Evolution, adaptaion, homeostasis, and the preprogrammed processes essential for life to survive in a changing environment

Evolution, adaptation, homeostasis, and the preprogrammed processes essential for life to survive in a changing environment 

https://reasonandscience.catsboard.com/t2724-evolution-adaptaion-homeostasis-and-the-essential-preprogrammed-processes-essential-for-life-to-survive-in-a-changing-environment

Microevolution is better described as adaptation and is an engineered process, which does not happen by accident. The Cell receives macroscopic signals from the environment and responds by adaptive, nonrandom mutations. The capacity of Mammals and other multicellular organisms to adapt to changing environmental conditions is extraordinary.  In order to effectively produce and secrete mature proteins, cellular mechanisms for monitoring the environment are essential. Exposure of cells to various environmental causes accumulation of unfolded proteins and results in the activation of a well-orchestrated set of pathways during a phenomenon known as the unfolded protein response (UPR). Cells have powerful quality control networks consisting of chaperones and proteases that cooperate to monitor the folding states of proteins and to remove misfolded conformers through either refolding or degradation. Free-living organisms, which are more directly exposed to environmental fluctuations, must often survive even harsher folding stresses. These stresses not only disrupt the folding of newly synthesized proteins but can also cause misfolding of already folded proteins.  In living organisms, robustness is provided by homeostatic mechanisms. At least five epigenetic mechanisms are responsible for these life-essential processes :

- heat shock factors (HSFs)
- The unfolded protein response (UPR)
- nonhomologous end-joining and homologous recombination
- The DNA Damage Response
- The Response to Oxidative Stress

The cell modulates the signalling pathways at transcriptional, post-transcriptional and post-translational levels. Complex signalling pathways contribute to the maintenance of systemic homeostasis. Homeostasis is the mechanistic fundament of living organisms. 

Homeostasis, from the Greek words for "same" and "steady," refers to any process that living things use to actively maintain fairly stable conditions necessary for survival. It is also synonymous with robustness and adaptability.

This essential characteristic of living cells, homeostasis, is the ability to maintain a steady and more-or-less constant chemical balance in a changing environment. Cell survival requires appropriate proportions of molecular oxygen and various antioxidants. Reactive products of oxygen, calles Reactive Oxygen Species ( ROS) are amongst the most potent and omnipresent threats faced by cells. Cells, damaged by ROS, irreversibly infected, functionless and/or potentially oncogenic cells are destined for persistent inactivation or elimination, respectively. If mechanisms that do not trigger controlled and programmed Cell death ( apoptosis) are not present at day 1, the organisms cannot survive and dies. Simply put, the principle is that all of a multicellular organism's cells are prepared to suicide when needed for the benefit of the organism as a whole. They eliminate themselves in a very carefully programmed way so as to minimize damage to the larger organism.  On average, in human adults, it’s about 50-70 BILLION cells that die per day. We shed 30,000 to 50,000 skin cells every minute.

1. The control of metabolism is a fundamental requirement for all life, with perturbations of metabolic homeostasis underpinning numerous disease-associated pathologies.
2. Any incomplete Metabolic network without the control mechanisms in place to get homeostasis would mean disease and cell death.
3. A minimal metabolic network and the control mechanisms had to be in place from the beginning, which means, and gradualistic explanation of the origin of biological Cells, and life is unrealistic. 
Life is an all or nothing business and points to a creative act of God.

Following  molecules must stay in a finely tuned order and balance for life to survive:
- Halogens like chlorine, fluoride, iodine, and bromine.  The body needs to maintain a delicate balance between all these elements.
- Molybdenum (Mo) and iron (Fe) are essential micronutrients required for crucial enzyme activities and mutually impact their homeostasis, which means, they are interdependent on each other to maintain homeostatic levels. 
- Potassium plays a key role in maintaining cell function, and it is important in maintaining fluid and electrolyte balance. Potassium-40 is probably the most dangerous light radioactive isotope, yet the one most essential to life. Its abundance must be balanced on a razor’s edge.
- The ability of cells to maintain a large gradient of calcium across their outer membrane is universal. All biological cells have a low cytosolic (liquid found inside Cells ) calcium concentration, can and must keep this even when the free calcium outside is up to 20,000 times higher concentrated! 
- Nutrient uptake and homeostasis must be adjusted to the needs of the organisms according to developmental stages and environmental conditions.
- Magnesium is the second most abundant cellular cation after potassium. The concentrations are essential to regulate numerous cellular functions and enzymes
- Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport 
- Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its homeostasis must be tightly regulated. 
- Zinc (Zn) is an essential heavy metal that is incorporated into a number of human Zn metalloproteins. Zn plays important roles in nucleic acid metabolism, cell replication, and tissue repair and growth. Zn contributes to intracellular metal homeostasis. 
- Selenium homeostasis and antioxidant selenoproteins in the brain: lack of finetuned balance has implications for disorders in the central nervous system
- Copper ion homeostasis is maintained through regulated expression of genes involved in copper ion uptake. 

In the early 1960s, Ernest Nagel and Carl Hempel showed that self-regulated systems are teleological.

In his book: THE TINKERER’S ACCOMPLICE, How Design Emerges from Life Itself  J . SCOTT. TURNER, writes at page 12 :
Although I touch upon ID obliquely from time to time, I do so not because I endorse it, but because it is mostly unavoidable. ID theory is essentially warmed-over natural theology, but there is, at its core, a serious point that deserves serious attention. ID theory would like us to believe that some overarching intelligence guides the evolutionary process: to say the least, that is unlikely. Nevertheless, how design arises remains a very real problem in biology.  My thesis is quite simple: organisms are designed not so much because natural selection of particular genes has made them that way, but because agents of homeostasis build them that way. These agents’ modus operandi is to construct environments upon which the precarious and dynamic stability that is homeostasis can be imposed, and design is the result.

Comment: The author does not identify these agents, but Wiki describes agents as CONSCIOUS beings, which act with specific goals in mind. In the case of life, this agent made it possible for biological cells to actively maintain fairly stable levels of various metabolites and molecules, necessary for survival. We are once more, upon careful examination of the evidence in nature, justified to infer an intelligent designer as most case-adequate explanation of the origin of homeostasis and the ability of adaptation, commonly called evolution, of all living organisms.




1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081528/
2. https://www.hindawi.com/journals/ijcb/2010/214074/
3. http://sci-hub.ren/https://www.nature.com/articles/s41580-018-0068-0
4. http://sci-hub.ren/https://www.ncbi.nlm.nih.gov/pubmed/26711677

Signaling pathways and regulators of PRRs. 
Pattern-recognition receptors (PRRs) share intracellular pathways that lead to the production of pro-inflammatory cytokines and type I interferons (IFNs). 
a | All the Toll-like receptors (TLRs), except for TLR3, interact with MYD88 to induce the activation of nuclear factor-κB (NF‑κB) and mitogen-activated protein kinases (MAPKs), which induce the transcription factor activator protein 1 (AP-1), for the induction of pro-inflammatory cytokine expression. The TIR domain-containing adaptor protein inducing IFNβ (TRIF) pathway is shared by TLR4 and TLR3, and induces the activation of interferon regulatory factors IRF3–IRF7 for the production of type I IFNs.
b | Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) first interact with mitochondrial antiviral signaling protein (MAVS) and then activate signaling cascades through stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1), leading to the expression of type I IFNs. MAVS also signals through receptor-interacting serine/threonine protein kinase 1 (RIPK1) for AP‑1 activation. 
c | Many cytosolic DNA and RNA sensors, including cyclic GMP–AMP synthase (cGAS), double-strand break repair protein MRE11, IFNγ-inducible protein 16 (IFI16), DNA-dependent protein kinase (DNA‑PK), the probable ATP-dependent RNA helicases DDX41 and DDX60, leucine-rich repeat flightless interacting protein 2 (LRRFIP2) and protein kinase RNA-activated (PKR), recognize intracellular DNA or RNA and converge on STING to drive type I IFNs and cytokine production. The ATP-dependent RNA helicases DHX9 and DHX36 recognize CpG-containing DNA and induce the MYD88‑dependent signalling pathway. 
d | NOD-like receptors (NLRs) are activated upon cellular infection or stress, and engage innate immune responses via RIPK2–NF‑κB signalling activation. Some NLRs, such as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), ICE protease-activating factor (IPAF) and NLR apoptosis inhibitory protein 5 (NAIP5), form inflammasomes that contain the apoptosis-associated speck-like protein containing a CARD (ASC) and caspase 1, and trigger the maturation of interleukin-1β (IL-1β). 4

"Proteostasis network,”


There is your vocab word for today. This is a colossal 1000 component system dedicated to proper folding of proteins, without which disease would be rampant. Imagine 1000 molecular machines working to sort out misfolded proteins, guide them to other hospital proteins "chaperones" all this too keep us alive. How did any of these helper proteins evolve? No one knows. How vital is this system? ABSOLUTE! GIVE GOD GLORY TODAY FOR THE PROTEOSTASIS NETWORK!

In his lab at MIT, Shoulders uses a variety of techniques to study the “proteostasis network,” which comprises about a thousand components that cooperate to enable cells to maintain proteins in the right conformations.

“Proteostasis is exceedingly important. If it breaks down, you get disease,” he says. “There’s this whole system in cells that helps client proteins get to the shapes they need to get to, and if folding fails the system responds to try and address the problem. If it can’t be solved, the network actively works to dispose of misfolded or aggregated client proteins.”

https://scitechdaily.com/mit-chemist-investigates-how-diseases-are-linked-to-flawed-protein-folding/?fbclid=IwAR0iHrmGKTAUS5vvzNV93c-sIMS12NBL0dm_3PHIvq4tyEuSwoqwE1pHcAY

A. N. Brooks (2012):   Microbes have unique strategies to deal with the peculiarities of their environment. Environmental adaptation of biological systems can be considered from three perspectives:

1. Acclimation of existing cellular machinery to operate optimally in a new environmental niche;
2. Acquisition of entirely new capabilities through horizontal gene transfer or neofunctionalization of gene duplications and
3. Reorganization of network dynamics to appropriately adjust existing physiological processes to match dynamic environmental changes.

The first type of adaptation can arise through two types of events that differ dramatically in duration. Simple mutations can greatly increase fitness over very short time frames (within one or few generations). Prominent examples of short-term adaptive events include resistance to drugs and altered nutrient conditions. Alternatively, complex mutations in multiple loci may accumulate over very long time frames, such as the evolution of acidic protein surfaces in halophilic archaea. While the initial transfer of adaptive genes by HGT occurs rapidly, full integration of laterally transferred component(s) typically occurs over longer time frames, where HGT events often require regulatory rewiring to function optimally in the context of existing cellular networks. Finally, physiological readjustment occurs both because of genetic and physiological robustness to withstand stress that accumulates over many generations and latent genetic variance that is revealed after environmental perturbation.

Organisms have adaptive mechanisms to acclimate to the environment. Transient changes permit selecting genetic traits that confer fitness by improving the ability of an organism to rapidly and reversibly adjust physiology to match current environmental conditions. These traits manifest at varying hierarchies of genetic information processing, from receptors for sensing environmental factors, to signal relay, transcriptional, post-transcriptional, translational and post-translational control mechanisms, and also at the metabolic level through modulation of enzyme function (affinities, kinetics etc.). Fitness, or the number of surviving offspring after one generation, is a complex property that emerges from the integration of changes at all these levels. A holistic systems approach, therefore, is necessary to fully appreciate how these varied mechanisms work together when an organism adapts to a new environment.

Comment: It becomes clear, that adaptation is not dependent only on genetic variations through mutations, but on the orchestration depending on complex integrated sophisticated mechanisms that work in an interdependent manner in a joint venture together, and as such, require a designed engineered implementation. They cannot be the result of successive, slow, step-wise built-up just by unguided evolutionary pressures.

Adaptation and physiological readjustment equips organisms to attune their physiology to dynamic changes in their environments. Principles of systems biology permit a more comprehensive, integrative understanding of cellular adaptation to new environments.

What is adaptation?

When we say that an organism has adapted to its habitat, we imply that it employs molecular mechanisms that allow it to grow optimally under the spatiotemporally varying physicochemical conditions of its environment. Organisms chase fitness optima in constantly changing environments. Subtle fitness differences between individuals (due to genomic plasticity or metabolic flexibility) and phylogenetic complexity (i.e. numbers and diversity of species within a community) can lead to the diversification of species or the extinction of less fit genotypes over time. Most organisms have robust generalized mechanisms to deal with shared aspects of stress resulting from diverse kinds of environmental changes. In yeast, for example, a set of ~900 genes responds similarly to a diverse array of environmental stresses, sharing common regulatory themes. This generalized stress response typically includes activation of heat shock proteins, phage shock proteins, and oxidative stress response proteins. 1

Cellular Stress Responses: Cell Survival and Cell Death

S.Fulda (2010): Cells respond to stress in a variety of ways ranging from activation of pathways that promote survival to eliciting programmed cell death that eliminates damaged cells. The cell’s initial response to a stressful stimulus is geared towards helping the cell to defend against and recover from the insult. However, if the noxious stimulus is unresolved, then cells activate death signaling pathways. The fact that the cell’s survival critically depends on the ability to mount an appropriate response towards environmental or intracellular stress stimuli can explain why this reaction is highly conserved. For example, antioxidant defence mechanisms against oxidative injury and stress proteins such as heat shock proteins occur in lower organisms as well as the mammals. There are many different types of stress and the response a cell mounts to deal with these conditions will depend on the type and level of the insult. For example, protective responses such as the heat shock response or the unfolded protein response mediate an increase in chaperone protein activity which enhances the protein folding capacity of the cell, thus counteracting the stress and promoting cell survival. The adaptive capacity of a cell ultimately determines its fate. Therefore, depending on the level and mode of stress, different defense mechanisms and prosurvival strategies are mounted; however, if these are unsuccessful, then the cell death programs are activated to eliminate these damaged cells from the organism. The mechanism by which a cell dies, that is, apoptosis, necrosis, pyroptosis, or autophagic cell death, often depends on its ability to cope with the conditions to which it is exposed. There are different forms of cell death that can be activated by adaptive responses because activation of death signaling pathways is the ultimate response to all types of persistent irresolvable stress.

Stress-Induced Cell Death
Cell death has many forms and shapes. Cell death research encompasses not only the study of programmed forms of cell death (both apoptosis and autophagic cell death), necrosis and other modes of cellular demise but also the role these phenomena play in physiological and pathological processes including development, aging, and disease.

The cell death field has attracted much attention in the last two decades, mainly because of its relevance to development, degenerative diseases, and cancer. The term programmed cell death refers to controlled or regulated forms of death associated with a series of biochemical and morphological changes. The realization that some forms of cell death were biologically controlled or programmed has led to exploitation of these processes. Nowadays, programmed cell death is synonymous with apoptosis; however, based on the original definition it also refers to autophagic cell death. The term apoptosis was first used to describe a particular morphology of cell death common to the vast majority of physiological cell deaths. This morphology includes shrinkage and blebbing of cells, rounding and fragmentation of nuclei with condensation, and margination of chromatin, shrinkage, and phagocytosis of cell fragments without accompanying inflammatory responses (in most cases). The morphology of cells undergoing apoptosis appeared dissimilar and distinct from the morphology associated with necrosis. Necrosis, a term commonly used by pathologists, refers to any deaths associated with the loss of control of ionic balance, uptake of water, swelling, and cellular lysis. This lysis releases many intracellular constituents, attracting immune cells and provoking an inflammatory response.

A. N. Brooks: Adaptation of cells to new environments  2010 Dec 31