Cell biology

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Cell_biology

Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and functioning of organisms. Cell biology is the study of the structural and functional units of cells. Cell biology encompasses both prokaryotic and eukaryotic cells and has many subtopics which may include the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition. The study of cells is performed using several microscopy techniques, cell culture, and cell fractionation. These have allowed for and are currently being used for discoveries and research pertaining to how cells function, ultimately giving insight into understanding larger organisms. Knowing the components of cells and how cells work is fundamental to all biological sciences while also being essential for research in biomedical fields such as cancer, and other diseases. Research in cell biology is interconnected to other fields such as genetics, molecular genetics, molecular biology, medical microbiology, immunology, and cytochemistry.

History

Cells were first seen in 17th-century Europe with the invention of the compound microscope. In 1665, Robert Hooke referred to the building blocks of all living organisms as "cells" (published in Micrographia) after looking at a piece of cork and observing a structure reminiscent of a monastic cell; however, the cells were dead. They gave no indication to the actual overall components of a cell. A few years later, in 1674, Anton Van Leeuwenhoek was the first to analyze live cells in his examination of algae. Many years later, in 1831, Robert Brown discovered the nucleus. All of this preceded the cell theory which states that all living things are made up of cells and that cells are organisms' functional and structural units. This was ultimately concluded by plant scientist Matthias Schleiden and animal scientist Theodor Schwann in 1838, who viewed live cells in plant and animal tissue, respectively. 19 years later, Rudolf Virchow further contributed to the cell theory, adding that all cells come from the division of pre-existing cells. Viruses are not considered in cell biology – they lack the characteristics of a living cell and instead are studied in the microbiology subclass of virology.

Techniques

Cell biology research looks at different ways to culture and manipulate cells outside of a living body to further research in human anatomy and physiology, and to derive medications. The techniques by which cells are studied have evolved. Due to advancements in microscopy, techniques and technology have allowed scientists to hold a better understanding of the structure and function of cells. Many techniques commonly used to study cell biology are listed below:

• Cell culture: Utilizes rapidly growing cells on media which allows for a large amount of a specific cell type and an efficient way to study cells. Cell culture is one of the major tools used in cellular and molecular biology, providing excellent model systems for studying the normal physiology and biochemistry of cells (e.g., metabolic studies, aging), the effects of drugs and toxic compounds on the cells, and mutagenesis and carcinogenesis. It is also used in drug screening and development, and large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins).
• Fluorescence microscopy: Fluorescent markers such as GFP, are used to label a specific component of the cell. Afterwards, a certain light wavelength is used to excite the fluorescent marker which can then be visualized.
• Phase-contrast microscopy: Uses the optical aspect of light to represent the solid, liquid, and gas-phase changes as brightness differences.
• Confocal microscopy: Combines fluorescence microscopy with imaging by focusing light and snap shooting instances to form a 3-D image.
• Transmission electron microscopy: Involves metal staining and the passing of electrons through the cells, which will be deflected upon interaction with metal. This ultimately forms an image of the components being studied.
• Cytometry: The cells are placed in the machine which uses a beam to scatter the cells based on different aspects and can therefore separate them based on size and content. Cells may also be tagged with GFP-fluorescence and can be separated that way as well.
• Cell fractionation: This process requires breaking up the cell using high temperature or sonification followed by centrifugation to separate the parts of the cell allowing for them to be studied separately.

Cell types

Main article: Cell types

A drawing of a prokaryotic cell

There are two fundamental classifications of cells: prokaryotic and eukaryotic. Prokaryotic cells are distinguished from eukaryotic cells by the absence of a cell nucleus or other membrane-bound organelle. Prokaryotic cells are much smaller than eukaryotic cells, making them the smallest form of life. Prokaryotic cells include Bacteria and Archaea, and lack an enclosed cell nucleus.  Eukaryotic cells are found in plants, animals, fungi, and protists. They range from 10 to 100 μm in diameter, and their DNA is contained within a membrane-bound nucleus. Eukaryotes are organisms containing eukaryotic cells. The four eukaryotic kingdoms are Animalia, Plantae, Fungi, and Protista.

They both reproduce through binary fission. Bacteria, the most prominent type, have several different shapes, although most are spherical or rod-shaped. Bacteria can be classed as either gram-positive or gram-negative depending on the cell wall composition. Gram-positive bacteria have a thicker peptidoglycan layer than gram-negative bacteria. Bacterial structural features include a flagellum that helps the cell to move, ribosomes for the translation of RNA to protein, and a nucleoid that holds all the genetic material in a circular structure. There are many processes that occur in prokaryotic cells that allow them to survive. In prokaryotes, mRNA synthesis is initiated at a promoter sequence on the DNA template comprising two consensus sequences that recruit RNA polymerase. The prokaryotic polymerase consists of a core enzyme of four protein subunits and a σ protein that assists only with initiation. For instance, in a process termed conjugation, the fertility factor allows the bacteria to possess a pilus which allows it to transmit DNA to another bacteria which lacks the F factor, permitting the transmittance of resistance allowing it to survive in certain environments.

Structure and function

Structure of eukaryotic cells

Main article: Eukaryote

A diagram of an animal cell

Eukaryotic cells are composed of the following organelles:

• Nucleus: The nucleus of the cell functions as the genome and genetic information storage for the cell, containing all the DNA organized in the form of chromosomes. It is surrounded by a nuclear envelope, which includes nuclear pores allowing for the transportation of proteins between the inside and outside of the nucleus. This is also the site for replication of DNA as well as transcription of DNA to RNA. Afterwards, the RNA is modified and transported out to the cytosol to be translated to protein.
• Nucleolus: This structure is within the nucleus, usually dense and spherical. It is the site of ribosomal RNA (rRNA) synthesis, which is needed for ribosomal assembly.
• Endoplasmic reticulum (ER): This functions to synthesize, store, and secrete proteins to the Golgi apparatus. Structurally, the endoplasmic reticulum is a network of membranes found throughout the cell and connected to the nucleus. The membranes are slightly different from cell to cell and a cell's function determines the size and structure of the ER.
• Mitochondria: Commonly known as the powerhouse of the cell is a double membrane bound cell organelle. This functions for the production of energy or ATP within the cell. Specifically, this is the place where the Krebs cycle or TCA cycle for the production of NADH and FADH occurs. Afterwards, these products are used within the electron transport chain (ETC) and oxidative phosphorylation for the final production of ATP.
• Golgi apparatus: This functions to further process, package, and secrete the proteins to their destination. The proteins contain a signal sequence that allows the Golgi apparatus to recognize and direct it to the correct place. Golgi apparatus also produce glycoproteins and glycolipids.
• Lysosome: The lysosome functions to degrade material brought in from the outside of the cell or old organelles. This contains many acid hydrolases, proteases, nucleases, and lipases, which break down the various molecules. Autophagy is the process of degradation through lysosomes which occurs when a vesicle buds off from the ER and engulfs the material, then, attaches and fuses with the lysosome to allow the material to be degraded.
• Ribosomes: Functions to translate RNA to protein. it serves as a site of protein synthesis.
• Cytoskeleton: Cytoskeleton is a structure that helps to maintain the shape and general organization of the cytoplasm. It anchors organelles within the cells and makes up the structure and stability of the cell. The cytoskeleton is composed of three principal types of protein filaments: actin filaments, intermediate filaments, and microtubules, which are held together and linked to subcellular organelles and the plasma membrane by a variety of accessory proteins.
• Cell membrane: The cell membrane can be described as a phospholipid bilayer and is also consisted of lipids and proteins. Because the inside of the bilayer is hydrophobic and in order for molecules to participate in reactions within the cell, they need to be able to cross this membrane layer to get into the cell via osmotic pressure, diffusion, concentration gradients, and membrane channels.
• Centrioles: Function to produce spindle fibers which are used to separate chromosomes during cell division.

Eukaryotic cells may also be composed of the following molecular components:

• Chromatin: This makes up chromosomes and is a mixture of DNA with various proteins.
• Cilia: They help to propel substances and can also be used for sensory purposes.

Cell metabolism

Cell metabolism is necessary for the production of energy for the cell and therefore its survival and includes many pathways and also sustaining the main cell organelles such as the nucleus, the mitochondria, the cell membrane etc. For cellular respiration, once glucose is available, glycolysis occurs within the cytosol of the cell to produce pyruvate. Pyruvate undergoes decarboxylation using the multi-enzyme complex to form acetyl coA which can readily be used in the TCA cycle to produce NADH and FADH₂. These products are involved in the electron transport chain to ultimately form a proton gradient across the inner mitochondrial membrane. This gradient can then drive the production of ATP and H₂O during oxidative phosphorylation. Metabolism in plant cells includes photosynthesis which is simply the exact opposite of respiration as it ultimately produces molecules of glucose.

Cell signaling

Further information: Cell signaling

Cell signaling or cell communication is important for cell regulation and for cells to process information from the environment and respond accordingly. Signaling can occur through direct cell contact or endocrine, paracrine, and autocrine signaling. Direct cell-cell contact is when a receptor on a cell binds a molecule that is attached to the membrane of another cell. Endocrine signaling occurs through molecules secreted into the bloodstream. Paracrine signaling uses molecules diffusing between two cells to communicate. Autocrine is a cell sending a signal to itself by secreting a molecule that binds to a receptor on its surface. Forms of communication can be through:

• Ion channels: Can be of different types such as voltage or ligand gated ion channels. They allow for the outflow and inflow of molecules and ions.
• G-protein coupled receptor (GPCR): Is widely recognized to contain seven transmembrane domains. The ligand binds on the extracellular domain and once the ligand binds, this signals a guanine exchange factor to convert GDP to GTP and activate the G-α subunit. G-α can target other proteins such as adenyl cyclase or phospholipase C, which ultimately produce secondary messengers such as cAMP, Ip3, DAG, and calcium. These secondary messengers function to amplify signals and can target ion channels or other enzymes. One example for amplification of a signal is cAMP binding to and activating PKA by removing the regulatory subunits and releasing the catalytic subunit. The catalytic subunit has a nuclear localization sequence which prompts it to go into the nucleus and phosphorylate other proteins to either repress or activate gene activity.
• Receptor tyrosine kinases: Bind growth factors, further promoting the tyrosine on the intracellular portion of the protein to cross phosphorylate. The phosphorylated tyrosine becomes a landing pad for proteins containing an SH2 domain allowing for the activation of Ras and the involvement of the MAP kinase pathway.

Growth and development

Eukaryotic cell cycle

Main article: Cell cycle

The process of cell division in the animal cell cycle

Cells are the foundation of all organisms and are the fundamental units of life. The growth and development of cells are essential for the maintenance of the host and survival of the organism. For this process, the cell goes through the steps of the cell cycle and development which involves cell growth, DNA replication, cell division, regeneration, and cell death.

The cell cycle is divided into four distinct phases: G1, S, G2, and M. The G phase – which is the cell growth phase – makes up approximately 95% of the cycle. The proliferation of cells is instigated by progenitors. All cells start out in an identical form and can essentially become any type of cells. Cell signaling such as induction can influence nearby cells to determinate the type of cell it will become. Moreover, this allows cells of the same type to aggregate and form tissues, then organs, and ultimately systems. The G1, G2, and S phase (DNA replication, damage and repair) are considered to be the interphase portion of the cycle, while the M phase (mitosis) is the cell division portion of the cycle. Mitosis is composed of many stages which include, prophase, metaphase, anaphase, telophase, and cytokinesis, respectively. The ultimate result of mitosis is the formation of two identical daughter cells.

The cell cycle is regulated in cell cycle checkpoints, by a series of signaling factors and complexes such as cyclins, cyclin-dependent kinase, and p53. When the cell has completed its growth process and if it is found to be damaged or altered, it undergoes cell death, either by apoptosis or necrosis, to eliminate the threat it can cause to the organism's survival.

Cell mortality, cell lineage immortality

The ancestry of each present day cell presumably traces back, in an unbroken lineage for over 3 billion years to the origin of life. It is not actually cells that are immortal but multi-generational cell lineages. The immortality of a cell lineage depends on the maintenance of cell division potential. This potential may be lost in any particular lineage because of cell damage, terminal differentiation as occurs in nerve cells, or programmed cell death (apoptosis) during development. Maintenance of cell division potential over successive generations depends on the avoidance and the accurate repair of cellular damage, particularly DNA damage. In sexual organisms, continuity of the germline depends on the effectiveness of processes for avoiding DNA damage and repairing those DNA damages that do occur. Sexual processes in eukaryotes, as well as in prokaryotes, provide an opportunity for effective repair of DNA damages in the germ line by homologous recombination.

Cell cycle phases

The cell cycle is a four-stage process that a cell goes through as it develops and divides. It includes Gap 1 (G1), synthesis (S), Gap 2 (G2), and mitosis (M). The cell either restarts the cycle from G1 or leaves the cycle through G0 after completing the cycle. The cell can progress from G0 through terminal differentiation. Finally, the interphase refers to the phases of the cell cycle that occur between one mitosis and the next, and includes G1, S, and G2. Thus, the phases are:

• G1 phase: the cell grows in size and its contents are replicated.
• S phase: the cell replicates each of the 46 chromosomes.
• G2 phase: in preparation for cell division, new organelles and proteins form.
• M phase: cytokinesis occurs, resulting in two identical daughter cells.
• G0 phase: the two cells enter a resting stage where they do their job without actively preparing to divide.

Pathology

Main article: Cytopathology

The scientific branch that studies and diagnoses diseases on the cellular level is called cytopathology. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to the pathology branch of histopathology, which studies whole tissues. Cytopathology is commonly used to investigate diseases involving a wide range of body sites, often to aid in the diagnosis of cancer but also in the diagnosis of some infectious diseases and other inflammatory conditions. For example, a common application of cytopathology is the Pap smear, a screening test used to detect cervical cancer, and precancerous cervical lesions that may lead to cervical cancer.

Cell cycle checkpoints and DNA damage repair system

The cell cycle is composed of a number of well-ordered, consecutive stages that result in cellular division. The fact that cells do not begin the next stage until the last one is finished, is a significant element of cell cycle regulation. Cell cycle checkpoints are characteristics that constitute an excellent monitoring strategy for accurate cell cycle and divisions. Cdks, associated cyclin counterparts, protein kinases, and phosphatases regulate cell growth and division from one stage to another. The cell cycle is controlled by the temporal activation of Cdks, which is governed by cyclin partner interaction, phosphorylation by particular protein kinases, and de-phosphorylation by Cdc25 family phosphatases. In response to DNA damage, a cell's DNA repair reaction is a cascade of signaling pathways that leads to checkpoint engagement, regulates, the repairing mechanism in DNA, cell cycle alterations, and apoptosis. Numerous biochemical structures, as well as processes that detect damage in DNA, are ATM and ATR, which induce the DNA repair checkpoints.

The cell cycle is a sequence of activities in which cell organelles are duplicated and subsequently separated into daughter cells with precision. There are major events that happen during a cell cycle. The processes that happen in the cell cycle include cell development, replication and segregation of chromosomes.  The cell cycle checkpoints are surveillance systems that keep track of the cell cycle's integrity, accuracy, and chronology. Each checkpoint serves as an alternative cell cycle endpoint, wherein the cell's parameters are examined and only when desirable characteristics are fulfilled does the cell cycle advance through the distinct steps. The cell cycle's goal is to precisely copy each organism's DNA and afterwards equally split the cell and its components between the two new cells. Four main stages occur in the eukaryotes. In G1, the cell is usually active and continues to grow rapidly, while in G2, the cell growth continues while protein molecules become ready for separation. These are not dormant times; they are when cells gain mass, integrate growth factor receptors, establish a replicated genome, and prepare for chromosome segregation. DNA replication is restricted to a separate Synthesis in eukaryotes, which is also known as the S-phase. During mitosis, which is also known as the M-phase, the segregation of the chromosomes occur. DNA, like every other molecule, is capable of undergoing a wide range of chemical reactions. Modifications in DNA's sequence, on the other hand, have a considerably bigger impact than modifications in other cellular constituents like RNAs or proteins because DNA acts as a permanent copy of the cell genome. When erroneous nucleotides are incorporated during DNA replication, mutations can occur. The majority of DNA damage is fixed by removing the defective bases and then re-synthesizing the excised area. On the other hand, some DNA lesions can be mended by reversing the damage, which may be a more effective method of coping with common types of DNA damage. Only a few forms of DNA damage are mended in this fashion, including pyrimidine dimers caused by ultraviolet (UV) light changed by the insertion of methyl or ethyl groups at the purine ring's O6 position.

Mitochondrial membrane dynamics

Mitochondria are commonly referred to as the cell's "powerhouses" because of their capacity to effectively produce ATP which is essential to maintain cellular homeostasis and metabolism. Moreover, researchers have gained a better knowledge of mitochondria's significance in cell biology because of the discovery of cell signaling pathways by mitochondria which are crucial platforms for cell function regulation such as apoptosis. Its physiological adaptability is strongly linked to the cell mitochondrial channel's ongoing reconfiguration through a range of mechanisms known as mitochondrial membrane dynamics, including endomembrane fusion and fragmentation (separation) and ultrastructural membrane remodeling. As a result, mitochondrial dynamics regulate and frequently choreograph not only metabolic but also complicated cell signaling processes such as cell pluripotent stem cells, proliferation, maturation, aging, and mortality. Mutually, post-translational alterations of mitochondrial apparatus and the development of transmembrane contact sites among mitochondria and other structures, which both have the potential to link signals from diverse routes that affect mitochondrial membrane dynamics substantially, Mitochondria are wrapped by two membranes: an inner mitochondrial membrane (IMM) and an outer mitochondrial membrane (OMM), each with a distinctive function and structure, which parallels their dual role as cellular powerhouses and signaling organelles. The inner mitochondrial membrane divides the mitochondrial lumen into two parts: the inner border membrane, which runs parallel to the OMM, and the cristae, which are deeply twisted, multinucleated invaginations that give room for surface area enlargement and house the mitochondrial respiration apparatus. The outer mitochondrial membrane, on the other hand, is soft and permeable. It, therefore, acts as a foundation for cell signaling pathways to congregate, be deciphered, and be transported into mitochondria. Furthermore, the OMM connects to other cellular organelles, such as the endoplasmic reticulum (ER), lysosomes, endosomes, and the plasma membrane. Mitochondria play a wide range of roles in cell biology, which is reflected in their morphological diversity. Ever since the beginning of the mitochondrial study, it has been well documented that mitochondria can have a variety of forms, with both their general and ultra-structural morphology varying greatly among cells, during the cell cycle, and in response to metabolic or cellular cues. Mitochondria can exist as independent organelles or as part of larger systems; they can also be unequally distributed in the cytosol through regulated mitochondrial transport and placement to meet the cell's localized energy requirements. Mitochondrial dynamics refers to the adaptive and variable aspect of mitochondria, including their shape and subcellular distribution.

Autophagy

Main article: Autophagy

Autophagy is a self-degradative mechanism that regulates energy sources during growth and reaction to dietary stress. Autophagy also cleans up after itself, clearing aggregated proteins, cleaning damaged structures including mitochondria and endoplasmic reticulum and eradicating intracellular infections. Additionally, autophagy has antiviral and antibacterial roles within the cell, and it is involved at the beginning of distinctive and adaptive immune responses to viral and bacterial contamination. Some viruses include virulence proteins that prevent autophagy, while others utilize autophagy elements for intracellular development or cellular splitting. Macro autophagy, micro autophagy, and chaperon-mediated autophagy are the three basic types of autophagy. When macro autophagy is triggered, an exclusion membrane incorporates a section of the cytoplasm, generating the autophagosome, a distinctive double-membraned organelle. The autophagosome then joins the lysosome to create an autolysosome, with lysosomal enzymes degrading the components. In micro autophagy, the lysosome or vacuole engulfs a piece of the cytoplasm by invaginating or protruding the lysosomal membrane to enclose the cytosol or organelles. The chaperone-mediated autophagy (CMA) protein quality assurance by digesting oxidized and altered proteins under stressful circumstances and supplying amino acids through protein denaturation. Autophagy is the primary intrinsic degradative system for peptides, fats, carbohydrates, and other cellular structures. In both physiologic and stressful situations, this cellular progression is vital for upholding the correct cellular balance. Autophagy instability leads to a variety of illness symptoms, including inflammation, biochemical disturbances, aging, and neurodegenerative, due to its involvement in controlling cell integrity. The modification of the autophagy-lysosomal networks is a typical hallmark of many neurological and muscular illnesses. As a result, autophagy has been identified as a potential strategy for the prevention and treatment of various disorders. Many of these disorders are prevented or improved by consuming polyphenol in the meal. As a result, natural compounds with the ability to modify the autophagy mechanism are seen as a potential therapeutic option. The creation of the double membrane (phagophore), which would be known as nucleation, is the first step in macro-autophagy. The phagophore approach indicates dysregulated polypeptides or defective organelles that come from the cell membrane, Golgi apparatus, endoplasmic reticulum, and mitochondria. With the conclusion of the autophagocyte, the phagophore's enlargement comes to an end. The auto-phagosome combines with the lysosomal vesicles to formulate an auto-lysosome that degrades the encapsulated substances, referred to as phagocytosis.

Carbon-based life

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Carbon-based_life

The Lewis structure of a carbon atom, showing its four valence electrons

Carbon is a primary component of all known life on Earth, and represents approximately 45–50% of all dry biomass. Carbon compounds occur naturally in great abundance on Earth. Complex biological molecules consist of carbon atoms bonded with other elements, especially oxygen and hydrogen and frequently also nitrogen, phosphorus, and sulfur (collectively known as CHNOPS).

Because it is lightweight and relatively small in size, carbon molecules are easy for enzymes to manipulate. Carbonic anhydrase is part of this process. Carbon has an atomic number of 6 on the periodic table. The carbon cycle is a biogeochemical cycle that is important in maintaining life on Earth over a long time span. The cycle includes carbon sequestration and carbon sinks. Plate tectonics are needed for life over a long time span, and carbon-based life is important in the plate tectonics process. Iron- and sulfur-based Anoxygenic photosynthesis life forms that lived from 3.80 to 3.85 billion years ago on Earth produced an abundance of black shale deposits. These shale deposits increase heat flow and crust buoyancy, especially on the sea floor, helping to increase plate tectonics. Talc is another organic mineral that helps drive plate tectonics. Inorganic processes also help drive plate tectonics. Carbon-based photosynthesis life caused a rise in oxygen on Earth. This increase of oxygen helped plate tectonics form the first continents. It is frequently assumed in astrobiology that if life exists elsewhere in the Universe, it will also be carbon-based. Critics, like Carl Sagan in 1973, refer to this assumption as carbon chauvinism.

Characteristics

Carbon is capable of forming a vast number of compounds, more than any other element, with almost ten million compounds described to date, and yet that is but a fraction of the number of compounds that are theoretically possible under standard conditions. The enormous diversity of carbon compounds, known as organic compounds, has led to a distinction between them and the inorganic compounds that do not contain carbon. The branch of chemistry that studies organic compounds is known as organic chemistry.

Carbon is the 15th most abundant element in the Earth's crust, and the fourth most abundant element in the universe by mass, after hydrogen, helium, and oxygen. Carbon's widespread abundance, its ability to form stable bonds with numerous other elements, and its unusual ability to form polymers at the temperatures commonly encountered on Earth enables it to serve as a common element of all known living organisms. In a 2018 study, carbon was found to compose approximately 550 billion tons of all life on Earth. It is the second most abundant element in the human body by mass (about 18.5%) after oxygen.

The most important characteristics of carbon as a basis for the chemistry of cellular life are that each carbon atom is capable of forming up to four valence bonds with other atoms simultaneously, and that the energy required to make or break a bond with a carbon atom is at an appropriate level for building large and complex molecules which may be both stable and reactive. Carbon atoms bond readily to other carbon atoms; this allows the building of arbitrarily long macromolecules and polymers in a process known as catenation. "What we normally think of as 'life' is based on chains of carbon atoms, with a few other atoms, such as nitrogen or phosphorus", per Stephen Hawking in a 2008 lecture, "carbon [...] has the richest chemistry."

Norman Horowitz was the head of the Jet Propulsion Laboratory's bioscience section for the first U.S. mission, Viking Lander of 1976, to successfully land an unmanned probe on the surface of Mars. He considered that the great versatility of the carbon atom makes it the element most likely to provide solutions, even exotic solutions, to the problems of survival on other planets. However, the results of this mission indicated that Mars was presently extremely hostile to carbon-based life. He also considered that, in general, there was only a remote possibility that non-carbon life forms would be able to evolve with genetic information systems capable of self-replication and adaptation.

Key molecules

The most notable classes of biological macromolecules used in the fundamental processes of living organisms include:

• Proteins, which are the building blocks from which the structures of living organisms are constructed (this includes almost all enzymes, which catalyse organic chemical reactions).
• Amino acid, make up proteins, included the use in genetic code of life.
• Nucleic acids, which carry genetic information.
• Ribonucleic acid (RNA), production of proteins.
• Deoxyribonucleic acid (DNA), nucleic acid in genetic form.
• Peptide, building block of proteins.
• Lipids, which also store energy, but in a more concentrated form, and which may be stored for extended periods in the bodies of animals.
• Phospholipid used in cell membrane.
• Carbohydrates, which store energy in a form that can be used by living cells.
• Lectin, for binding proteins.
• Monosaccharide, simple sugars, including glucose and fructose.
• Disaccharides, sugar soluble in water, including lactose, maltose, and sucrose.
• Starch, made of amylose and amylopectin, plants energy storage.
• Glycogen, energy in animals.
• Cellulose, a biopolymer, found in the cell walls of plants.
• Fatty acid, two types, saturated fat and unsaturated fat (oil), are stored energy.
• Essential fatty acid, needed but not synthesized by the human body.
• Steroid, hormone, and used in cell membrane.
• Neurotransmitter, are signaling molecules.
• Cholesterol, used in the brain and spinal cord of animals.
• Wax, found in beeswax and lanolin. Plant wax used for protection.
  

Main articles: Water, Photosynthesis, Geochemistry of carbon, and Cell (biology)

Schematic of photosynthesis in plants. The carbohydrates produced are stored in or used by the plant. Photosynthesis is foundation of food on Earth

Liquid water is essential for carbon-based life. Chemical bonding of carbon molecules requires liquid water. Water has the chemical property to make compound-solvent pairing. Water provides the reversible hydration of carbon dioxide. Hydration of carbon dioxide is needed in carbon-based life. All life on Earth uses the same biochemistry of carbon. Water is important in life's carbonic anhydrase the interaction of between carbon dioxide and water. Carbonic anhydrase needs a family of carbon base enzymes for the hydration of carbon dioxide and acid–base homeostasis, that regulates PH levels in life.  In plant life, liquid water is needed for photosynthesis, the biological process plants use to convert light energy and carbon dioxide into chemical energy. Water makes up 55% to 60% of the human body by weight.

Other candidates

Main article: Hypothetical types of biochemistry

A few other elements have been proposed as candidates for supporting biological systems and processes as fundamentally as carbon does, for example, processes such as metabolism. The most frequently suggested alternative is silicon. Silicon, atomic number of 14, more than twice the size of carbon, shares a group in the periodic table with carbon, can also form four valence bonds, and also bonds to itself readily, though generally in the form of crystal lattices rather than long chains. Despite these similarities, silicon is considerably more electropositive than carbon, and silicon compounds do not readily recombine into different permutations in a manner that would plausibly support lifelike processes. Silicon is abundant on Earth, but as it is more electropositive and in a water based environment it forms Si–O bonds rather than Si–Si bonds. Boron does not react with acids and does not form chains naturally. Thus boron is not a candidate for life. Arsenic is toxic to life, and its possible candidacy has been rejected. In the past (1960s-1970s) other candidates for life were plausible, but with time and more research, only carbon has the complexity and stability to make large molecules and polymers essential for life.

Fiction

Speculations about the chemical structure and properties of hypothetical non-carbon-based life have been a recurring theme in science fiction. Silicon is often used as a substitute for carbon in fictional lifeforms because of its chemical similarities. In cinematic and literary science fiction, when man-made machines cross from non-living to living, this new form is often presented as an example of non-carbon-based life. Since the advent of the microprocessor in the late 1960s, such machines are often classed as "silicon-based life". Other examples of fictional "silicon-based life" can be seen in the 1967 episode "The Devil in the Dark" from Star Trek: The Original Series, in which a living rock creature's biochemistry is based on silicon. 1994 The X-Files episode "Firewalker", in which a silicon-based organism is discovered in a volcano.

In the 1984 film adaptation of Arthur C. Clarke's 1982 novel 2010: Odyssey Two, a character argues, "Whether we are based on carbon or on silicon makes no fundamental difference; we should each be treated with appropriate respect."

In JoJolion, the eighth part of the larger JoJo's Bizarre Adventure series, a mysterious race of silicon-based lifeforms "Rock Humans" serve as the primary antagonists.

Evolution of the brain

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Evolution_of_the_brain 

Evolution of the brain from ape to man

The evolution of the brain refers to the progressive development and complexity of neural structures over millions of years, resulting in the diverse range of brain sizes and functions observed across different species today, particularly in vertebrates.

The evolution of the brain has exhibited diverging adaptations within taxonomic classes, such as Mammalia, and even more diverse adaptations across other taxonomic classes. Brain-to-body size scales allometrically. This means that as body size changes, so do other physiological, anatomical, and biochemical connections between the brain and body. Small-bodied mammals tend to have relatively large brains compared to their bodies, while larger mammals (such as whales) have smaller brain-to-body ratios. When brain weight is plotted against body weight for primates, the regression line of the sample points can indicate the brain power of a species. For example, lemurs fall below this line, suggesting that for a primate of their size, a larger brain would be expected. In contrast, humans lie well above this line, indicating they are more encephalized than lemurs and, in fact, more encephalized than any other primate. This suggests that human brains have undergone a larger evolutionary increase in complexity relative to size. Some of these changes have been linked to multiple genetic factors, including proteins and other organelles.

Early history

Main article: Evolution of nervous systems

Unsolved problem in biology:  How and why did the brain evolve?

One approach to understanding overall brain evolution is to use a paleoarchaeological timeline to trace the necessity for ever increasing complexity in structures that allow for chemical and electrical signaling. Because brains and other soft tissues do not fossilize as readily as mineralized tissues, scientists often look to other structures as evidence in the fossil record to get an understanding of brain evolution. This, however, leads to a dilemma as the emergence of organisms with more complex nervous systems with protective bone or other protective tissues that can then readily fossilize occur in the fossil record before evidence for chemical and electrical signaling. Evidence from 2008 showed that the ability to transmit electrical and chemical signals existed even before more complex multicellular lifeforms.

Fossilization of brain tissue, as well as other soft tissue, is nonetheless possible, and scientists can infer that the first brain structure appeared at least 521 million years ago, with fossil brain tissue present in sites of exceptional preservation.

Another approach to understanding brain evolution is to look at extant organisms that do not possess complex nervous systems, comparing anatomical features that allow for chemical or electrical messaging. For example, choanoflagellates are organisms that possess various membrane channels that are crucial to electrical signaling. The membrane channels of choanoflagellates' are homologous to the ones found in animal cells, and this is supported by the evolutionary connection between early choanoflagellates and the ancestors of animals. Another example of extant organisms with the capacity to transmit electrical signals would be the glass sponge, a multicellular organism, which is capable of propagating electrical impulses without the presence of a nervous system.

Before the evolutionary development of the brain, nerve nets, the simplest form of a nervous system developed. These nerve nets were a sort of precursor for the more evolutionarily advanced brains. They were first observed in Cnidaria and consist of a number of neurons spread apart that allow the organism to respond to physical contact. They are able to rudimentarily detect food and other chemicals, but these nerve nets do not allow them to detect the source of the stimulus.

Ctenophores also demonstrate this crude precursor to a brain or centralized nervous system, however they phylogenetically diverged before the phylum Porifera (the Sponges) and Cnidaria. There are two current theories on the emergence of nerve nets. One theory is that nerve nets may have developed independently in Ctenophores and Cnidarians. The other theory states that a common ancestor may have developed nerve nets, but they were lost in Porifera. While comparing the average neuron size and the packing density the difference between primate and mammal brains is shown.

A trend in brain evolution according to a study done with mice, chickens, monkeys and apes concluded that more evolved species tend to preserve the structures responsible for basic behaviors. A long term human study comparing the human brain to the primitive brain found that the modern human brain contains the primitive hindbrain region – what most neuroscientists call the protoreptilian brain. The purpose of this part of the brain is to sustain fundamental homeostatic functions, which are self regulating processes organisms use to help their bodies adapt. The pons and medulla are major structures found there. A new region of the brain developed in mammals about 250 million years after the appearance of the hindbrain. This region is known as the paleomammalian brain, the major parts of which are the hippocampi and amygdalas, often referred to as the limbic system. The limbic system deals with more complex functions including emotional, sexual and fighting behaviors. Of course, animals that are not vertebrates also have brains, and their brains have undergone separate evolutionary histories.

The brainstem and limbic system are largely based on nuclei, which are essentially balled-up clusters of tightly packed neurons and the axon fibers that connect them to each other, as well as to neurons in other locations. The other two major brain areas (the cerebrum and cerebellum) are based on a cortical architecture. At the outer periphery of the cortex, the neurons are arranged into layers (the number of which vary according to species and function) a few millimeters thick. There are axons that travel between the layers, but the majority of axon mass is below the neurons themselves. Since cortical neurons and most of their axon fiber tracts do not have to compete for space, cortical structures can scale more easily than nuclear ones. A key feature of cortex is that because it scales with surface area, more of it can be fit inside a skull by introducing convolutions, in much the same way that a dinner napkin can be stuffed into a glass by wadding it up. The degree of convolution is generally greater in species with more complex behavior, which benefits from the increased surface area.

The cerebellum, or "little brain," is behind the brainstem and below the occipital lobe of the cerebrum in humans. Its purposes include the coordination of fine sensorimotor tasks, and it may be involved in some cognitive functions, such as language and different motor skills that may involve hands and feet. The cerebellum helps keep equilibrium. Damage to the cerebellum would result in all physical roles in life to be affected. Human cerebellar cortex is finely convoluted, much more so than cerebral cortex. Its interior axon fiber tracts are called the arbor vitae, or Tree of Life.

The area of the brain with the greatest amount of recent evolutionary change is called the neocortex. In reptiles and fish, this area is called the pallium and is smaller and simpler relative to body mass than what is found in mammals. According to research, the cerebrum first developed about 200 million years ago. It is responsible for higher cognitive functions—for example, language, thinking, and related forms of information processing. It is also responsible for processing sensory input (together with the thalamus, a part of the limbic system that acts as an information router). The thalamus receives the different sensations before the information is then passed onto the cerebral cortex. Most of its function is subconscious, that is, not available for inspection or intervention by the conscious mind. The neocortex is an elaboration, or outgrowth, of structures in the limbic system, with which it is tightly integrated. The neocortex is the main part controlling many brain functions as it covers half of the whole brain in volume. The development of these recent evolutionary changes in the neocortex likely occurred as a result of new neural network formations and positive selections of certain genetic components.

Role of embryology

Further information: Embryology and Brain development timelines

In addition to studying the fossil record, evolutionary history can be investigated via embryology. An embryo is an unborn/unhatched animal and evolutionary history can be studied by observing how processes in embryonic development are conserved (or not conserved) across species. Similarities between different species may indicate evolutionary connection. One way anthropologists study evolutionary connection between species is by observing orthologs. An ortholog is defined as two or more homologous genes between species that are evolutionarily related by linear descent. By using embryology the evolution of the brain can be tracked between various species.

Bone morphogenetic protein (BMP), a growth factor that plays a significant role in embryonic neural development, is highly conserved amongst vertebrates, as is sonic hedgehog (SHH), a morphogen that inhibits BMP to allow neural crest development. Tracking these growth factors with the use of embryology provides a deeper understanding of what areas of the brain diverged in their evolution. Varying levels of these growth factors lead to differing embryonic neural development which then in turn affects the complexity of future neural systems. Studying the brain's development at various embryonic stages across differing species provides additional insight into what evolutionary changes may have historically occurred. This then allows scientists to look into what factors may have caused such changes, such as links to neural network diversity, growth factor production, protein- coding selections, and other genetic factors.

Randomizing access and increasing size

Some animal phyla have gone through major brain enlargement through evolution (e.g. vertebrates and cephalopods both contain many lineages in which brains have grown through evolution) but most animal groups are composed only of species with extremely small brains. Some scientists argue that this difference is due to vertebrate and cephalopod neurons having evolved ways of communicating that overcome the scalability problem of neural networks while most animal groups have not. They argue that the reason why traditional neural networks fail to improve their function when they scale up is because filtering based on previously known probabilities cause self-fulfilling prophecy-like biases that create false statistical evidence giving a completely false worldview and that randomized access can overcome this problem and allow brains to be scaled up to more discriminating conditioned reflexes at larger brains that lead to new worldview forming abilities at certain thresholds. This means when neurons scale in a non randomized fashion that their functionality becomes more limited due to their neural networks being unable to process more complex systems without the exposure to new formations. This is explained by randomization allowing the entire brain to eventually get access to all information over the course of many shifts even though instant privileged access is physically impossible. They cite that vertebrate neurons transmit virus-like capsules containing RNA that are sometimes read in the neuron to which it is transmitted and sometimes passed further on unread which creates randomized access, and that cephalopod neurons make different proteins from the same gene which suggests another mechanism for randomization of concentrated information in neurons, both making it evolutionarily worth scaling up brains.

Brain re-organization

With the use of in vivo Magnetic resonance imaging (MRI) and tissue sampling, different cortical samples from members of each hominoid species were analyzed. In each species, specific areas were either relatively enlarged or shrunken, which can detail neural organizations. Different sizes in the cortical areas can show specific adaptations, functional specializations and evolutionary events that were changes in how the hominoid brain is organized. In early prediction it was thought that the frontal lobe, a large part of the brain that is generally devoted to behavior and social interaction, predicted the differences in behavior between hominoid and humans. Discrediting this theory was evidence supporting that damage to the frontal lobe in both humans and hominoids show atypical social and emotional behavior; thus, this similarity means that the frontal lobe was not very likely to be selected for reorganization. Instead, it is now believed that evolution occurred in other parts of the brain that are strictly associated with certain behaviors. The reorganization that took place is thought to have been more organizational than volumetric; whereas the brain volumes were relatively the same but specific landmark position of surface anatomical features, for example, the lunate sulcus suggest that the brains had been through a neurological reorganization. There is also evidence that the early hominin lineage also underwent a quiescent period, or a period of dormancy, which supports the idea of neural reorganization.

Dental fossil records for early humans and hominins show that immature hominins, including australopithecines and members of Homo, have a quiescent period (Bown et al. 1987). A quiescent period is a period in which there are no dental eruptions of adult teeth; at this time the child becomes more accustomed to social structure, and development of culture. During this time the child is given an extra advantage over other hominoids, devoting several years into developing speech and learning to cooperate within a community. This period is also discussed in relation to encephalization. It was discovered that chimpanzees do not have this neutral dental period, which suggests that a quiescent period occurred in very early hominin evolution. Using the models for neurological reorganization it can be suggested the cause for this period, dubbed middle childhood, is most likely for enhanced foraging abilities in varying seasonal environments.

Genetic factors in recent evolution

Genes involved in the neuro-development and in neuron physiology are extremely conserved between mammalian species (94% of genes expressed in common between humans and chimpanzees, 75% between humans and mice), compared to other organs. Therefore, few genes account for species differences in the human brain development and function.

Development of the human cerebral cortex

Main differences rely on the evolution of non-coding genomic regions, involved in the regulation of gene expression. This leads to differential expression of genes during the development of the human brain compared to other species, including chimpanzees. Some of these regions evolved fast in the human genome (human accelerated regions). The new genes expressed during human neurogenesis are notably associated with the NOTCH, WNT and mTOR pathways, but are also involved ZEB2, PDGFD and its receptor PDGFRβ. The human cerebral cortex is also characterized by a higher gradient of retinoic acid in the prefrontal cortex, leading to higher prefrontal cortex volume. All these differential gene expression lead to higher proliferation of the neural progenitors leading to more neurons in the human cerebral cortex. Some genes are lost in their expression during the development of the human cerebral cortex like GADD45G and FLRT2/FLRT3.

Another source of molecular novelty rely on new genes in the human or hominid genomes through segmental duplication. Around 30 new genes in the hominid genomes are dynamically expressed during human corticogenesis. Some were linked to higher proliferation of neural progenitors: NOTCH2NLA/B/C, ARHGAP11B, CROCCP2, TBC1D3, TMEM14B. Patients with deletions with NOTCH2NL genes display microcephaly, showing the necessity of such duplicated genes, acquired in the human genomes, in the proper corticogenesis.

MCPH1 and ASPM

Bruce Lahn, the senior author at the Howard Hughes Medical Center at the University of Chicago and colleagues have suggested that there are specific genes that control the size of the human brain. These genes continue to play a role in brain evolution, implying that the brain is continuing to evolve. The study began with the researchers assessing 214 genes that are involved in brain development. These genes were obtained from humans, macaques, rats and mice. Lahn and the other researchers noted points in the DNA sequences that caused protein alterations. These DNA changes were then scaled to the evolutionary time that it took for those changes to occur. The data showed the genes in the human brain evolved much faster than those of the other species. Once this genomic evidence was acquired, Lahn and his team decided to find the specific gene or genes that allowed for or even controlled this rapid evolution. Two genes were found to control the size of the human brain as it develops. These genes are Microcephalin (MCPH1) and Abnormal Spindle-like Microcephaly (ASPM). The researchers at the University of Chicago were able to determine that under the pressures of selection, both of these genes showed significant DNA sequence changes. Lahn's earlier studies displayed that Microcephalin experienced rapid evolution along the primate lineage which eventually led to the emergence of Homo sapiens. After the emergence of humans, Microcephalin seems to have shown a slower evolution rate. On the contrary, ASPM showed its most rapid evolution in the later years of human evolution once the divergence between chimpanzees and humans had already occurred.

Each of the gene sequences went through specific changes that led to the evolution of humans from ancestral relatives. In order to determine these alterations, Lahn and his colleagues used DNA sequences from multiple primates then compared and contrasted the sequences with those of humans. Following this step, the researchers statistically analyzed the key differences between the primate and human DNA to come to the conclusion, that the differences were due to natural selection. The changes in DNA sequences of these genes accumulated to bring about a competitive advantage and higher fitness that humans possess in relation to other primates. This comparative advantage is coupled with a larger brain size which ultimately allows the human mind to have a higher cognitive awareness.

ZEB2 protein

ZEB2

ZEB2 is a protein- coding gene in the Homo sapien species. A 2021 study found that a delayed change in the shape of early brain cells causes the distinctly large human forebrain compared to other apes and identify ZEB2 as a genetic regulator of it, whose manipulation lead to acquisition of nonhuman ape cortical architecture in brain organoids.

NOVA1

In 2021, researchers reported that brain organoids created with stem cells into which they reintroduced the archaic gene variant NOVA1 present in Neanderthals and Denisovans via CRISPR-Cas9 shows that it has a major impact on neurodevelopment and that such genetic mutations during the evolution of the human brain underlie traits that separate modern humans from extinct Homo species. They found that expression of the archaic NOVA1 in cortical organoids leads to "modified synaptic protein interactions, affects glutamatergic signaling, underlies differences in neuronal connectivity, and promotes higher heterogeneity of neurons regarding their electrophysiological profiles". This research suggests positive selection of the modern NOVA1 gene, which may have promoted the randomization of neural scaling. A subsequent study failed to replicate the differences in organoid morphology between the modern human and the archaic NOVA1 variant, consistent with suspected unwanted side effects of CRISPR editing in the original study.

SRGAP2C and neuronal maturation

Less is known about neuronal maturation. Synaptic gene and protein expression are protracted, in line with the protracted synaptic maturation of human cortical neurons so called neoteny. This probably relies on the evolution of non-coding genomic regions. The consequence of the neoteny could be an extension of the period of synaptic plasticity and therefore of learning. A human-specific duplicated gene, SRGAP2C accounts for this synaptic neoteny and acts by regulating molecular pathways linked to neurodevelopmental disorders. Other genes are deferentially expressed in human neurons during their development such as osteocrin or cerebelin-2 .

LRRC37B and neuronal electrical properties

Even less is known about molecular specificities linked to the physiology of the human neurons. Human neurons are more divergent in the genes they express compared to chimpanzees than chimpanzees to gorilla, which suggests an acceleration of non-coding genomic regions associated with genes involved in neuronal physiology, in particular linked to the synapses. A hominid-specific duplicated gene, LRRC37B, codes for a transmembrane receptor that is selectively localized at the axon initial segment of human cortical pyramidal neurons. It inhibits their voltage-gated sodium channels that generate the action potentials leading to a lower neuronal excitability. Human cortical pyramidal neurons display a lower excitability compared to other mammalian species (including macaques and marmosets) which could lead to different circuit functions in the human species. Therefore, LRRC37B whose expression has been acquired in the human lineage after the separation from the chimpanzees could be a key gene in the function of the human cerebral cortex. LRRC37B binds to secreted FGF13A and SCN1B and modulate indirectly the activity of SCN8A, all involved in neural disorders such as epilepsy and autism. Therefore, LRRC37B may contribute to human-specific sensitivities to such disorders, both involved defects in neuronal excitability.

Genome repair

The genomic DNA of postmitotic neurons ordinarily does not replicate. Protection strategies have evolved to ensure the distinctive longevity of the neuronal genome. Human neurons are reliant on DNA repair processes to maintain function during an individual's life-time. DNA repair tends to occur preferentially at evolutionarily conserved sites that are specifically involved with the regulation of expression of genes essential for neuronal identity and function.

Other factors

Many other genetics may also be involved in recent evolution of the brain.

• For instance, scientists showed experimentally, with brain organoids grown from stem cells, how differences between humans and chimpanzees are also substantially caused by non-coding DNA (often discarded as relatively meaningless "junk DNA") – in particular via CRE-regulated expression of the ZNF558 gene for a transcription factor that regulates the SPATA18 gene. SPATA18 gene encodes a protein and is able to influence lysosome-like organelles that are found within mitochondria that eradicate oxidized mitochondrial proteins. This helps monitor the quality of the mitochondria as the disregulation of its quality control has been linked to cancer and degenerative diseases. This example may contribute to illustrations of the complexity and scope of relatively recent evolution to Homo sapiens.
• A change in gene TKTL1 could be a key factor of recent brain evolution and difference of modern humans to (other) apes and Neanderthals, related to neocortex-neurogenesis. However, the "archaic" allele attributed to Neanderthals is present in 0.03% of Homo sapiens, but no resultant phenotypic differences have been reported in these people. Additionally, as Herai et al. contend, more is not always better. In fact, enhanced neuron production "can lead to an abnormally enlarged cortex and layer-specific imbalances in glia/neuron ratios and neuronal subpopulations during neurodevelopment." Even the original study's authors agree that “any attempt to discuss prefrontal cortex and cognitive advantage of modern humans over Neandertals based on TKTL1 alone is problematic”.
• Some of the prior study's authors reported a similar ARHGAP11B mutation in 2016.
• Epigenetics also play a major role in the brain evolution in and to humans.

Recently evolved traits

Language

A genome-wide association study meta-analysis reported genetic factors of, the so far uniquely human, language-related capacities, in particular factors of differences in skill-levels of five tested traits. It e.g. identified association with neuroanatomy of a language-related brain area via neuroimaging correlation. The data contributes to identifying or understanding the biological basis of this recently evolved characteristic capability.

Human brain evolution

Further information: Cranial capacity and Brain-to-body mass ratio

One of the prominent ways of tracking the evolution of the human brain is through direct evidence in the form of fossils. The evolutionary history of the human brain shows primarily a gradually bigger brain relative to body size during the evolutionary path from early primates to hominids and finally to Homo sapiens. Because fossilized brain tissue is rare, a more reliable approach is to observe anatomical characteristics of the skull that offer insight into brain characteristics. One such method is to observe the endocranial cast (also referred to as endocasts). Endocasts occur when, during the fossilization process, the brain deteriorates away, leaving a space that is filled by surrounding sedimentary material over time. These casts, give an imprint of the lining of the brain cavity, which allows a visualization of what was there. This approach, however, is limited in regard to what information can be gathered. Information gleaned from endocasts is primarily limited to the size of the brain (cranial capacity or endocranial volume), prominent sulci and gyri, and size of dominant lobes or regions of the brain. While endocasts are extremely helpful in revealing superficial brain anatomy, they cannot reveal brain structure, particularly of deeper brain areas. By determining scaling metrics of cranial capacity as it relates to total number of neurons present in primates, it is also possible to estimate the number of neurons through fossil evidence.

Facial reconstruction of a Homo georgicus from over 1.5 Mya

Despite the limitations to endocasts, they can and do provide a basis for understanding human brain evolution, which shows primarily a gradually bigger brain. The evolutionary history of the human brain shows primarily a gradually bigger brain relative to body size during the evolutionary path from early primates to hominins and finally to Homo sapiens. This trend that has led to the present day human brain size indicates that there has been a 2-3 factor increase in size over the past 3 million years. This can be visualized with current data on hominin evolution, starting with Australopithecus, a group of hominins from which humans are likely descended. After all of the data, all observations concluded that the main development that occurred during evolution was the increase of brain size.

However, recent research has called into question the hypothesis of a threefold increase in brain size when comparing Homo sapiens with Australopithecus and chimpanzees. For example, in an article published in 2022 compiled a large data set of contemporary humans and found that the smallest human brains are less than twice that of large brained chimpanzees. As the authors write '...the upper limit of chimpanzee brain size is 500g/ml yet numerous modern humans have brain size below 900 g/ml.' (Note that in this quote, the unit g/ml is to be understood not in the usual way as gram per millilitre but rather as gram or millilitre. This is consistent because brain density is close to 1 g/ml.) Consequently, the authors argue that the notion of an increase in brain size being related to advances in cognition needs to be re-thought in light of global variation in brain size, as the brains of many modern humans with normal cognitive capacities are only 400g/ml larger than chimpanzees. Additionally, much of the increase in brain size - which occurs to a much greater degree in specific modern populations - can be explained by increases in correlated body size related to diet and climatic factors.

Australopiths lived from 3.85 to 2.95 million years ago with the general cranial capacity somewhere near that of the extant chimpanzee—around 300–500 cm³. Considering that the volume of the modern human brain is around 1,352 cm³ on average this represents a substantial amount of brain mass evolved. Australopiths are estimated to have a total neuron count of ~30-35 billion.

Progressing along the human ancestral timeline, brain size continues to steadily increase (see Homininae) when moving into the era of Homo. For example, Homo habilis, living 2.4 million to 1.4 million years ago and argued to be the first Homo species based on a host of characteristics, had a cranial capacity of around 600 cm³. Homo habilis is estimated to have had ~40 billion neurons.

A little closer to present day, Homo heidelbergensis lived from around 700,000 to 200,000 years ago and had a cranial capacity of around 1290 cm³ and having around 76 billion neurons.

Homo neaderthalensis, living 400,000 to 40,000 years ago, had a cranial capacity comparable to that of modern humans at around 1500–1600 cm³on average, with some specimens of Neanderthal having even greater cranial capacity. Neanderthals are estimated to have had around 85 billion neurons. The increase in brain size topped with Neanderthals, possibly due to their larger visual systems.

It is also important to note that the measure of brain mass or volume, seen as cranial capacity, or even relative brain size, which is brain mass that is expressed as a percentage of body mass, are not a measure of intelligence, use, or function of regions of the brain. Total neurons, however, also do not indicate a higher ranking in cognitive abilities. Elephants have a higher number of total neurons (257 billion) compared to humans (100 billion). Relative brain size, overall mass, and total number of neurons are only a few metrics that help scientists follow the evolutionary trend of increased brain to body ratio through the hominin phylogeny.

In 2021, scientists suggested that the brains of early Homo from Africa and Dmanisi, Georgia, Western Asia "retained a great ape-like structure of the frontal lobe" for far longer than previously thought – until about 1.5 million years ago. Their findings imply that Homo first dispersed out of Africa before human brains evolved to roughly their modern anatomical structure in terms of the location and organization of individual brain regions. It also suggests that this evolution occurred – not during – but only long after the Homo lineage evolved ~2.5 million years ago and after they – Homo erectus in particular – evolved to walk upright. What is the least controversial is that the brain expansion started about 2.6 Ma (about the same as the start of the Pleistocene), and ended around 0.2 Ma.

Evolution of the neocortex

Further information: Neocortex

In addition to just the size of the brain, scientists have observed changes in the folding of the brain, as well as in the thickness of the cortex. The more convoluted the surface of the brain is, the greater the surface area of the cortex which allows for an expansion of cortex. It is the most evolutionarily advanced part of the brain. Greater surface area of the brain is linked to higher intelligence as is the thicker cortex but there is an inverse relationship—the thicker the cortex, the more difficult it is for it to fold. In adult humans, thicker cerebral cortex has been linked to higher intelligence.

The neocortex is the most advanced and most evolutionarily young part of the human brain. It is six layers thick and is only present in mammals. It is especially prominent in humans and is the location of most higher level functioning and cognitive ability. The six-layered neocortex found in mammals is evolutionarily derived from a three-layer cortex present in all modern reptiles. This three-layer cortex is still conserved in some parts of the human brain such as the hippocampus and is believed to have evolved in mammals to the neocortex during the transition between the Triassic and Jurassic periods. After looking at history, the mammals had little neocortex compared to the primates as they had more cortex. The three layers of this reptilian cortex correlate strongly to the first, fifth and sixth layers of the mammalian neocortex. Across species of mammals, primates have greater neuronal density compared to rodents of similar brain mass and this may account for increased intelligence.

Theories of human brain evolution

Explanations of the rapid evolution and exceptional size of the human brain can be classified into five groups: instrumental, social, environmental, dietary, and anatomo-physiological. The instrumental hypotheses are based on the logic that evolutionary selection for larger brains is beneficial for species survival, dominance, and spread, because larger brains facilitate food-finding and mating success. The social hypotheses suggest that social behavior stimulates evolutionary expansion of brain size. Similarly, the environmental hypotheses suppose that encephalization is promoted by environmental factors such as stress, variability, and consistency. The dietary theories maintain that food quality and certain nutritional components directly contributed to the brain growth in the Homo genus. The anatomo-physiologic concepts, such as cranio-cerebral vascular hypertension due to head-down posture of the anthropoid fetus during pregnancy, are primarily focused on anatomic-functional changes that predispose to brain enlargement.

No single theory can completely account for human brain evolution. Multiple selective pressures in combination seems to have been involved. Synthetic theories have been proposed, but have not clearly explained reasons for the uniqueness of the human brain. Puzzlingly, brain enlargement has been found to have occurred independently in different primate lineages, but only human lineage ended up with an exceptional brain capacity. Fetal head-down posture may be an explanation of this conundrum because Homo sapiens is the only primate obligatory biped with upright posture.