Introduction

• Unicellular organisms have existed for billions of years and still thrive in the world today. However, some unicellular organisms started to form complex, multicellular structures.
• This paper investigates how multicellularity may have evolved as a response to environmental threats, particularly when environmental unpredictability is high.
• Multicellularity may have arisen when single-celled organisms surrounded themselves with “protective” cells, reducing exposure to harmful factors in the environment.
• In this paper, the transition to multicellularity is explained using the Free-Energy Principle (FEP), which emphasizes reducing unpredictability in the environment.

Key Concepts

• Somatic Multicellularity: A form of multicellularity where cells are divided into reproductive (germ) and non-reproductive (somatic) cells. Somatic cells serve to protect reproductive cells.
• Free-Energy Principle (FEP): This principle suggests that organisms evolve to minimize the “free energy” (or unpredictability) of their environment by adapting their behavior.
• Markov Blanket: A theoretical concept in which certain cells (the somatic cells) form a protective layer around the reproductive cells to shield them from environmental threats.
• Prediction Error Minimization: Cells and organisms aim to reduce the difference between what they expect from their environment and what actually happens, thereby reducing the risk of harm.

What Drives the Evolution of Multicellularity?

• In unicellular organisms, reproduction is the main goal, and cells replicate to increase their numbers.
• However, in environments with high risks (like predators or toxins), reproductive cells face dangers that could wipe them out before they have a chance to reproduce.
• The solution proposed in this paper is that some cells began to “sacrifice” their ability to reproduce, instead forming protective somatic cells that shielded the reproductive cells.
• These somatic cells reduced the environmental unpredictability (or variational free energy) for the reproductive cells, increasing the chance of survival.

The Transition to Somatic Multicellularity

• When environmental threats (e.g., predators, toxins) increase, cells must adapt to survive. One adaptation is to invest resources in building a protective environment for the reproductive cells.
• In this model, the transition to multicellularity occurs when reproductive cells stop dividing and instead produce non-reproductive somatic cells that provide environmental protection.
• This shift can be viewed as a “phase transition,” similar to a material going from a liquid to a solid state, but at the level of cellular behavior.
• The transition from unicellular organisms to multicellular ones is driven by the need to minimize “prediction error”—that is, reducing the uncertainty about environmental threats.

Modeling the Evolution of Multicellularity

• The authors use a simulation model to show how multicellular bodies can form when reproductive cells sacrifice some of their reproductive resources to create a protective somatic layer.
• The model involves a grid where stem cells (reproductive cells) are placed in various environmental conditions with different levels of lethality.
• As environmental lethality increases, the cells’ ability to reproduce decreases unless they invest in protecting themselves, leading to the formation of somatic cells.
• The model predicts that this “protection” becomes essential when environmental dangers exceed a certain threshold, resulting in the phase transition to multicellularity.

Somatic Cells as Protectors

• Somatic cells, which cannot reproduce, act as protectors for the reproductive cells by forming a physical barrier against environmental threats.
• These cells provide a stable environment, reducing the unpredictability and the risk of harm to the reproductive cells, allowing them to continue their role in reproduction.
• Through this protection, somatic cells increase the overall survival chances of the organism by focusing on environmental defense rather than reproduction.

The Role of Cancer in This Model

• The paper suggests that cancer can be understood as an escape from the control exerted by reproductive cells over somatic cells.
• When somatic cells “break free” from the rules that restrict their reproduction, they revert to a state where they begin dividing uncontrollably, similar to the behavior of reproductive cells.
• This rebellion from the protective somatic state leads to cancer, which can be viewed as a failure in the system that originally protected the reproductive cells.

The Nervous System and Its Role

• The nervous system is suggested to have evolved not only to control behavior but also to regulate the proliferation of somatic cells.
• As multicellular organisms became more complex, the nervous system took on the additional role of controlling the growth and differentiation of somatic cells to maintain the organism’s shape and function.
• This role of the nervous system aligns with the model that somatic cells act as information processors, regulating their own behavior and interactions to maintain homeostasis.

Key Conclusions

• The origin of multicellularity can be understood as an adaptive response to environmental unpredictability, where non-reproductive somatic cells protect the reproductive cells from threats.
• This model helps explain the evolution of complex multicellular organisms, suggesting that the nervous system may have played a crucial role in regulating somatic cell behavior.
• Cancer is viewed as an escape from the regulatory control of reproductive cells, highlighting the importance of control over cell division in multicellular organisms.
• The development of somatic multicellularity and its regulatory mechanisms forms the basis of the evolutionary transition to complex animal bodies.

观察到的内容

• 单细胞生物已经存在了数十亿年，并且至今仍在世界各地繁荣。然而，一些单细胞生物开始形成复杂的多细胞结构。
• 本文探讨了如何通过应对环境威胁来推动多细胞性进化，特别是在环境不确定性高时。
• 多细胞性可能是在单细胞生物围绕自己形成“保护性”细胞的情况下出现的，从而减少暴露于环境中的有害因素。
• 本文使用自由能原理（FEP）来解释多细胞性的转变，强调减少环境中的不确定性。

关键概念

• 体细胞多细胞性：一种多细胞性，其中细胞被分为繁殖（生殖）和非繁殖（体细胞）细胞。体细胞的作用是保护生殖细胞。
• 自由能原理（FEP）：该原理表明，生物体通过适应其行为来最小化环境的“自由能”（或不确定性）。
• 马尔可夫被膜：一种理论概念，其中某些细胞（体细胞）围绕生殖细胞形成保护层，保护它们免受环境威胁。
• 预测误差最小化：细胞和有机体旨在减少它们对环境的期望与实际发生之间的差异，从而减少伤害的风险。

多细胞性的进化驱动力是什么？

• 在单细胞生物中，繁殖是主要目标，细胞通过复制来增加数量。
• 然而，在有高风险的环境中（如捕食者或毒素），生殖细胞面临着危险，这些危险可能在它们有机会繁殖之前就将它们消灭。
• 本文提出的解决方案是，一些细胞开始“牺牲”它们的繁殖能力，转而形成提供保护的体细胞，这些细胞保护生殖细胞。
• 这些体细胞减少了生殖细胞的环境不确定性（或变异自由能），从而增加了生殖细胞的生存机会。

体细胞多细胞性的转变

• 当环境威胁（如捕食者、毒素）增加时，细胞必须适应才能生存。一个适应是将资源投入到为生殖细胞建立保护性环境中。
• 在这个模型中，转向多细胞性发生在生殖细胞停止分裂，并产生不能繁殖的体细胞，这些体细胞提供环境保护。
• 这种转变可以被看作是“相变”，类似于材料从液体到固体状态的变化，但发生在细胞行为的层面上。
• 从单细胞生物到多细胞生物的转变是由最小化“预测误差”的需求驱动的，即减少对环境威胁的不确定性。

模拟多细胞性进化的模型

• 作者使用一个模拟模型来展示，当生殖细胞将一些繁殖资源投入到创建保护性体细胞层时，多细胞体如何形成。
• 该模型涉及一个网格，在其中，干细胞（生殖细胞）被放置在具有不同致死水平的各种环境条件下。
• 随着环境致死性的增加，细胞的繁殖能力下降，除非它们投资于保护自己，从而导致体细胞的形成。
• 该模型预测，当环境危险超过某个临界点时，保护变得至关重要，从而导致向多细胞性转变的相变。

体细胞作为保护者

• 体细胞，不能繁殖，作为保护者为生殖细胞提供保护，形成物理屏障，抵御环境威胁。
• 这些细胞提供一个稳定的环境，减少不确定性和生殖细胞的伤害风险，使它们能够继续执行繁殖功能。
• 通过这种保护，体细胞通过集中在环境防御而非繁殖上，提高了有机体的整体生存机会。

癌症在此模型中的角色

• 本文建议，癌症可以被理解为体细胞摆脱生殖细胞控制的一种表现。
• 当体细胞“逃脱”了限制它们繁殖的规则时，它们就会恢复到一种不受控制的分裂状态，类似于生殖细胞的行为。
• 这种体细胞的反叛导致了癌症，可以被看作是原本保护生殖细胞系统的失败。

神经系统及其作用

• 神经系统被认为不仅控制行为，还调节体细胞的增殖。
• 随着多细胞有机体变得更加复杂，神经系统发挥了调节体细胞生长和分化的额外作用，以维持有机体的形状和功能。
• 这种作用与模型相符，其中体细胞被看作信息处理器，调节它们的行为和相互作用，以维持稳态。

关键结论

• 多细胞性的起源可以被理解为应对环境不确定性的适应性反应，其中非繁殖的体细胞保护生殖细胞免受威胁。
• 该模型有助于解释复杂多细胞有机体的进化，建议神经系统可能在调节体细胞行为方面发挥了关键作用。
• 癌症被视为体细胞摆脱生殖细胞控制的表现，强调了控制细胞分裂在多细胞有机体中的重要性。
• 体细胞多细胞性的发展及其调控机制构成了复杂动物体的进化基础。