“…In turn, the early embryonal development in mammals also bears the phylogenetic features of the transition from unicellular to multicellular organisms. This transition evolved little new genes and it was mostly operating with multi-nuclearity, transient colonial forms, ploidy cycles [145,146], chromatin diminution [147], facultative sex [148], and asexual reproduction [149,150]. Interestingly, the earliest tumours were discovered within the same evolutionary forms, in basic metazoan Hydra, the authors concluded: "cancer is as old as multicellular life on Earth" [151].…”
Section: Cancer Cells Recapitulate the Stress-adaptive Programs Of Unmentioning
The apparent lack of success in curing cancer that was evidenced in the last four decades of molecular medicine indicates the need for a global re-thinking both its nature and the biological approaches that we are taking in its solution. The reductionist, one gene/one protein method that has served us well until now, and that still dominates in biomedicine, requires complementation with a more systemic/holistic approach, to address the huge problem of cross-talk between more than 20,000 protein-coding genes, about 100,000 protein types, and the multiple layers of biological organization. In this perspective, the relationship between the chromatin network organization and gene expression regulation plays a fundamental role. The elucidation of such a relationship requires a non-linear thermodynamics approach to these biological systems. This change of perspective is a necessary step for developing successful 'tumour-reversion' therapeutic strategies.
“…In turn, the early embryonal development in mammals also bears the phylogenetic features of the transition from unicellular to multicellular organisms. This transition evolved little new genes and it was mostly operating with multi-nuclearity, transient colonial forms, ploidy cycles [145,146], chromatin diminution [147], facultative sex [148], and asexual reproduction [149,150]. Interestingly, the earliest tumours were discovered within the same evolutionary forms, in basic metazoan Hydra, the authors concluded: "cancer is as old as multicellular life on Earth" [151].…”
Section: Cancer Cells Recapitulate the Stress-adaptive Programs Of Unmentioning
The apparent lack of success in curing cancer that was evidenced in the last four decades of molecular medicine indicates the need for a global re-thinking both its nature and the biological approaches that we are taking in its solution. The reductionist, one gene/one protein method that has served us well until now, and that still dominates in biomedicine, requires complementation with a more systemic/holistic approach, to address the huge problem of cross-talk between more than 20,000 protein-coding genes, about 100,000 protein types, and the multiple layers of biological organization. In this perspective, the relationship between the chromatin network organization and gene expression regulation plays a fundamental role. The elucidation of such a relationship requires a non-linear thermodynamics approach to these biological systems. This change of perspective is a necessary step for developing successful 'tumour-reversion' therapeutic strategies.
“…The large free-living amoebae, such as the Amoeba proteus group, have been studied for more than a century and a half, with no indication of sex, despite such close inspection. [70] There is a similar lack of data on sexual processes in other well-studied amoebae, including Naegleria [71] and Acanthamoeba. [72] That some protists exist with no or very little indication of a sexual or parasexual cycle poses the question of how, despite Muller's ratchet and Kondrashov's hatchet, this is possible.…”
Section: Nullification Of Muller's Ratchet and Kondrashov's Hatchet Bmentioning
confidence: 99%
“…[75] It has been suggested that cyclic polyploidy may act to minimize the deleterious effects of asexuality, [76] and in the A. proteus group. [70] While others suggest that polyploidy dilutes the effect of deleterious mutations while permitting fixation of advantageous mutations, [77] yet others have argued that polyploidy increases the mutation rate to an optimum. [78] On balance it seems most likely that polyploidy reduces mutations through correction by HR.…”
Section: Nullification Of Muller's Ratchet and Kondrashov's Hatchet Bmentioning
confidence: 99%
“…The amoeba may divide mitotically to produce B) two daughter cells, each with half the original genome copy number, but there may be additional DNA loss in the A. proteus group. [70] When an amoeba (A) forms D) a viable cyst, MSGs are upregulated causing a decrease in ploidy in Entamoeba. [93] If, after depolyploidization, a nascent cyst receives a fatal mutation (red diagonal bar), then it is non-viable (C), thus removing this mutant gene from the population.…”
Section: As You Were: Meiosis Evolved From Mitosis Incorporating Hr Mmentioning
The notion that eukaryotes are ancestrally sexual has been gaining attention. This idea comes in part from the discovery of sets of "meiosis-specific genes" in the genomes of protists. The existence of these genes has persuaded many that these organisms may be engaging in sex, even though this has gone undetected. The involvement of sex in protists is supported by the view that asexual reproduction results in the accumulation of mutations that would inevitably result in the decline and extinction of such lineages. It is argued that this phenomenon can be obviated by polyploidy and that the "meiosis-specific genes" are used in other processes, including polyploidy control and homologous recombination, independent of meiosis. These phenomena account for the finding that these genes are expressed in cultures devoid of apparent cell fusion events. Hence, it is also proposed that asexual, and not sexual, reproduction is the ancestral condition.
“…The same relates to somatic tumours of the mammals -like protists, they are immortal and we still do not have an answer, why? Interestingly, many agamic protists undergo cyclic polyploidy [9,10]. In turn, polyploidy and aneuploidy in human cancer cells are associated with genome reprogramming [3,11].…”
Triploidy in cancer is associated with poor prognosis but its origins remain unclear. Here, we attempted to differentiate between random chromosomal and whole genome origins of cancer triploidy. malignant and 5 benign tumour cohorts (2928 karyotypes) extracted from the Mitelman Database, comparing the triploid fraction was observed in all malignant tumour types, being especially high in seminoma. For all tumour types, X XXY, correlated strongly with near-diploidy, and did not correlate with near component with a doubled X especially notable in colon adenoma. Principal Component Analysis revealed a non random correlation structure shaping the X tumour types. We suggest that doubling of the maternal genome followed by pedogamic fusion with a paternal genome (a possible mimic of the fertilization aberration, 69, XXY digyny) associated with meiotic reprogramming may be responsible for the observed rearrangements of genome complements leading to cancer triploidy. The relatively frequent loss of the Y-
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