieved through mechanisms of information creation, preservation, and amplification during the evolutionary process. For example, the success of organismal evolution depends on an individual’s physiological capability to organize and constrain cellular components for the individual’s function, while the success of cancer evolution depends on breaking down these constraints to form new cellular systems that can compete with the host. CIN is a key player in the conflicting relationship between the host and cancer. When the genome is stable, cancer has a lower chance of success, although the host also reduces its capability for cellular adaptation. When CIN is dominant, new cellular systems can more easily overcome constraints and become cancerous. This is why CIN is a common driver of most cancers. The discussion of bioenergetic disturbances fully supports this view, as many molecular mechanisms are linked to CIN. Indeed, the evolutionary mechanism of cancer, which encompasses the collection and combination of all individual molecular mechanisms, is proposed to unify the field.
- (d)
- During the normal evolution of organisms, when new cellular functionalities are added, the dominance of previously existing functionalities is often adjusted. For example, before typical chromosome formation, individual genes in bacteria might have been more dominant. After chromosome formation, the system-level inheritance takes precedence over the part-level inheritance, becoming an organizer to regulate and constrain the functions of individual genes. The increased organic codes also require genome stability to ensure their maintenance. During cancer evolution, CIN breaks outside the spiral of life functions, removing many constraints and allowing the abnormal activity of unicellular genes, for example. The newly formed genomes no longer follow the host’s system control.
- (e)
- The battle between the stable microevolution of hosts and the unstable life form of cancer is the very reason why eradicating cancer using powerful drugs proves to be so challenging. This underscores why a singular focus on eradication may be less effective, as treatment-induced crises can actually promote cancer by increasing the probability of macroevolution and, therefore, the opportunity for these unstable life forms to become more aggressive. Novel approaches to combat cancer should be grounded in the understanding of the two-phased evolution and effective information management, because inappropriate treatment may inadvertently harm the host by creating highly unstable genomes. These pharmaceutically created, more aggressive supersystems consist of a mixture of cells, both clonal and nonclonal, representing different stages of evolution. They become extremely challenging to fight, as each of these genetically distanced systems may require different pharmacological agents to eliminate them. Incorrectly established pharmaceutical agents may extinguish some systems, but can also lead to the stimulation of new cancer populations with altered dynamics of both macroevolution and microevolution.
- (f)
- Information management in cancer and host organisms offers new insights into cancer evolution. Cancers possess numerous abilities to generate new information during their evolution, without the constraints of sexual reproduction. This puts them on different competitive playing fields. Given the inherently chaotic nature of cancer evolution, determining the types of data to collect, how to prioritize research, at which phase, and on what scale of systems are still matters of ultimate importance and necessary to debate. For example, one alternative explanation for the mechanism of adaptive therapy [113,114] could be the reduction in genome chaos events. We anticipate that using moderate treatment to slow down microevolution without triggering massive genome chaos could be a new strategy for managing cancers in the future [3,4,31,84].
- (g)
- Genome chaos needs more mathematical understanding (Appendix A): it is challenging to describe genome chaos using current mathematical tools. Biological chaos, with its unique specificity, is much more complex than most physical systems. However, due to the involvement of developmental, physiological, and evolutionary constraints, its predictability can be greater than in physical systems under certain conditions. The question of how to incorporate these key differences into classical chaos theory requires further research. Nevertheless, an increasing number of papers discussing genome chaos from this perspective are being published [115].
- (h)
- The spiral model helps us to understand the mechanisms of both cancer and organismal evolution. Due to the constraints of the genome landscape, evolutionary selection aims to reduce changes in the host genome. In contrast, for successful cancer evolution, favoring system instability leads to the emergence of new systems, in which the supersystem or cancer ecosystem becomes more aggressive. This information is valuable for designing strategies to combat cancer without triggering genome chaos. An example of this would be paying more attention to treatment-induced drug resistance [72,84]. This approach is likely to explain the success of adaptive therapy as well [113,114], providing new prospects for more effective cancer treatments in the near future. One important mechanism of cancer-drug-treatment-induced resistance can be illustrated using the spiral model. The treatment can focus on either microevolution or macroevolution. Using moderate treatment, the cancer population can be reduced without triggering genome chaos. Even though the initial killing is less remarkable, the long-term benefit can be better. Harsh treatments aimed at eliminating all cancer cells can often trigger genome chaos, leading to short-term massive cell death. However, this aggressive treatment can simultaneously result in the emergence of new cancer systems, via rapid genome reorganization, which are drug-resistant and more aggressive. In a sense, treatment aimed at killing cancer cells can promote the success of cancer macroevolution, leading to drug resistance and aggressiveness. This mechanism can explain why aggressive treatment often has good short-term outcomes, but lacks significant long-term survival benefits (Figure 2).
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
- Genome as an Integrated System Rather than a Bag of Genes: The overall genomic architecture, defined by the karyotype (the complete set of chromosomes), is crucial for maintaining system identity, stability, and functionality.
- Karyotype Coding: Responsible for system inheritance, it organizes gene interactions by defining the genetic network structure. Alterations in karyotype coding play a key role in organismal and cancer evolution.
- Two-phased Evolution Unifies Macro- and Microevolution: Unlike the traditional assumption that macroevolution equals the accumulation of microevolution over time, the mechanisms of macro and microevolution differ. Macroevolution involves genome alterations, while microevolution involves gene mutations. This two-phased evolution model reconciles different molecular mechanisms for both genomics and evolution [109,134,135,136].
- Information Management: Traditional information research has overlooked information creation at the system level. Information preservation is crucial for ensuring self-organization into biological routines. Previously, research focused mainly on genetic code usage. The concept of information management reconciles genome and gene functions, providing a new perspective on evolution as information flow, which also drives evolution [31,32,38].
- New Perspective of Inheritance: The genome defines the bioinformation package, rather than genes, representing a holistic view of genetic information. There is a complex and dynamic relationship between multiple scales of genomic and non-genomic inheritance, with the environment serving as an important information context. All inheritance is fuzzy, coding a spectrum of potential phenotypes rather than a defined phenotype, explaining the gaps between genotype and phenotype. Fuzzy inheritance and environmental dynamics form the basis of biological heterogeneity [4].
- New Evolutionary Perspective: Evolutionary constraint is the major function of microevolution. The function of sex is the preservation of system inheritance [56,112]. Developmental and physiological mechanisms also serve as constraints. Genome constraint and gene dynamics are key to understanding the process of somatic change without germline change under “normal” environments, until new genomes form under crisis. This perspective explains the importance of massive extinction events that drive rapid evolution on Earth and aggressive cancer following maximal treatment [32,84,137,138,139,140].
- Redefined Functions of Evolution: In the macroevolutionary phase, chromosomal instability (CIN), either inherited or induced (often arising from environmental crises, including hybridization and accidental access to foreign genomes), promotes genome reorganization via chaos followed by macroevolution. Once new systems or species are formed and survive macro-selection, the function of microevolution is mainly to preserve these systems through biological mechanisms, such as copying or amplifying individuals, where stability is key. Many factors, including selection, as well as physical and developmental constraints, are responsible for such stability. Without it, there is no biological evolution. Therefore, by and large, the evolutionary process is about the conservation of information and its carriers, the organisms, unlike the traditional assumption that evolution is mainly about evolving. With increased complexity in the Earth’s history, more layers of regulation will be required. This is why the spiral can gain more layers with increased complexity and biofunctions. For cancer to be successful within stable organisms, a high level of CIN is constantly needed to break the multiple system constraints. Under stress, more factors can contribute to cancer. Increased reports support this idea [47,141].
- Clinical Implications: Karyotype-defined genome architecture has significant implications for disease diagnosis, treatment, and prevention. Strategies targeting genomic stability and the overall karyotype may be more effective than focusing solely on individual gene mutations. For both cancer research and medical use, prioritizing treatment options based on scales of genomics and phases of evolution is crucial [33,34,35,84,142,143,144,145].
- Information Creation: This mainly refers to system-level information creation through genome-chaos-mediated karyotype reorganization.
- Information Maintenance or Preservation: Karyotype information is primarily preserved through the functions of sex, the developmental process, and genome integrity.
- Information Modification and Transmission: This involves the accurate replication and distribution of genetic information during cell division and reproduction.
- Information Utilization: This encompasses the processes by which genetic information is accessed and used to produce functional molecules and carry out cellular processes.
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Kasperski, A.; Heng, H.H. The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers. Int. J. Mol. Sci. 2024, 25, 9163. https://doi.org/10.3390/ijms25179163
Kasperski A, Heng HH. The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers. International Journal of Molecular Sciences. 2024; 25(17):9163. https://doi.org/10.3390/ijms25179163
Chicago/Turabian StyleKasperski, Andrzej, and Henry H. Heng. 2024. "The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers" International Journal of Molecular Sciences 25, no. 17: 9163. https://doi.org/10.3390/ijms25179163