Evolution of New Inheritance Mechanisms

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Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Type I and type II CIN: CIN can be classified into two types based on its involved molecular mechanisms. Type I CIN is directly linked to the maintenance of genome integrity within the chromosomal cycle, including the chromosomal machinery, checkpoints, and repair systems (see Table 3). Type I CIN is often detected in chromosome instability syndromes which provide good examples of direct “ molecular causative relationship ” between identified genes and CIN. However, mutations to type I genes are rare and they do not explain sporadic cancer. In contrast, the mechanisms of type II CIN are often associated with non-genetic factors such as the micro-environment and physiological processes, which do not have a direct molecular causative explanation. The diverse type II mechanisms all share one common feature: they are involved in the cellular system ’ s response to stress, increasing heritable changes [50]. Fuzzy inheritance: In contrast to the gene theory, which states that a gene codes for a specific, fixed phenotype, the genome theory suggests that most genes code for a range of potential phenotypes. From this “ fuzzy ” range of phenotypes, the respective environment can then allow the best- suited status to be “ chosen ” [4, 37, 59]. For example, the gene for pea color codes for an entire potential spectrum of colors, from yellow to intense green (including blends of yellow and green, or green with yellow spots), not just two fixed, distinctive colors (yellow or intense green). In cancer, the emergence of “ genomic context ” adds yet another layer of complexity and instability that pushes fuzzy inheritance ’ s dynamics to a maximal status. Macro-and micro-cellular evolution: Macro-cellular evolution refers to karyotype change-mediated somatic cell evolution, which alters the genome context of a given cellular system. In contrast, micro-cellular evolution refers to gene/epigene change-mediated evolution, which modifies a given cellular system within the same karyotype. Macroevolution and microevolution respectively refer to organismal evolution at the above- species level and at the population level within a species.
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Lamarck, Evolution, and the Inheritance of Acquired Characters

Lamarck, Evolution, and the Inheritance of Acquired Characters

Here then is another reason to qualify both the common association of Lamarck’s name with the idea of the inheri- tance of acquired characters and the equally familiar con- trast between Lamarck’s idea of the inheritance of acquired characters with Darwin’s idea of natural selection. It was Darwin, not Lamarck, who offered a theory to explain how characters acquired as the result of use and disuse were transmitted from one generation to the next. It was also Darwin, as we have seen, who allowed that he had provided more evidence on the effects of use and disuse than anyone before him. Curiously enough, to add another historical irony (or perhaps even indignity) when it comes to Lamarck and the idea of the inheritance of acquired characters, in the whole of Darwin’s Variation of Animals and Plants under Domestication, where Darwin offered his many examples of the effects of use and disuse, he never once mentioned Lamarck’s name. It might be said that Darwin outdid Lamarck at what is typically taken to have been Lamarck’s own game but never acknowledged Lamarck in the process. What we have said thus far does not exhaust all the historical ironies with respect to the various ways Lamarck’s name has figured in discussions of how evolution works. We will leave aside here the decades immediately after Darwin’s death, when August Weismann launched his assault on the idea of the inheritance of acquired characters and vigorous debates between self-styled “neo-Darwinians” on the one hand and “neo-Lamarckians” on the other, and turn to the beginning of the twentieth century to consider yet another historical twist in which Lamarck’s name was part of the package. In the early years of the twentieth century, neo- Darwinians and neo-Lamarckians were not the only rival theorists in the effort to identify the mechanisms by which evolution takes place. Among the other theories in vogue at the time—and one that furthermore held special appeal for experimental biologists—was the “mutation theory” of Hugo de Vries (de Vries 1901; Allen 1975). As it happened, there was one single species that featured in de Vries’ theory that new species could arise in a single generation as the result of but a single large jump or mutation. This species was the evening primrose, a plant named Oenothera lamarckiana after the French biologist. Lamarck had called it Aenotherea grandflora when he described it in the 1790s, but the plant was renamed in Lamarck’s honor by N. C. Seringe in 1828 (see Davis 1912). The irony here is that a plant named after Lamarck ended up starring in a particular explanation of species change that could scarcely have been more un- Lamarckian. The abrupt, discrete, discontinuous muta- tions featured in de Vries’s theory bore no resemblance to the slow, virtually imperceptible, continuous changes of Lamarck’s evolutionary hypothesizing.
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The Extended Evolutionary Synthesis and the role of soft inheritance in evolution

The Extended Evolutionary Synthesis and the role of soft inheritance in evolution

Jablonka and Lamb [9], in their comprehensive case for soft inheritance, argue that there are four dimensions or sources of evolutionary change – genetic inheritance and then three sources of soft-inheritance: epigenetic, behavioural and symbolic inheritance systems. They regard soft inheritance as providing phenotypic tailoring during the lifetime development of an organism. This is a position we have some regard for and will return to below (§ 4.1 & 5). However, Jablonka and Lamb [9] do not provide any account of how these soft-inheritance systems are orchestrated in order to provide this service [46]. Nor do they directly discuss tailoring in terms of inclusive fitness. Indeed, all that is provided is much proximate detail. None the less, they claim [5,21] that soft inheritance systems play a Lamarckian role in the overall evolutionary dynamic such that epigenetic processes allow for the inheritance of acquired characteristics [15]. So, on the one hand epigenetic, behavioural and symbolic systems are seen as proximate mechanisms that provide a phenotypic tailoring service across the lifespan and on the other this very action introduces new variation into the phenotype, changing frequencies at the population level, being transmitted across generations and looking like evolutionary change. In doing this they have conflated proximate and ultimate causation.
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Mechanisms of Transgenerational Centromere Inheritance

Mechanisms of Transgenerational Centromere Inheritance

89 a similar mouse, that would overexpress tagged CENP-A specifically in the testis, would require engineering and validating expression of transgenes for minimally both exogenous CENP-A and HJURP. Since we had already generated Cenpa conditional knockout mice, as described in Chapter 3 (Smoak et al., 2016), it seemed feasible that by using commercially available mice expressing cre-recombinase under gonad specific promoters, we might be able to generate mice with a reduced amount of centromeric CENP-A. As discussed in previous chapters, in the absence of any nascent CENP-A protein, 50% of existing CENP-A protein is lost each cell cycle through dilution during S-phase (Jansen et al., 2007), eventually passing a threshold after which centromere function is impaired to disastrous effect (Black et al., 2007). Since spermatagonia proceed through some mitotic divisions prior to meiosis, this experimental approach exploits cell- cycle coupled CENP-A depletion through carefully timed deletion of Cenpa, with respect to spermatogenesis, to control the amount of CENP-A present in mature sperm. The timing of Cenpa excision is essential: if Cenpa is deleted too early, loss of CENP-A from centromeres prior to meiosis will likely cause meiotic arrest and/or cell death, with no mature sperm to use for experiments; if Cenpa is deleted too late, there will likely be no centromeric CENP-A loss. In the following sections, I will outline the rationale behind the available cre-drivers we selected, the preliminary results obtained from these experiments, and my thoughts on future directions to address interesting questions related to centromere inheritance through the male germline.
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Mechanisms and evolution of resistance to environmental extremes in animals

Mechanisms and evolution of resistance to environmental extremes in animals

several families of disparate IDPs from a broad range of organisms, including tardigrades, which have known or suspected links to stress tolerance [50–53]. Additionally, it is known that denatured globular proteins (essentially IDPs) vitrify upon desiccation, and that the addition of IDPs to trehalose strengthens the resulting glass [54, 55]. Could endogenously disordered proteins form glasses on their own? One study in tardigrades has linked the abil- ity of these animals to survive desiccation to the produc- tion of IDPs [44]. However, further experiments will be needed to confirm the widespread ability of IDPs to form glasses on their own. Despite what will be found in other organisms, the ability of tardigrades to use protein-based glasses to tolerate desiccation and high temperatures represents an elegant example of how evolution can con- verge on a similar mechanism (vitrification) via two dis- tinct mediators (a sugar versus a protein) [44].
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Skill learning and the evolution of social learning mechanisms

Skill learning and the evolution of social learning mechanisms

Developmental mechanisms are also an important con- sideration in the evolution of SE and OL. We implement SE and OL as tendencies that are fixed over a lifetime. However, animals could plausibly ‘learn to socially learn’ [55], including through domain-general mechanisms [54]. If such learning would be governed by immediate rewards, however, our analysis points to difficulties in how it would arise. To the extent that our model is realistic, it implies that the immediate direct effect of SE is a reduction in average rewards since foragers tend to become biased to resources for which they have low skill (Fig. 4d), while the direct effect of OL is a time cost and no reward. In principle, foragers could therefore learn to associate the choices of others with low rewards, in which case learn- ing to socially learn might be more challenging than it first appears, at least in a ‘skill learning’ context. Where this occurs, we would predict SE and OL to be underpinned by attentional or motivation biases, which, together with the aforementioned cognitive pre-requisites of OL, may be regarded as social learning adaptations. The question of whether the evolution of social learning requires the evo- lution of social-learning-specific adaptations remains one the major unresolved issues in the field, but it is likely that the answer will depend on the social learning mechanism involved.
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The evolution of slope failures: mechanisms of rupture propagation

The evolution of slope failures: mechanisms of rupture propagation

of sliding on existing surfaces, they suggested that an asymp- totic trend might be expected to be observed in 3 − t space. This is borne out by the work of Petley et al. (2002), who demonstrated that an asymptotic trend is indeed displayed in non-brittle landslide systems. Further, Petley and Petley (2004) demonstrated that for the massive, catastrophic Vajont landslide in 1963 two periods of acceleration prior to the fi- nal failure were not characterised by linearity, whilst the final failure did show a clear linear trend. This was taken to imply that the basal mechanisms evolved through time, changing from an essentially ductile process during the creeping phase to a brittle process at final failure. This concurs with the sug- gestions made on the basis of the deformation mechanics by Petley (1996) and Petley and Allison (1997).
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Generative Mechanisms for Digital Platform Ecosystem Evolution

Generative Mechanisms for Digital Platform Ecosystem Evolution

Early on, Danske Bank had decided to replicate its success with the rapid adoption of MobilePay in Denmark by offering the platform to other markets where the bank has significant market positions. As a result, they had entered the Finish market in late 2014 and the Norwegian market in 2015, but with limited success. In summer 2015, the owner sought to reinforce its Nordic ambition and protect itself from upcoming international payment platforms such as ApplePay and SamsungPay. To strengthen its market position in the region, the owner opened up MobilePay through a partnership model with other Nordic banks. Following prolonged negotiations, Nordea, a major Nordic bank, joined MobilePay in September 2016, which triggered a new stage in the evolution of the ecosystem. The inclusion of partner banks as distribution and financial partners transformed the actors. Apart from distributing MobilePay to their commercial customers, the partner banks also acted as financial partners, investing resources in the future development of the platform. As such, their role in the ecosystem differed significantly from previous distribution partners (e.g., PSPs for online payments). The incorporation of partner banks also changed the architecture significantly and complemented the earlier efforts to resolve accumulated governance issues. By plugging into the existing payment systems of partner banks, Danske Bank further modified the platform core to complete the migration from card-based infrastructure to account-to-account infrastructure. This required development of new boundary resources (APIs) that integrated the core with the partner banks’ systems. Rather than implementing a comprehensive governance regime, the owner introduced a minimum set of rules to avoid stalling the continued innovation of the platform. To access the platform and as an initial investment towards the development of MobilePay, partner banks paid an up-front fee. When partner banks invested further in MobilePay, Danske Bank rewarded their distribution efforts if they resulted in increased platform usage in terms of volume of transactions or growing number of commercial customers. Prioritizing speedy innovation, the platform owner restricted the participation of partner banks in the development of the platform. While Danske Bank created a dialogue with them to inquire about their innovation ideas, partner banks did not acquire any ownership over the platform despite their investments and as a result, had limited influence on MobilePay development.
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A representation of the configurations and evolution of metamorphic mechanisms

A representation of the configurations and evolution of metamorphic mechanisms

Research on the metamorphic mechanism has been mak- ing significant improvements in fundamentals and applica- tions for nearly twenty years. The essence and character- istics of metamorphic mechanisms as well as three meta- morphic approaches including variable components, adja- cent relations and kinematic joints were introduced by Dai et al. (2005a) and Liu and Yang (2004). In addition, some of the basic constituent elements of these mechanisms, including links and their connectivity relationships, remain unchanged to give the mechanism’s adjacent configuration complex cou- pling features. These two aspects are key factors affecting the study of methods for configuring metamorphic mechanisms
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Mechanisms of Chromosome Number Evolution in Yeast

Mechanisms of Chromosome Number Evolution in Yeast

Internal chromosomal positions differ from subtelomeric locations in terms of their chromatin configurations, which in turn affect the expression of nearby genes [70–72]. In general, subtelomeric regions tend to have higher nucleosome occupancy and silencing protein association, both of which generally reduce gene expression [70–72]. Subtelomeric genes are likely to be under less evolutionary constraint than genes in internal locations, are less essential and have higher variance in their expression profiles [73]. The rate of sequence evolution is negatively correlated with expression and essentiality, but positively correlated with the variance of gene expression [74–77]. Thus relocating a gene from telomeric to internal regions is likely to increase the evolutionary constraints on its sequence. Conversely, evolution may proceed at a faster pace at telomeres due to more relaxed selective constraints. If this higher evolutionary rate leads to an advantageous allele at a telomere, we hypothesize that it may be beneficial to relocate the gene to somewhere else in the genome where selection will maintain the advantageous allele under higher constraint. This could potentially constitute an ongoing cycle over evolutionary time, where the telomeres act as the cooking pots of evolution [78], with successful innovations moving to more stable regions.
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Mechanisms of change in the evolution of jargon aphasia

Mechanisms of change in the evolution of jargon aphasia

Well documented cases of the evolution of jargon aphasia are rare. Furthermore, recovery in this condition is not at all assured. For example, two of the four participants in Kohn et al (1996) showed no change over time. Clearly more longitudinal studies are needed to identify the patterns and predictors of change. Group studies, in particular, could identify prognosticators of recovery. In this context, some researchers have argued that perseveration is a negative marker (Kohn et al, 1996, Goldman, Schwartz & Wilshire, 2001). So it is interesting that TK improved despite making frequent perseverative errors. In Eaton et al (2010) we noted that TK rarely produced global or long distant perseverations. Therefore the type of perseveration may be an important factor. Further explorations of the associations and dissociations in recovery are also needed. For example, it may be that improved error awareness typically occurs hand in hand with production recovery, as was the case for TK. Alternatively, it may occur alone. Such evidence could throw more light on the nature of the monitoring impairment in jargon aphasia.
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The morphology of the Tasmantid Seamounts: interactions between tectonic inheritance and magmatic evolution

The morphology of the Tasmantid Seamounts: interactions between tectonic inheritance and magmatic evolution

To investigate if preexisting faults related to seafloor spreading may have impacted the morphology and structure of the Tasmantids, we map the orientations of the seamounts’ volcanic ridges and elongation axes (Figures 2 and 3, Comment S2, and Figures S2–S27). We also determine the extinct ridge structure of the Tas- man Sea (Comment S1 and Figure S1). We then group the seamounts according to tectonic setting (on fracture zone, on inside corner of ridge-transform intersections, etc.) and assess the consistency of trends to examine the importance of structural inheritance across the chain. Where seamounts span more than one category, we subdivide the mapped lineations according to local tectonic setting. For seamounts such as Mooloolaba or Stradbroke that span an entire short spreading segment, we divide the orientations into inside corner and outside corner domains for analysis, with no distinct midsegment stress regime due to the short segment length.
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Translation initiation: structures, mechanisms and evolution

Translation initiation: structures, mechanisms and evolution

The structures of eIF4E, bound to a cap analog, from yeast and mouse have been determined, as well as the complexes of eIF4E with small consensus peptides from 4E-BP and eIF4G (Marcotrigiano et al. 1997a, b ; Matsuo et al. 1997). The structure of eIF4E resembles a baseball glove, with the cap binding to the concave surface. Specific recognition of the 7-methyl-G of the cap is achieved by stacking between conserved tryptophan rings and direct contacts with the methyl group. N7-methylated guanosine nucleotides bind eIF4E with a 4- to 6-fold higher affinity than the non-methylated analogs. This can be attributed to an enhanced p–p-stacking interaction of the methylated base with the tryptophans. The methylation leads to electron deficient p-orbitals that interact favorably with the electron-rich p-orbitals of the tryptophan indols (Ishida et al. 1988 ; Carberry et al. 1990 ; Ueda et al. 1991). The consensus peptides bound to the dorsal surface of eIF4E. The consensus peptides, while sufficient for binding, did not account for all features of the eIF4E . 4E-BP and eIF4E . eIF4G interactions, such as the stabilization of eIF4E – cap binding by eIF4G (Haghighat & Sonenberg, 1997) or the role of 4E- BP phosphorylation for down-regulation of eIF4E binding (Haghighat et al. 1995). The structure of a complex between eIF4E and a y100 residue fragment of eIF4G was recently determined in our laboratory, providing new insights into the eIF4E . 4G and eIF4E . 4E-BP interactions (Gross et al. 2003) (Fig. 11). The eIF4G fragment was folded upon binding and wrapped around the N-terminus of eIF4E ; consistent with mutational and biochemical data (Hershey et al. 1999). The binding of the longer fragment was orders of magnitude more stable than that of the consensus peptide and caused stabilization of cap-binding by eIF4E. The tighter cap binding by eIF4E was not accompanied by significant structural changes in the cap-binding site, indicating that eIF4G binding indirectly stabilizes the cap-bound state of eIF4E. The observed larger
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Diversifying mechanisms in the on-farm evolution of crop mixtures

Diversifying mechanisms in the on-farm evolution of crop mixtures

Our findings highlight the remarkable ability of the mixture to respond to selection in drastic conditions. While we initially expected population differentiation to be mostly mediated through variation in the proportions of the mixture components, we found that within-compo- nent genetic evolution also substantially contributed. In particular, the TSB landrace, the most diversified land- race of the four, was identified as the keystone in the adaptation process of the mixture. This landrace was present in all populations, and it responded with differ- ent strategies for earliness depending on global environ- mental and agricultural conditions. These findings emphasize how critical it is to maintain within-variety genetic diversity. The distribution of crop genetic diver- sity met in on-farm management is a coproduct from the farmers’ self-organization. Therefore, this study shows that such social organization could potentially contribute to the adaptation of crop biodiversity to climate change. In addition, this short-term evolutionary experiment sets the stage for promising properties of mixtures and con- firms the potential of genetic diversity to maintain adapt- ability and stability in changing environments. This investigation needs to be continued on the medium term to confirm our results.
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Compliant space mechanisms: a new frontier for compliant mechanisms

Compliant space mechanisms: a new frontier for compliant mechanisms

design precision devices for specific tasks. The pseudo-rigid- body model (Howell, 2001) enables flexures to be modeled as rigid-link assemblies with representative link lengths and torsional spring constants. It also enables the use of well- known rigid-link kinematic and dynamic analysis software packages in analyzing compliant mechanisms. The advent of this approach has brought about many advances in numerous fields and lends itself particularly well to the space indus- try. Topology optimization (Sigmund, 1997; Frecker et al., 1997; Kim et al., 2006; Saxena and Ananthasuresh, 2000), another method of compliant mechanism design, can be used in the conceptual phase of design to arrive at the optimal ge- ometry for specific loading and boundary conditions. These and other tools, further discussed in Sect. 4.2, provide the
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THE INHERITANCE AND LINKAGE RELATIONS OF A NEW RECESSIVE SPOTTING IN THE HOUSE MOUSE

THE INHERITANCE AND LINKAGE RELATIONS OF A NEW RECESSIVE SPOTTING IN THE HOUSE MOUSE

If such is the case, the bellyspot non-flexed and flexed non-spot classes in tables 1 and 2 are not crossover classes but are merely overlaps which genotypically belong in th[r]

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CRIPPLED, A NEW MUTANT CHARACTER OF DROSOPHILA MELANOGASTER, AND ITS INHERITANCE

CRIPPLED, A NEW MUTANT CHARACTER OF DROSOPHILA MELANOGASTER, AND ITS INHERITANCE

When, on the other hand, the FI female was backcrossed, most of the crip-h flies of the next generation were also black purple cinnabar, but there appeared a few flie[r]

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MATHEMATICAL STUDY OF THE EVOLUTION OF GYNODIOECY WITH CYTOPLASMIC INHERITANCE UNDER THE EFFECT OF A NUCLEAR RESTORER GENE

MATHEMATICAL STUDY OF THE EVOLUTION OF GYNODIOECY WITH CYTOPLASMIC INHERITANCE UNDER THE EFFECT OF A NUCLEAR RESTORER GENE

Analytical study of equilibrium states and stability conditions: The results of the computer simulation showed that nuclear-cytoplasmic inheritance of g p - odioecy (situat[r]

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New Norfolk in evolution

New Norfolk in evolution

The village of :FaUs The rural population of New Norfolk, fairly dense in relation to that of Van Diemen's Land and New South Wales generally the average land grant to Norfolk Islanders [r]

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Mechanisms of Evolution in High Consequence Drug Resistance Plasmids

Mechanisms of Evolution in High Consequence Drug Resistance Plasmids

The plasmids identified at different time points in patients 15 and 16 appear to represent consecutive steps in plasmid evolution, as might be expected. We were somewhat surprised to find that when the plasmids among our two analyzed groups were exam- ined—isolated from different patients and the hospital environ- ment—there was little correlation between the date of isolate col- lection and location on the inferred evolutionary tree (Fig. 4H and 5G). As we believe we have unambiguously established the sequence of the plasmid transformation events, a reasonable explanation for such temporal incongruities is that the ancestors continue to coexist alongside the progeny resulting from the identified successive trans- positions within the larger population structure. It should be empha- sized that though our method establishes the sequence of events, it does not establish the location or timing of events, and we do not suggest that our analysis can establish whether the identified transfor- mations took place within the NIH Clinical Center; indeed this inter- pretation would be contradicted by epidemiologic evidence for many of the isolates (6, 7, 9). Rather, it is highly likely that our analysis
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