scholarly journals Trade-off between reducing mutational load and increasing commitment to differentiation determines tissue organization

2020 ◽  
Author(s):  
Márton Demeter ◽  
Imre Derényi ◽  
Gergely J. Szöllősi
Keyword(s):  
Tumor Suppressor Genes ◽  
Mutation Accumulation ◽  
Specific Level ◽  
Trade Off ◽  
Somatic Evolution ◽  
Tissue Organization ◽  
Copy Numbers ◽  
Magnitude Variation ◽  
Species Specific ◽  
Risk Of Cancer

AbstractSpecies-specific differences control cancer risk across orders of magnitude variation in body size and lifespan, e.g., by varying the copy numbers of tumor suppressor genes. It is unclear, however, how different tissues within an organism can control somatic evolution despite being subject to markedly different constraints but sharing the same genome. Hierarchical differentiation, characteristic of self-renewing tissues, can restrain somatic evolution both by limiting divisional load, thereby reducing mutation accumulation, and by increasing the cells’ commitment to differentiation, which can “wash out” mutants. Here, we explore the organization of hierarchical tissues that have evolved to limit their lifetime risk of cancer to a tissue-specific level. Analytically estimating the likelihood of cancer, we demonstrate that a trade-off exists between mutation accumulation and the strength of washing out. This result explains the differences in the organization of widely different hierarchically differentiating tissues, such as the colon and the blood.

scholarly journals A compartment size dependent selective threshold limits mutation accumulation in hierarchical tissues

2019 ◽  
Author(s):  
Daniel Grajzel ◽  
Imre Derenyi ◽  
Gergely J Szollosi
Keyword(s):  
Selective Advantage ◽  
Cell Number ◽  
Significant Determinant ◽  
Size Dependent ◽  
Somatic Evolution ◽  
Tissue Organization ◽  
Tissue Size ◽  
Risk Of Cancer ◽  
Proliferative Advantage ◽  
Fundamental Mechanism

Cancer is a genetic disease fueled by somatic evolution. Hierarchical tissue organization can slow somatic evolution by two qualitatively different mechanisms: by cell differentiation along the hierarchy "washing out" harmful mutations (Nowak et al. 2003, Werner et al. 2013) and by limiting the number of cell divisions required to maintain a tissue (Derenyi and Szollosi 2017). Here we explore the effects of compartment size on somatic evolution in hierarchical tissues by considering cell number regulation that acts on cell division rates such that the number of cells in the tissue has the tendency to return to its desired homeostatic value. Introducing mutants with a proliferative advantage we demonstrate the existence of a third fundamental mechanism by which hierarchically organized tissues are able to slow down somatic evolution. We show that tissue size regulation leads to the emergence of a threshold proliferative advantage, below which mutants cannot persist. We find that the most significant determinant of the threshold selective advantage is compartment size, with the threshold being higher the smaller the compartment. Our results demonstrate that in sufficiently small compartments even mutations that confer substantial proliferative advantage cannot persist, but are expelled from the tissue by differentiation along the hierarchy. The resulting selective barrier can significantly slow down somatic evolution and reduce the risk of cancer by limiting the accumulation of mutations that increase the proliferation of cells.

scholarly journals A compartment size-dependent selective threshold limits mutation accumulation in hierarchical tissues

2020 ◽  
Vol 117 (3) ◽  
pp. 1606-1611 ◽  
Author(s):  
Dániel Grajzel ◽  
Imre Derényi ◽  
Gergely J. Szöllősi
Keyword(s):  
Selective Advantage ◽  
Cell Number ◽  
Significant Determinant ◽  
Size Dependent ◽  
Somatic Evolution ◽  
Tissue Organization ◽  
Tissue Size ◽  
Risk Of Cancer ◽  
Proliferative Advantage ◽  
Fundamental Mechanism

Cancer is a genetic disease fueled by somatic evolution. Hierarchical tissue organization can slow somatic evolution by two qualitatively different mechanisms: by cell differentiation along the hierarchy “washing out” harmful mutations and by limiting the number of cell divisions required to maintain a tissue. Here we explore the effects of compartment size on somatic evolution in hierarchical tissues by considering cell number regulation that acts on cell division rates such that the number of cells in the tissue has the tendency to return to its desired homeostatic value. Introducing mutants with a proliferative advantage, we demonstrate the existence of a third fundamental mechanism by which hierarchically organized tissues are able to slow down somatic evolution. We show that tissue size regulation leads to the emergence of a threshold proliferative advantage, below which mutants cannot persist. We find that the most significant determinant of the threshold selective advantage is compartment size, with the threshold being higher the smaller the compartment. Our results demonstrate that, in sufficiently small compartments, even mutations that confer substantial proliferative advantage cannot persist, but are expelled from the tissue by differentiation along the hierarchy. The resulting selective barrier can significantly slow down somatic evolution and reduce the risk of cancer by limiting the accumulation of mutations that increase the proliferation of cells.

scholarly journals Janthinobacterium CG23_2: Comparative Genome Analysis Reveals Enhanced Environmental Sensing and Transcriptional Regulation for Adaptation to Life in an Antarctic Supraglacial Stream

2019 ◽  
Vol 7 (10) ◽  
pp. 454
Author(s):  
Markus Dieser ◽  
Heidi J. Smith ◽  
Thiruvarangan Ramaraj ◽  
Christine M. Foreman
Keyword(s):  
Transcriptional Regulation ◽  
Extreme Environment ◽  
Ecological Niches ◽  
Genome Plasticity ◽  
Functional Categories ◽  
Environmental Sensing ◽  
Copy Numbers ◽  
Environmental Extremes ◽  
Species Specific ◽  
Extracellular Environment

As many bacteria detected in Antarctic environments are neither true psychrophiles nor endemic species, their proliferation in spite of environmental extremes gives rise to genome adaptations. Janthinobacterium sp. CG23_2 is a bacterial isolate from the Cotton Glacier stream, Antarctica. To understand how Janthinobacterium sp. CG23_2 has adapted to its environment, we investigated its genomic traits in comparison to genomes of 35 published Janthinobacterium species. While we hypothesized that genome shrinkage and specialization to narrow ecological niches would be energetically favorable for dwelling in an ephemeral Antarctic stream, the genome of Janthinobacterium sp. CG23_2 was on average 1.7 ± 0.6 Mb larger and predicted 1411 ± 499 more coding sequences compared to the other Janthinobacterium spp. Putatively identified horizontal gene transfer events contributed 0.92 Mb to the genome size expansion of Janthinobacterium sp. CG23_2. Genes with high copy numbers in the species-specific accessory genome of Janthinobacterium sp. CG23_2 were associated with environmental sensing, locomotion, response and transcriptional regulation, stress response, and mobile elements—functional categories which also showed molecular adaptation to cold. Our data suggest that genome plasticity and the abundant complementary genes for sensing and responding to the extracellular environment supported the adaptation of Janthinobacterium sp. CG23_2 to this extreme environment.

Deflighting zoo birds and its welfare considerations

2020 ◽  
Vol 29 (1) ◽  
pp. 69-80 ◽  
Author(s):  
L Reese ◽  
M Ladwig-Wiegard ◽  
L von Fersen ◽  
G Haase ◽  
H Will ◽  
...  
Keyword(s):  
Public Interest ◽  
Surgical Techniques ◽  
Bird Species ◽  
Scientific Data ◽  
Evidence Based ◽  
Specific Level ◽  
Welfare Implications ◽  
Reduce Risk ◽  
Species Specific ◽  
Over Time

For over a century the practice of deflighting has taken place in zoological collections in order to ensure birds remain in open-topped enclosures. Over time, efforts have been made to improve or develop new (surgical) techniques, reduce risk of complications during deflighting and minimise stress and pain during the procedure. However, increased public interest in issues of animal welfare has coincided with a questioning of the practice of removing a birds ability to fly. The ensuing debate, which continues to progress among a variety of differing stakeholders, has led to various legislative adjustments across a number of countries. Despite significant legislation, the dialogue has been both subjective and highly emotive. A plethora of opinions exist as to why deflighting should be outlawed, why it is necessary, or how it has the potential to improve a birds living conditions. However, most are based on assumption or issues unrelated to welfare. To the authors knowledge, to date, no scientific data have been published on the welfare implications of deflighting for the commonly deflighted bird species, such as waterfowl, flamingos (Phoenicopteridae), pelicans (Pelecanidae), storks (Ciconiidae), cranes (Gruidae) and herons (Ardeidae). The aim of this study is to present an overview of the relevance of deflighting to zoo husbandry, the species primarily affected, the techniques currently in use, the legality in differing countries and the extent of scientific knowledge as regards potential ethological and welfare concerns. An urgent need for evidence-based studies is highlighted, to further inform this practice at a species-specific level.

scholarly journals Developmental expression of the 412 retrotransposon in natural populations of D. melanogaster and D. simulans

2000 ◽  
Vol 76 (3) ◽  
pp. 217-226 ◽  
Author(s):  
N. BORIE ◽  
C. LOEVENBRUCK ◽  
C. BIEMONT
Keyword(s):  
Expression Pattern ◽  
Copy Number ◽  
Developmental Stages ◽  
Population Sample ◽  
Natural Populations ◽  
Developmental Expression ◽  
Regulatory Sequences ◽  
Copy Numbers ◽  
Species Specific ◽  
Very High

We analysed the pattern of expression of retrotransposon 412 through developmental stages in various populations of Drosophila simulans and D. melanogaster differing in 412 copy number. We found that the 412 expression pattern varied greatly between populations of both species, indicating that such patterns were not entirely species-specific. In D. simulans, total transcripts increased with number of 412 copies in the chromosomes when this number was low, and then decreased for high copy numbers. D. melanogaster, which has a higher 412 copy number than D. simulans, had overall a lower global 412 expression, but again showed variation in 412 expression pattern between populations. These results suggest that in populations of D. simulans with low 412 copy number, the expression pattern of this element depends not only on copy number but also on host cellular regulatory sequences near which the elements were inserted. In D. simulans populations with high copy number overall transcription was on the contrary globally repressed, as observed in D. melanogaster. A population from Canberra (Australia) which had a very high 412 copy number was found to be associated with very high expression of 412 over all developmental stages, suggesting that the above 412 expression regulation processes are overcome in this population sample. The analysis of hybrids between geographically distinct populations of D. simulans showed that 412 expression was trans-regulated differently according to developmental stages, implying complex interactions between the 412 element and stage-specific host genes.

scholarly journals Forest before the trees in the aquatic world: global and local processing in teleost fishes

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9871
Author(s):  
Maria Santacà ◽  
Maria Elena Miletto Petrazzini ◽  
Marco Dadda ◽  
Christian Agrillo
Keyword(s):  
Global Analysis ◽  
Local Information ◽  
Visual Illusions ◽  
Specific Level ◽  
Ecological Adaptations ◽  
Visual Inputs ◽  
Different Shapes ◽  
Species Specific ◽  
Global And Local ◽  
Perceptual Systems

Background The study of illusory phenomena is important to understanding the similarities and differences between mammals and birds’ perceptual systems. In recent years, the analysis has been enlarged to include cold-blooded vertebrates, such as fish. However, evidence collected in the literature have drawn a contradictory picture, with some fish species exhibiting a human-like perception of visual illusions and others showing either a reversed perception or no susceptibility to visual illusions. The possibility exists that these mixed results relate to interspecific variability in perceptual grouping mechanisms. Therefore, we studied whether fish of five species exhibit a spontaneous tendency to prioritize a global analysis of the visual scene—also known as global-to-local precedence—instead of focusing on local details. Methods Using Navon-like stimuli (i.e., larger recognisable shapes composed of copies of smaller different shapes), we trained redtail splitfin, zebrafish, angelfish, Siamese fighting fish and three spot gourami to discriminate between two figures characterized by congruency between global and local information (a circle made by small circles and a cross made by small crosses). In the test phase, we put global and local cues (e.g., a circle made by small crosses) into contrast to see whether fish spontaneously rely on global or local information. Results Like humans, fish seem to have an overall global-to-local precedence, with no significant differences among the species. However, looking at the species-specific level, only four out of five species showed a significant global-to-local precedence, and at different degrees. Because these species are distantly related and occupy a broad spectrum of ecological adaptations, we suggest that the tendency to prioritize a global analysis of visual inputs may be more similar in fish than expected by the mixed results of visual illusion studies.

scholarly journals Supernumerary B Chromosomes and Plant Genome Changes: A Snapshot of Wild Populations of Aegilops speltoides Tausch (Poaceae, Triticeae)

2020 ◽  
Vol 21 (11) ◽  
pp. 3768 ◽  
Author(s):  
Imad Shams ◽  
Olga Raskina
Keyword(s):  
B Chromosomes ◽  
Plant Genome ◽  
Aegilops Speltoides ◽  
Genomic Component ◽  
Dna Damage And Repair ◽  
Real Time Quantitative Pcr ◽  
Copy Numbers ◽  
Number Dynamics ◽  
Species Specific ◽  
The Impact

In various eukaryotes, supernumerary B chromosomes (Bs) are an optional genomic component that affect their integrity and functioning. In the present study, the impact of Bs on the current changes in the genome of goatgrass, Aegilops speltoides, was addressed. Individual plants from contrasting populations with and without Bs were explored using fluorescence in situ hybridization. In parallel, abundances of the Ty1-copia, Ty3-gypsy, and LINE retrotransposons (TEs), and the species-specific Spelt1 tandem repeat (TR) in vegetative and generative spike tissues were estimated by real-time quantitative PCR. The results revealed: (i) ectopic associations between Bs and the regular A chromosomes, and (ii) cell-specific rearrangements of Bs in both mitosis and microgametogenesis. Further, the copy numbers of TEs and TR varied significantly between (iii) genotypes and (iv) different spike tissues in the same plant(s). Finally, (v) in plants with and without Bs from different populations, genomic abundances and/or copy number dynamics of TEs and TR were similar. These findings indicate that fluctuations in TE and TR copy numbers are associated with DNA damage and repair processes during cell proliferation and differentiation, and ectopic recombination is one of the mechanisms by which Bs play a role in genome changes.

scholarly journals Comparative Dissection of Three Giant Genomes: Allium cepa, Allium sativum, and Allium ursinum

2019 ◽  
Vol 20 (3) ◽  
pp. 733 ◽  
Author(s):  
Vratislav Peška ◽  
Terezie Mandáková ◽  
Veronika Ihradská ◽  
Jiří Fajkus
Keyword(s):  
Allium Cepa ◽  
Dna Repeats ◽  
Allium Species ◽  
Important Species ◽  
Satellite Sequences ◽  
Copy Numbers ◽  
Species Specific ◽  
Interspecific Breeding

Knowledge of the fascinating world of DNA repeats is continuously being enriched by newly identified elements and their hypothetical or well-established biological relevance. Genomic approaches can be used for comparative studies of major repeats in any group of genomes, regardless of their size and complexity. Such studies are particularly fruitful in large genomes, and useful mainly in crop plants where they provide a rich source of molecular markers or information on indispensable genomic components (e.g., telomeres, centromeres, or ribosomal RNA genes). Surprisingly, in Allium species, a comprehensive comparative study of repeats is lacking. Here we provide such a study of two economically important species, Allium cepa (onion), and A. sativum (garlic), and their distantly related A. ursinum (wild garlic). We present an overview and classification of major repeats in these species and have paid specific attention to sequence conservation and copy numbers of major representatives in each type of repeat, including retrotransposons, rDNA, or newly identified satellite sequences. Prevailing repeats in all three studied species belonged to Ty3/gypsy elements, however they significantly diverged and we did not detect them in common clusters in comparative analysis. Actually, only a low number of clusters was shared by all three species. Such conserved repeats were for example 5S and 45S rDNA genes and surprisingly a specific and quite rare Ty1/copia lineage. Species-specific long satellites were found mainly in A. cepa and A. sativum. We also show in situ localization of selected repeats that could potentially be applicable as chromosomal markers, e.g., in interspecific breeding.

scholarly journals The Evolution of Human Cancer Gene Duplications across Mammals

2020 ◽  
Author(s):  
Marc Tollis ◽  
Aika K. Schneider-Utaka ◽  
Carlo C. Maley
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Tumor Suppressor Genes ◽  
Human Tumor ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Gene Copy ◽  
Cancer Gene ◽  
Suppressor Genes ◽  
Copy Numbers

AbstractCancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species’ cancer gene copy number and it’s longevity, but not body size, contrary to predictions from Peto’s Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.

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