Natural selection defines the cellular complexity

2015 ◽  
Author(s):  
Han Chen ◽  
Xionglei He

Current biology is perplexed by the lack of a theoretical framework for understanding the organization principles of the molecular system within a cell. Here we first studied growth rate, one of the seemingly most complex cellular traits, using functional data of yeast single-gene deletion mutants. We observed nearly one thousand expression informative genes (EIGs) whose expression levels are linearly correlated to the trait within an unprecedentedly large functional space. A simple model considering six EIG-formed protein modules revealed a variety of novel mechanistic insights, and also explained ~50% of the variance of cell growth rates measured by Bar-seq technique for over 400 yeast mutants (Pearson's R = 0.69), a performance comparable to the microarray-based (R = 0.77) or colony-size-based (R = 0.66) experimental approach. We then applied the same strategy to 501 morphological traits of the yeast and achieved successes in most fitness-coupled traits each with hundreds of trait-specific EIGs. Surprisingly, there is no any EIG found for most fitness-uncoupled traits, indicating that they are controlled by super-complex epistases that allow no simple expression-trait correlation. Thus, EIGs are recruited exclusively by natural selection, which builds a rather simple functional architecture for fitness-coupled traits, and the endless complexity of a cell lies primarily in its fitness-uncoupled features.

2007 ◽  
Vol 28 (4) ◽  
pp. 1404-1412 ◽  
Author(s):  
Donghong Ju ◽  
Xiaogang Wang ◽  
Haiming Xu ◽  
Youming Xie

ABSTRACT The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the Rpn4 transcription factor upregulates the proteasome genes and is rapidly degraded by the proteasome. Previous work has identified Ubr2 and Rad6 as the cognate E3 and E2 enzymes for Rpn4 ubiquitylation. However, our recent attempts to ubiquitylate Rpn4 using purified Ubr2 and Rad6 proteins in a reconstitution system have been unsuccessful, suggesting that an additional factor is required for Rpn4 ubiquitylation. Here, we screened the entire collection of the single-gene-deletion yeast mutants generated by the Saccharomyces Genome Deletion Project and identified the mub1Δ mutant defective in ubiquitin-dependent degradation of Rpn4. An in vitro reconstitution ubiquitylation assay confirms that Mub1 is the missing factor for Rpn4 ubiquitylation. We further show that Mub1 directly interacts with Ubr2 and Rpn4. The MYND domain of Mub1 may play an important role in Rpn4 ubiquitylation. Interestingly, Mub1 itself is a short-lived protein and its degradation is dependent on the Ubr2/Rad6 ubiquitin ligase. Together, these data suggest that Mub1 and Ubr2 cooperate to transfer ubiquitin to Rpn4 from Rad6 and that Mub1 may switch from a partner to a substrate of the Ubr2/Rad6 ubiquitin ligase.


2021 ◽  
Author(s):  
QinQin Yu ◽  
Matti Gralka ◽  
Marie-Cécilia Duvernoy ◽  
Megan Sousa ◽  
Arbel Harpak ◽  
...  

AbstractDemographic noise, the change in the composition of a population due to random birth and death events, is an important driving force in evolution because it reduces the efficacy of natural selection. Demographic noise is typically thought to be set by the population size and the environment, but recent experiments with microbial range expansions have revealed substantial strain-level differences in demographic noise under the same growth conditions. Many genetic and phenotypic differences exist between strains; to what extent do single mutations change the strength of demographic noise? To investigate this question, we developed a high-throughput method for measuring demographic noise in colonies without the need for genetic manipulation. By applying this method to 191 randomly-selected single gene deletion strains from the E. coli Keio collection, we find that a typical single gene deletion mutation decreases demographic noise by 8% (maximal decrease: 81%). We find that the strength of demographic noise is an emergent trait at the population level that can be predicted by colony-level traits but not cell-level traits. The observed differences in demographic noise from single gene deletions can increase the establishment probability of beneficial mutations by almost an order of magnitude (compared to in the wild type). Our results show that single mutations can substantially alter adaptation through their effects on demographic noise and suggest that demographic noise can be an evolvable trait of a population.


2021 ◽  
Vol 30 (5) ◽  
pp. 497-520
Author(s):  
Zdravka Kostova ◽  

The article discusses successive stages in the evolution of life up to the establishment of the prokaryotic cell emphasizing the transitions from pre-biotic environment to organic precursors, pre-RNA-RNA, RNA-proteins-DNA, DNA-LUCA. They are paired with the development of pre-biotic structural progenitors of a cell - micelles, vesicles, protocells, prokaryotic ancestor, two prokaryotic branches – Eubacteria and Archaebacteria. The driving force is the natural selection (chemical, biochemical and biological), maintaining the correspondence between the emerging structures and their environment.


2005 ◽  
Vol 24 (4) ◽  
pp. 203-214 ◽  
Author(s):  
Chada S Reddy

The protein kinase C (PKC) family of proteins mediates the action of growth factors and other ligands by activating a network of transcription factors that bind to TRE sequences in the promoters of many genes that regulate cell proliferation, differentiation, extracellular matrix synthesis, apoptosis and others in a cell type-, isozymeand context-specific manner. The critical role of PKC in embryonic development is indicated by early death of embryos in which one or more of these isozymes are inactivated. Our studies together with others show that palatal PKC signalling is functional and may be essential for normal palate development. Although single gene knockouts have failed to exhibit the cleft palate (CP) phenotype, owing to compensation by other kinases, many chemicals including the mycotoxin, secalonic acid D, disrupt palatal PKC signalling leading to altered palatal mesenchymal gene expression. The potential relevance of such effects to chemical-induced CP is discussed.


2014 ◽  
Vol 11 (100) ◽  
pp. 20140706 ◽  
Author(s):  
Mithun K. Mitra ◽  
Paul R. Taylor ◽  
Chris J. Hutchison ◽  
T. C. B. McLeish ◽  
Buddhapriya Chakrabarti

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington's landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represent their undifferentiated and differentiated states, respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single-gene regulatory circuit. We show that the interplay of time-dependent drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.


2003 ◽  
Vol 3 ◽  
pp. 1359-1362 ◽  
Author(s):  
Xiang-Dong Gao ◽  
Stefan Albert

The efficient organization of the actin cytoskeleton is important for many cellular functions. However, how the local actin organization is regulated in a cell is not well understood. By using yeast mutants defective in actin organization and secretion, we demonstrated that exocytosis plays a role in the spatial regulation of actin organization. Our findings suggest that the actin cytoskeleton, exocytosis, and perhaps endocytosis, may depend on each other for efficiency and reinforce each other.


2015 ◽  
Vol 22 (5) ◽  
pp. 895-906 ◽  
Author(s):  
Mark A. McCormick ◽  
Joe R. Delaney ◽  
Mitsuhiro Tsuchiya ◽  
Scott Tsuchiyama ◽  
Anna Shemorry ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4136-4136
Author(s):  
Barbara J. Bryant ◽  
Julie A. Hopkins ◽  
Susan F. Leitman

Abstract Donors of apheresis blood components are routinely evaluated with a complete blood count (CBC) at the time of each donation. In otherwise healthy donors, recurrent low mean corpuscular volume (MCV) values (< 80 fL) in the presence of an acceptable hemoglobin (≥ 12.5 gm/dL) could be due to iron deficiency or to an hemoglobinopathy, such as alpha thalassemia trait or a beta chain variant trait. Iron deficiency in repeat blood donors may warrant treatment with oral iron supplementation, whereas donors with hemoglobinopathies in the absence of iron deficiency do not need treatment. Pre-donation samples for CBC (Cell-Dyn 4000, Abbott) were obtained from all apheresis donors donating platelets, plasma, granulocytes, lymphocytes, and monocytes. MCV values <80 fL were electronically flagged via a donor database module for review by medical staff. Donors with MCV ≤ 80 fL on two or more occasions were evaluated for iron deficiency and the presence of hemoglobinopathies. CBC, ferritin, serum iron, transferrin, percent transferrin saturation, and hemoglobin electrophoresis were performed at the time of a subsequent donation. Iron deficiency was defined as values below the reference range for ferritin or transferrin saturation. Alpha thalassemia trait was presumed if the red blood cell count was elevated, no variant hemoglobins were detected by electrophoresis, and the ferritin, percent transferrin saturation, serum iron, and transferrin levels were all within normal ranges. In a one-year period, 25 of 1333 healthy apheresis donors had a low MCV on more than one occasion. Donors with low MCV were more likely to be African American (AA) (12 of 25, 48%) or Asian (2 of 25, 8%) compared with donors without a low MCV (AA 193 of 1308, 15%; Asian 37 of 1308, 3%). Iron deficiency was present in 60% (15 of 25) of the low-MCV donors: 36% (9) had isolated iron deficiency, 20% (5) had iron deficiency with probable alpha thalassemia trait, and 4% (1) had hemoglobin C trait with coexistent iron deficiency. Hemoglobinopathy without concomitant iron deficiency was found in 40% (10 of 25) of the low-MCV donors and included 24% (6) with presumed alpha thalassemia trait, 4% (1) with hemoglobin S trait and single gene deletion alpha thalassemia trait (hemoglobin S concentration 34%), 4% (1) with hemoglobin S trait and double gene deletion alpha thalassemia trait (hemoglobin S concentration 28%), 4% (1) with hemoglobin Lepore trait, and 4% (1) with hemoglobin G-Philadelphia trait with at least a single gene deletion alpha thalassemia trait (hemoglobin G-Philadelphia concentration 36%). Although the combination of MCV, hemoglobin, and red cell count available from the routine CBC were often helpful in discriminating iron deficiency from hemoglobinopathy, the frequent coexistence of both processes resulted in a need for further laboratory evaluation, both before and after iron repletion, to confirm the diagnosis. In a sample of American repeat apheresis donors, iron deficiency is present in the majority with recurrent low MCV values and hemoglobin levels ≥ 12.5 gm/dL. Concurrent hemoglobinopathy is also commonly present but may not be easily recognized in the setting of iron deficiency. The MCV is a useful screening tool to detect iron deficiency in a repeat blood donor population, however low MCV values should be further investigated in the blood donor setting to determine if iron replacement therapy is indicated.


Yeast ◽  
2011 ◽  
Vol 28 (5) ◽  
pp. 349-361 ◽  
Author(s):  
Katsunori Yoshikawa ◽  
Tadamasa Tanaka ◽  
Yoshihiro Ida ◽  
Chikara Furusawa ◽  
Takashi Hirasawa ◽  
...  

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