Biology subjects

Hatakeyama, T. S.

Publications and source records attributed to Hatakeyama, T. S..

5 recordsLinked to original sources

bioRxiv2022

Evolutionary Innovation by Polyploidy

The preferred conditions for evolutionary innovation is a fundamental question, but little is known, in part because the question involves rare events. We focused on the potential role of polyploidy in the evolution of novel traits. There are two hypotheses regarding the effects of polyploidy on evolution: Polyploidy reduces the effect of a single mutation and slows evolution. In contrast, the gene redundancy introduced by polyploidy will promote neofunctionalization and accelerate evolution. Does polyploidy speed up or slow down evolution? In this study, we proposed a simple model of polyploid cells and showed that the evolutionary rate of polyploids is similar to or much slower than that of haploids under neutral selection or during gradual evolution. However, on a fitness landscape where cells should jump over a lethal valley to increase their fitness, the probability of evolution in polyploidy could be drastically increased, and the optimal number of chromosomes was identified. We theoretically discussed the existence of this optimal chromosome numbers from the large deviation theory. Furthermore, we proposed that the optimization for achieving evolutionary innovation could determine the range of chromosome number in polyploid bacteria.

evolutionary biology↗

bioRxiv2022

Quantitative Relationship between Intracellular Metabolic Responses against Nutrient Conditions and Metabolic Inhibitions

Many previous studies have attempted to predict the metabolic states of cells assuming metabolic regulation is optimized through (sometimes artificial) evolution for some objective, e.g., growth rate or production of some metabolites. Conventional approaches, however, require identifying the microscopic details of individual metabolic reactions and the objective functions of cells, and their predictions sensitively depend on such details. In this study, we focus on the responses of metabolic systems to environmental perturbations, rather than their metabolic states themselves, and theoretically demonstrate a universal property of the responses independent of the systems details. With the help of a microeconomic theory, we show a simple relationship between intracellular metabolic responses against nutrient abundance and metabolic inhibition due to manipulation such as drug administration: these two experimentally measurable quantities show a proportional relationship with a negative coefficient. This quantitative relationship should hold in arbitrary metabolic systems as long as the law of mass conservation holds and cells are optimized for some objectives, but the true objective functions need not be known. Through numerical calculations using large-scale metabolic networks such as the E. coli core model, we confirmed that the relationship is valid from abstract to detailed models. Because the relationship provides quantitative predictions regarding metabolic responses without prior knowledge of systems, our findings have implications for experimental applications in microbiology, systems biology, metabolic engineering, and medicine, particularly for unexplored organisms or cells.

systems biology↗

bioRxiv2020

Autotoxin-mediated voluntary triage in starved yeast community

When organisms face crises, such as starvation, every individual should adapt to environmental changes (1, 2), or the community alters their behaviour (3-5). Because a stressful environment reduces the carrying capacity (6), the population size of unicellular organisms shrinks in such conditions (7, 8). However, the uniform stress response of the cell community may lead to overall extinction or severely damage their entire fitness. How microbial communities accommodate this dilemma remains poorly understood. Here, we demonstrate an elaborate strategy of the yeast community against glucose starvation, named the voluntary triage. During starvation, yeast cells release some autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the cells producing them. Although it may look like mass suicide at first glance, cells use epigenetic "tags" to adapt to the autotoxin inheritably. If non-tagged latecomers, regardless of whether they are closely related, try to invade the habitat, autotoxins kill them and inhibit their growth, but the tagged cells can selectively survive. Phylogenetically distant fission and budding yeast (9) share this strategy using the same autotoxins, which implies that the universal system of voluntary triage may be relevant to the major evolutional transition from unicellular to multicellular organisms (10).

microbiology↗

bioRxiv2020

Functional Sensitivity and Mutational Robustness of Proteins

Sensitivity and robustness appear to be contrasting concepts. However, natural proteins are robust enough to tolerate random mutations, meanwhile be susceptible enough to sense environmental signals, exhibiting both high functional sensitivity (i.e., plasticity) and mutational robustness. Uncovering how these two aspects are compatible is a fundamental question in the protein dynamics and genotype-phenotype relation. In this work, a general framework is established to analyze the dynamics of protein systems under both external and internal perturbations. We introduce fluctuation entropy for the functional sensitivity and the spectrum entropy for the mutational robustness. The compatibility of sensitivity and robustness is analyzed by the optimization of two entropies, which leads to the power-law vibration spectrum of proteins. These power-law behaviors are confirmed extensively by protein data, as a hallmark of criticality. Moreover, the dependence of functional sensitivity and mutational robustness on the protein size suggests a general evolutionary constraint for proteins with different chain lengths. This framework can also establish a general link of the criticality with robustness-plasticity compatibility, both of which are ubiquitous features in biological systems.

biophysics↗

bioRxiv2019

Microeconomics of metabolism: Overflow metabolism as Giffen behavior

Biological systems such as intracellular metabolism are rationally regulated to maximize the cellular growth rate through evolution (1-4), whereas microeconomics investigates the behaviour of consumers assumed to rationally maximize their utility (5, 6). Despite this analogy as optimization problems, the link between biology and economics has not been fully established (7, 8). Here, we developed an exact mapping between the regulation of metabolism and the theory of consumer choice, thereby revealing the correspondence between long-standing mysteries in both fields: overflow metabolism and Giffen behaviour. Overflow metabolism, particularly known as the Warburg effect in cancer (9, 10), is a seemingly wasteful but ubiquitous strategy where cells utilize aerobic glycolysis instead of the more energetically-efficient oxidative phosphorylation (9-16), whereas Giffen behaviour is the unexpected consumer behaviour where a good is demanded more as its price rises (17, 18). We revealed that the general conditions for these phenomena are trade-off and complementarity, i.e., impossibility of substitution for different goods. This correspondence implies that oxidative phosphorylation is counterintuitively stimulated when its efficiency is decreased by metabolic perturbations like drug administration. Therefore, Giffen behaviour bridges the Warburg effect and the reverse and inverse Warburg effect (19-22). This highlights that application of microeconomics to metabolism can offer new predictions and paradigms for both biology and economics.

systems biology↗