Matrix-assisted laser desorption/ionization

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https://en.wikipedia.org/wiki/Matrix-assisted_laser_desorption/ionization 

MALDI TOF mass spectrometer

In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy-absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of biomolecules (biopolymers such as DNA, proteins, peptides and carbohydrates) and various organic molecules (such as polymers, dendrimers and other macromolecules), which tend to be fragile and fragment when ionized by more conventional ionization methods. It is similar in character to electrospray ionization (ESI) in that both techniques are relatively soft (low fragmentation) ways of obtaining ions of large molecules in the gas phase, though MALDI typically produces far fewer multi-charged ions.

MALDI methodology is a three-step process. First, the sample is mixed with a suitable matrix material and applied to a metal plate. Second, a pulsed laser irradiates the sample, triggering ablation and desorption of the sample and matrix material. Finally, the analyte molecules are ionized by being protonated or deprotonated in the hot plume of ablated gases, and then they can be accelerated into whichever mass spectrometer is used to analyse them.

History

Main article: History of mass spectrometry

The term matrix-assisted laser desorption ionization (MALDI) was coined in 1985 by Franz Hillenkamp, Michael Karas and their colleagues. These researchers found that the amino acid alanine could be ionized more easily if it was mixed with the amino acid tryptophan and irradiated with a pulsed 266 nm laser. The tryptophan was absorbing the laser energy and helping to ionize the non-absorbing alanine. Peptides up to the 2843 Da peptide melittin could be ionized when mixed with this kind of "matrix". The breakthrough for large molecule laser desorption ionization came in 1987 when Koichi Tanaka of Shimadzu Corporation and his co-workers used what they called the "ultra fine metal plus liquid matrix method" that combined 30 nm cobalt particles in glycerol with a 337 nm nitrogen laser for ionization. Using this laser and matrix combination, Tanaka was able to ionize biomolecules as large as the 34,472 Da protein carboxypeptidase-A. Tanaka received one-quarter of the 2002 Nobel Prize in Chemistry for demonstrating that, with the proper combination of laser wavelength and matrix, a protein can be ionized. Karas and Hillenkamp were subsequently able to ionize the 67 kDa protein albumin using a nicotinic acid matrix and a 266 nm laser. Further improvements were realized through the use of a 355 nm laser and the cinnamic acid derivatives ferulic acid, caffeic acid and sinapinic acid as the matrix. The availability of small and relatively inexpensive nitrogen lasers operating at 337 nm wavelength and the first commercial instruments introduced in the early 1990s brought MALDI to an increasing number of researchers. Today, mostly organic matrices are used for MALDI mass spectrometry.

Matrix

UV MALDI matrix list

Compound	Other names	Solvent	Wavelength (nm)	Applications
2,5-dihydroxy benzoic acid (gentisic acid)	DHB, gentisic acid	acetonitrile, water, methanol, acetone, chloroform	337, 355, 266	peptides, nucleotides, oligonucleotides, oligosaccharides
3,5-dimethoxy-4-hydroxycinnamic acid	sinapic acid; sinapinic acid; SA	acetonitrile, water, acetone, chloroform	337, 355, 266	peptides, proteins, lipids
4-hydroxy-3-methoxycinnamic acid	ferulic acid	acetonitrile, water, propanol	337, 355, 266	proteins
α-cyano-4-hydroxycinnamic acid	CHCA	acetonitrile, water, ethanol, acetone	337, 355	peptides, lipids, nucleotides
Picolinic acid	PA	Ethanol	266	oligonucleotides
3-hydroxy picolinic acid	HPA	Ethanol	337, 355	oligonucleotides

The matrix consists of crystallized molecules, of which the three most commonly used are sinapinic acid, α-cyano-4-hydroxycinnamic acid (α-CHCA, alpha-cyano or alpha-matrix) and 2,5-dihydroxybenzoic acid (DHB).^[16] A solution of one of these molecules is made, often in a mixture of highly purified water and an organic solvent such as acetonitrile (ACN) or ethanol. A counter ion source such as trifluoroacetic acid (TFA) is usually added to generate the [M+H] ions. A good example of a matrix-solution would be 20 mg/mL sinapinic acid in ACN:water:TFA (50:50:0.1).

Notation for cinnamic acid substitutions

The identification of suitable matrix compounds is determined to some extent by trial and error, but they are based on some specific molecular design considerations. They are of a fairly low molecular weight (to allow easy vaporization), but are large enough (with a low enough vapor pressure) not to evaporate during sample preparation or while standing in the mass spectrometer. They are often acidic, therefore act as a proton source to encourage ionization of the analyte. Basic matrices have also been reported. They have a strong optical absorption in either the UV or IR range, so that they rapidly and efficiently absorb the laser irradiation. This efficiency is commonly associated with chemical structures incorporating several conjugated double bonds, as seen in the structure of cinnamic acid. They are functionalized with polar groups, allowing their use in aqueous solutions. They typically contain a chromophore.

The matrix solution is mixed with the analyte (e.g. protein-sample). A mixture of water and organic solvent allows both hydrophobic and water-soluble (hydrophilic) molecules to dissolve into the solution. This solution is spotted onto a MALDI plate (usually a metal plate designed for this purpose). The solvents vaporize, leaving only the recrystallized matrix, but now with analyte molecules embedded into MALDI crystals. The matrix and the analyte are said to be co-crystallized. Co-crystallization is a key issue in selecting a proper matrix to obtain a good quality mass spectrum of the analyte of interest.

In analysis of biological systems, inorganic salts, which are also part of protein extracts, interfere with the ionization process. The salts can be removed by solid phase extraction or by washing the dried-droplet MALDI spots with cold water. Both methods can also remove other substances from the sample. The matrix-protein mixture is not homogeneous because the polarity difference leads to a separation of the two substances during co-crystallization. The spot diameter of the target is much larger than that of the laser, which makes it necessary to make many laser shots at different places of the target, to get the statistical average of the substance concentration within the target spot.

Naphthalene and naphthalene-like compounds can also be used as a matrix to ionize a sample.

The matrix can be used to tune the instrument to ionize the sample in different ways. As mentioned above, acid-base like reactions are often utilized to ionize the sample, however, molecules with conjugated pi systems, such as naphthalene like compounds, can also serve as an electron acceptor and thus a matrix for MALDI/TOF. This is particularly useful in studying molecules that also possess conjugated pi systems. The most widely used application for these matrices is studying porphyrin-like compounds such as chlorophyll. These matrices have been shown to have better ionization patterns that do not result in odd fragmentation patterns or complete loss of side chains. It has also been suggested that conjugated porphyrin like molecules can serve as a matrix and cleave themselves eliminating the need for a separate matrix compound.

Instrumentation

Diagram of a MALDI TOF instrument. Sample matrix ionized by radiant energy is ejected from surface. Sample travels into mass analyzer and is substantially detected.

There are several variations of the MALDI technology and comparable instruments are today produced for very different purposes, from more academic and analytical, to more industrial and high throughput. The mass spectrometry field has expanded into requiring ultrahigh resolution mass spectrometry such as the FT-ICR instruments as well as more high-throughput instruments. As many MALDI MS instruments can be bought with an interchangeable ionization source (electrospray ionization, MALDI, atmospheric pressure ionization, etc.) the technologies often overlap and many times any soft ionization method could potentially be used. For more variations of soft ionization methods see: Soft laser desorption or Ion source.

Laser

MALDI techniques typically employ the use of UV lasers such as nitrogen lasers (337 nm) and frequency-tripled and quadrupled Nd:YAG lasers (355 nm and 266 nm respectively).

Infrared laser wavelengths used for infrared MALDI include the 2.94 μm Er:YAG laser, mid-IR optical parametric oscillator, and 10.6 μm carbon dioxide laser. Although not as common, infrared lasers are used due to their softer mode of ionization. IR-MALDI also has the advantage of greater material removal (useful for biological samples), less low-mass interference, and compatibility with other matrix-free laser desorption mass spectrometry methods.

Time of flight

Sample target for a MALDI mass spectrometer

The type of a mass spectrometer most widely used with MALDI is the time-of-flight mass spectrometer (TOF), mainly due to its large mass range. The TOF measurement procedure is also ideally suited to the MALDI ionization process since the pulsed laser takes individual 'shots' rather than working in continuous operation. MALDI-TOF instruments are often equipped with a reflectron (an "ion mirror") that reflects ions using an electric field. This increases the ion flight path, thereby increasing time of flight between ions of different m/z and increasing resolution. Modern commercial reflectron TOF instruments reach a resolving power m/Δm of 50,000 FWHM (full-width half-maximum, Δm defined as the peak width at 50% of peak height) or more.

MALDI has been coupled with IMS-TOF MS to identify phosphorylated and non-phosphorylated peptides.

MALDI-FT-ICR MS has been demonstrated to be a useful technique where high resolution MALDI-MS measurements are desired.

Atmospheric pressure

Atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) is an ionization technique (ion source) that in contrast to vacuum MALDI operates at normal atmospheric environment. The main difference between vacuum MALDI and AP-MALDI is the pressure in which the ions are created. In vacuum MALDI, ions are typically produced at 10 mTorr or less while in AP-MALDI ions are formed in atmospheric pressure. In the past, the main disadvantage of the AP-MALDI technique compared to the conventional vacuum MALDI has been its limited sensitivity; however, ions can be transferred into the mass spectrometer with high efficiency and attomole detection limits have been reported. AP-MALDI is used in mass spectrometry (MS) in a variety of applications ranging from proteomics to drug discovery. Popular topics that are addressed by AP-MALDI mass spectrometry include: proteomics; mass analysis of DNA, RNA, PNA, lipids, oligosaccharides, phosphopeptides, bacteria, small molecules and synthetic polymers, similar applications as available also for vacuum MALDI instruments. The AP-MALDI ion source is easily coupled to an ion trap mass spectrometer or any other MS system equipped with electrospray ionization (ESI) or nanoESI source.

MALDI with ionization at reduced pressure is known to produce mainly singly-charged ions (see "Ionization mechanism" below). In contrast, ionization at atmospheric pressure can generate highly-charged analytes as was first shown for infrared  and later also for nitrogen lasers. Multiple charging of analytes is of great importance, because it allows to measure high-molecular-weight compounds like proteins in instruments, which provide only smaller m/z detection ranges such as quadrupoles. Besides the pressure, the composition of the matrix is important to achieve this effect.

Aerosol

In aerosol mass spectrometry, one of the ionization techniques consists in firing a laser to individual droplets. These systems are called single particle mass spectrometers (SPMS). The sample may optionally be mixed with a MALDI matrix prior to aerosolization.

Ionization mechanism

The laser is fired at the matrix crystals in the dried-droplet spot. The matrix absorbs the laser energy and it is thought that primarily the matrix is desorbed and ionized (by addition of a proton) by this event. The hot plume produced during ablation contains many species: neutral and ionized matrix molecules, protonated and deprotonated matrix molecules, matrix clusters and nanodroplets. Ablated species may participate in the ionization of analyte, though the mechanism of MALDI is still debated. The matrix is then thought to transfer protons to the analyte molecules (e.g., protein molecules), thus charging the analyte. An ion observed after this process will consist of the initial neutral molecule [M] with ions added or removed. This is called a quasimolecular ion, for example [M+H]⁺ in the case of an added proton, [M+Na]⁺ in the case of an added sodium ion, or [M-H]⁻ in the case of a removed proton. MALDI is capable of creating singly charged ions or multiply charged ions ([M+nH]ⁿ⁺) depending on the nature of the matrix, the laser intensity, and/or the voltage used. Note that these are all even-electron species. Ion signals of radical cations (photoionized molecules) can be observed, e.g., in the case of matrix molecules and other organic molecules.

The gas phase proton transfer model, implemented as the coupled physical and chemical dynamics (CPCD) model, of UV laser MALDI postulates primary and secondary processes leading to ionization. Primary processes involve initial charge separation through absorption of photons by the matrix and pooling of the energy to form matrix ion pairs. Primary ion formation occurs through absorption of a UV photon to create excited state molecules by

S₀ + hν → S₁

S₁ + S₁ → S₀ + S_n

S₁ + S_n → M⁺ + M⁻

where S₀ is the ground electronic state, S₁ the first electronic excited state, and S_n is a higher electronic excited state. The product ions can be proton transfer or electron transfer ion pairs, indicated by M⁺ and M⁻ above. Secondary processes involve ion-molecule reactions to form analyte ions.

In the lucky survivor model, positive ions can be formed from highly charged clusters produced during break-up of the matrix- and analyte-containing solid.

The lucky survivor model (cluster ionization mechanism) postulates that analyte molecules are incorporated in the matrix maintaining the charge state from solution. Ion formation occurs through charge separation upon fragmentation of laser ablated clusters. Ions that are not neutralized by recombination with photoelectrons or counter ions are the so-called lucky survivors.

The thermal model postulates that the high temperature facilitates the proton transfer between matrix and analyte in melted matrix liquid. Ion-to-neutral ratio is an important parameter to justify the theoretical model, and the mistaken citation of ion-to-neutral ratio could result in an erroneous determination of the ionization mechanism. The model quantitatively predicts the increase in total ion intensity as a function of the concentration and proton affinity of the analytes, and the ion-to-neutral ratio as a function of the laser fluences. This model also suggests that metal ion adducts (e.g., [M+Na]⁺ or [M+K]⁺) are mainly generated from the thermally induced dissolution of salt.

The matrix-assisted ionization (MAI) method uses matrix preparation similar to MALDI but does not require laser ablation to produce analyte ions of volatile or nonvolatile compounds. Simply exposing the matrix with analyte to the vacuum of the mass spectrometer creates ions with nearly identical charge states to electrospray ionization. It is suggested that there are likely mechanistic commonality between this process and MALDI.

Ion yield is typically estimated to range from 10⁻⁴ to 10⁻⁷, with some experiments hinting to even lower yields of 10⁻⁹. The issue of low ion yields had been addressed, already shortly after introduction of MALDI by various attempts, including post-ionization utilizing a second laser. Most of these attempts showed only limited success, with low signal increases. This might be attributed to the fact that axial time-of-flight instruments were used, which operate at pressures in the source region of 10⁻⁵ to 10⁻⁶, which results in rapid plume expansion with particle velocities of up to 1000 m/s. In 2015, successful laser post-ionization was reported, using a modified MALDI source operated at an elevated pressure of ~3 mbar coupled to an orthogonal time-of-flight mass analyzer, and employing a wavelength-tunable post-ionization laser, operated at wavelength from 260 nm to 280 nm, below the two-photon ionization threshold of the matrices used, which elevated ion yields of several lipids and small molecules by up to three orders of magnitude. This approach, called MALDI-2, due to the second laser, and the second MALDI-like ionization process, was afterwards adopted for other mass spectrometers, all equipped with sources operating in the low mbar range.

Applications

Biochemistry

In proteomics, MALDI is used for the rapid identification of proteins isolated by using gel electrophoresis: SDS-PAGE, size exclusion chromatography, affinity chromatography, strong/weak ion exchange, isotope coded protein labeling (ICPL), and two-dimensional gel electrophoresis. Peptide mass fingerprinting is the most popular analytical application of MALDI-TOF mass spectrometers. MALDI TOF/TOF mass spectrometers are used to reveal amino acid sequence of peptides using post-source decay or high energy collision-induced dissociation (further use see mass spectrometry).

MALDI-TOF have been used to characterise post-translational modifications. For example, it has been widely applied to study protein methylation and demethylation. However, care must be taken when studying post-translational modifications by MALDI-TOF. For example, it has been reported that loss of sialic acid has been identified in papers when dihydroxybenzoic acid (DHB) has been used as a matrix for MALDI MS analysis of glycosylated peptides. Using sinapinic acid, 4-HCCA and DHB as matrices, S. Martin studied loss of sialic acid in glycosylated peptides by metastable decay in MALDI/TOF in linear mode and reflector mode. A group at Shimadzu Corporation derivatized the sialic acid by an amidation reaction as a way to improve detection sensitivity and also demonstrated that ionic liquid matrix reduces a loss of sialic acid during MALDI/TOF MS analysis of sialylated oligosaccharides. THAP, DHAP, and a mixture of 2-aza-2-thiothymine and phenylhydrazine have been identified as matrices that could be used to minimize loss of sialic acid during MALDI MS analysis of glycosylated peptides. It has been reported that a reduction in loss of some post-translational modifications can be accomplished if IR MALDI is used instead of UV MALDI.

Besides proteins, MALDI-TOF has also been applied to study lipids. For example, it has been applied to study the catalytic reactions of phospholipases. In addition to lipids, oligonucleotides have also been characterised by MALDI-TOF. For example, in molecular biology, a mixture of 5-methoxysalicylic acid and spermine can be used as a matrix for oligonucleotides analysis in MALDI mass spectrometry, for instance after oligonucleotide synthesis.

Organic chemistry

Some synthetic macromolecules, such as catenanes and rotaxanes, dendrimers and hyperbranched polymers, and other assemblies, have molecular weights extending into the thousands or tens of thousands, where most ionization techniques have difficulty producing molecular ions. MALDI is a simple and fast analytical method that can allow chemists to rapidly analyze the results of such syntheses and verify their results.

Polymers

In polymer chemistry, MALDI can be used to determine the molar mass distribution. Polymers with polydispersity greater than 1.2 are difficult to characterize with MALDI due to the signal intensity discrimination against higher mass oligomers.

A good matrix for polymers is dithranol or AgTFA. The sample must first be mixed with dithranol and the AgTFA added afterwards; otherwise the sample will precipitate out of solution.

Microbiology

Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England community hospital setting. MALDI-TOF is seen in multiple situations in the "same day tests" row at center-bottom.

MALDI-TOF spectra are often used for the identification of microorganisms such as bacteria or fungi. A portion of a colony of the microbe in question is placed onto the sample target and overlaid with matrix. The mass spectra of expressed proteins generated are analyzed by dedicated software and compared with stored profiles for species determination in what is known as biotyping. It offers benefits to other immunological or biochemical procedures and has become a common method for species identification in clinical microbiological laboratories. Benefits of high resolution MALDI-MS performed on a Fourier transform ion cyclotron resonance mass spectrometry (also known as FT-MS) have been demonstrated for typing and subtyping viruses though single ion detection known as proteotyping, with a particular focus on influenza viruses.

One main advantage over other microbiological identification methods is its ability to rapidly and reliably identify, at low cost, a wide variety of microorganisms directly from the selective medium used to isolate them. The absence of the need to purify the suspect or "presumptive" colony allows for a much faster turn-around times. For example, it has been demonstrated that MALDI-TOF can be used to detect bacteria directly from blood cultures.

Another advantage is the potential to predict antibiotic susceptibility of bacteria. A single mass spectral peak can predict methicillin resistance of Staphylococcus aureus. MALDI can also detect carbapenemase of carbapenem-resistant enterobacteriaceae, including Acinetobacter baumannii and Klebsiella pneumoniae. However, most proteins that mediate antibiotic resistance are larger than MALDI-TOF's 2000–20,000 Da range for protein peak interpretation and only occasionally, as in the 2011 Klebsiella pneumoniae carbapenemase (KPC) outbreak at the NIH, a correlation between a peak and resistance conferring protein can be made.

Parasitology

MALDI-TOF spectra have been used for the detection and identification of various parasites such as trypanosomatids, Leishmania and Plasmodium. In addition to these unicellular parasites, MALDI/TOF can be used for the identification of parasitic insects such as lice or cercariae, the free-swimming stage of trematodes.

Medicine

MALDI-TOF spectra are often utilized in tandem with other analysis and spectroscopy techniques in the diagnosis of diseases. MALDI/TOF is a diagnostic tool with much potential because it allows for the rapid identification of proteins and changes to proteins without the cost or computing power of sequencing nor the skill or time needed to solve a crystal structure in X-ray crystallography.

One example of this is necrotizing enterocolitis (NEC), which is a devastating disease that affects the bowels of premature infants. The symptoms of NEC are very similar to those of sepsis, and many infants die awaiting diagnosis and treatment. MALDI/TOF was used to identify bacteria present in the fecal matter of NEC positive infants. This study focused on characterization of the fecal microbiota associated with NEC and did not address the mechanism of disease. There is hope that a similar technique could be used as a quick, diagnostic tool that would not require sequencing.

Another example of the diagnostic power of MALDI/TOF is in the area of cancer. Pancreatic cancer remains one of the most deadly and difficult to diagnose cancers. Impaired cellular signaling due to mutations in membrane proteins has been long suspected to contribute to pancreatic cancer. MALDI/TOF has been used to identify a membrane protein associated with pancreatic cancer and at one point may even serve as an early detection technique.

MALDI/TOF can also potentially be used to dictate treatment as well as diagnosis. MALDI/TOF serves as a method for determining the drug resistance of bacteria, especially to β-lactams (Penicillin family). The MALDI/TOF detects the presence of carbapenemases, which indicates drug resistance to standard antibiotics. It is predicted that this could serve as a method for identifying a bacterium as drug resistant in as little as three hours. This technique could help physicians decide whether to prescribe more aggressive antibiotics initially.

Detection of protein complexes

Following initial observations that some peptide-peptide complexes could survive MALDI deposition and ionization, studies of large protein complexes using MALDI-MS have been reported.

Small molecules

While MALDI is a common technique for large macro-molecules, it is often possible to also analyze small molecules with mass below 1000 Da.  The problem with small molecules is that of matrix effects, where signal interference, detector saturation, or suppression of the analyte signal is possible since the matrices often consists of small molecules themselves. The choice of matrix is highly dependent on what molecules are to be analyzed.

MALDI-imaging mass spectrometry

Due to MALDI being a soft ionization source, it is used on a wide variety of biomolecules. This has led to it being used in new ways such as MALDI-imaging mass spectrometry. This technique allows for the imaging of the spatial distribution of biomolecules.

Philosophy of psychedelics

From Wikipedia, the free encyclopedia

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

Philosophy of psychedelics is the philosophical investigation of the psychedelic experience. While psychedelic, entheogenic or hallucinogenic substances have been used by many traditional cultures throughout history mostly for religious purposes, recorded philosophical speculation and analysis of these substances, their phenomenological effects and the relevance of these altered states of consciousness to philosophical questions is a relatively late phenomenon in the history of philosophy. Traditional cultures who use psychedelic substances such as the Amazonian and Indigenous Mexican peoples hold that ingesting medicinal plants such as Ayahuasca and Peyote allows one to commune with the beings of the spirit world.

Indian philosophy

The Indian Yogi and scholar Patanjali in his Yoga sutras (4.1) mentions that mystic powers (siddhaya) can arise from certain "herbs" or "healing plants" (osadhi):

janmauṣadhi-mantra-tapaḥ samādhi jāḥ siddhayaḥ||

The mystic powers arise due to birth, herbs, mantras, the performance of austerity and samadhi.

Later commentators on the Yoga sutras like Vyasa mention elixirs of the asuras, and also state these herbal concoctions can be found in this world. Adi Shankara meanwhile refers to the Vedic drink Soma.

Vajrayana Buddhist Tantras mention the nectar "amrita" (literally "immortal", "deathless") which was drunk during rituals and which is associated in the tradition with 'spiritual intoxication'. A biography of the scholar Gampopa mentions how one of his teachers stated that "You can obtain Buddhahood: by taking a medicine pill which will make you immortal like the sun and moon." This is a reference to the Vajrayana practice of rasayana (Skt: "alchemy") to create certain potions or pills. According to M.L. Walter's study of Indo-Tibetan rasayana, ingestion of these substances were said to "strengthen the yogin and procure the siddhi for him, as well as bringing him to the final goal." According to Chogyam Trungpa (1939–1987), a modern teacher in the Kagyu tradition:

amrita... is used in conferring the second abhisheka, the secret abhisheka. This transmission dissolves the student's mind into the mind of the teacher of the lineage. In general, amrita is the principle of intoxicating extreme beliefs, belief in ego, and dissolving the boundary between confusion and sanity so that coemergence can be realized.

19th century

European literature such as Confessions of an English Opium-Eater by Thomas De Quincey (one of the first English commentators on Kant)^[7] and Samuel Taylor Coleridge's "Kubla Khan" described the use and phenomenal character of mind-altering substances such as opium. De Quincey held that opium allowed one to access the earliest of memories and that therefore no memories were ever truly forgotten:

The minutest incidents of childhood, or forgotten scenes of later years, were often revived: I could not be said to recollect them; for if I had been told of them when waking, I should not have been able to acknowledge them as parts of my past experience. But placed as they were before me, in dreams like intuitions, and clothed in all their evanescent circumstances and accompanying feelings, I recognized them instantaneously […] I feel assured that there is no such thing as forgetting possible to the mind.

Jacques-Joseph Moreau, who reported his experiments with mental patients and drugs, believed that "the hashish experience was a way to gain insight into mental disease."

The French Poet Baudelaire wrote about the effects of hashish and opium in Les Paradis artificiels (1860) and theorized about how they could be used to allow the individual to reach "ideal" states of mind. Charles Baudelaire was member of the "Club des Hashischins", a Parisian literary group dedicated to the exploration of altered states of consciousness which included Jacques-Joseph Moreau and literary figures such as Victor Hugo, Alexandre Dumas, Gerard de Nerval, Honore de Balzac, and Theophile Gautier. Baudelaire's opinion of the drug was generally negative, believing that it weakened and dampened artistic capacities, the personal Will and even the very identity of the hashish eater. He compared it to suicide and a false happiness, and saw wine as the true intoxicant of the artists.

In the United States, The Hasheesh Eater (1857), an autobiographical book by Fitz Hugh Ludlow, became popular. Ludlow wrote that a marijuana user sought "the soul’s capacity for a broader being, deeper insight, grander views of Beauty, Truth and Good than she now gains through the chinks of her cell." The American William James was one of the first academic philosophers to write about the effects of hallucinogenic substances in his The Subjective Effects of Nitrous Oxide (1882) in which he writes that the gas can produce a "tremendously exciting sense of an intense metaphysical illumination. Truth lies open to the view in depth beneath depth of almost blinding evidence. The mind sees all logical relations of being with an apparent subtlety and instantaniety to which its normal consciousness offers no parallel". He goes on to say that the experience gave him the sense that the philosophy of Hegel was true. In his The Varieties of Religious Experience he likewise writes:

Nitrous oxide and ether, especially nitrous oxide … stimulate the mystical consciousness in an extraordinary degree. … [In] the nitrous oxide trance we have a genuine metaphysical revelation. … [Our] normal waking consciousness, rational consciousness as we call it, is but one special type of consciousness, whilst all about it, parted from it by the filmiest of screens, there lie potential forms of consciousness entirely different.

While it has been speculated that Friedrich Nietzsche had psychedelic experiences brought on by the drugs he used to help with his various illnesses, it is more likely that his drug use was restricted to opium, rather than classic psychedelics. He had, however, speculated on the significance of altered states, particularly with regards to "narcotics potions" taken to attain oneness with one's fellow man and with nature. In The Birth of Tragedy he wrote:

"Now that the gospel of universal harmony is sounded, each individual becomes not only reconciled to his fellow but actually at one with him - as though the veil of Maya had been torn apart and there remained only shreds floating before the vision of mystical Oneness."

20th century

After using mescaline in 1953, Aldous Huxley wrote The Doors of Perception where he advanced the theory that psychedelic compounds could produce mystical experiences and knowledge, "what the visionary, the medium, even the mystic were talking about" and what Eastern philosophy described with terms like satcitananda, godhead, suchness, shunyata, anatta and dharmakaya. Huxley also quotes the philosopher C. D. Broad, who held that the brain and nervous system might act as a reducing valve of all the stimuli in the universe:

According to such a theory, each one of us is potentially Mind at Large. But in so far as we are animals, our business is at all costs to survive. To make biological survival possible, Mind at Large has to be funneled through the reducing valve of the brain and nervous system. What comes out at the other end is a measly trickle of the kind of consciousness which will help us to stay alive on the surface of this Particular planet.

Huxley wrote that it was possible that certain human beings could, through drugs, meditation, etc. circumvent the reducing valve and experience something far beyond everyday consciousness. This experience Huxley saw as the source of all mysticism, a theory termed the perennial philosophy. He also discusses art and the legality of various drugs in the West as well as arguing for the importance for self-transcendence. Huxley's philosophical novel Island also described a utopian society that used a psychedelic substance for spiritual purposes.

In the early 1960s a group that eventually came to be called "Harvard Psychedelic Club" which included Timothy Leary, Huston Smith and Ram Dass administered psychedelics to Harvard students. The group experimented with psychedelics in experiments such as the Harvard Psilocybin Project. Huston Smith's last work, Cleansing the Doors of Perception, describes the Harvard Project in which he participated.

Ram Dass' Be Here Now and Timothy Leary's The Psychedelic Experience: A Manual Based on The Tibetan Book of the Dead compared the psychedelic experiences to Eastern philosophy and mystical states of consciousness. These books further popularized the idea that Eastern – particularly Indian – philosophical and spiritual insights could be obtained from using psychedelics. One of these experiences described in The Psychedelic Experience is that of ego death or depersonalization.

The idea that the psychedelic experience could grant access to eastern spiritual insights was also promoted by the popular philosopher Alan Watts in his writings such as The Joyous Cosmology, who also argued that one should not remain dependent on them for spiritual growth: "If you get the message, hang up the phone. For psychedelic drugs are simply instruments, like microscopes, telescopes, and telephones. The biologist does not sit with eye permanently glued to the microscope, he goes away and works on what he has seen."

Various psychologists during the 1960s also studied psychedelic substances and worked with psychedelic therapy and later developed various theories about their effects and significance. Stanislav Grof is known for his extensive work in LSD psychotherapy and for developing a theory which stated that the psychedelic experience allowed one to relive birth trauma and to explore the depths of the unconscious mind. Grof observed four levels of the LSD experience, which for him correspond to areas of the human unconscious: (1) abstract and aesthetic experiences (2) psychodynamic experiences (3) perinatal experiences, and (4) transpersonal experiences. Grof defined the last level as "experiences involving an expansion or extension of consciousness beyond the usual ego boundaries and beyond the limitations of time and/or space." The field of transpersonal psychology focuses on this type of experience. Grof included topics such as consciousness, mysticism and metaphysics in his later writings.

The scientist and philosopher John C. Lilly discussed his experiments with psychedelics and altered states of consciousness in The Center of the Cyclone: An Autobiography of Inner Space and Programming and Metaprogramming in the Human Biocomputer. Other psychologists who studied and wrote on psychedelic use include Walter Pahnke, Ralph Metzner and Claudio Naranjo.

According to writer James Oroc, the 1990s brought about a second phase in modern psychedelic culture. The philosophical foundation of this new wave of psychedelic thought was based on the works of Alexander Shulgin, Alex Grey and Terence McKenna.

Contemporary

Academic

Neuroscientist Rick Strassman has written about his research into the psychedelic N,N-Dimethyltryptamine in his book DMT: The Spirit Molecule (2001). In his book Strassman investigates the possible connection between natural DMT in mystical and Near Death Experiences and psychedelic states caused by outwardly administered DMT. He also describes the psychedelic experiences of the volunteers in his experiments and their encounter with certain strange "beings" after being administered DMT.

The philosopher Thomas Metzinger has discussed the effects of substances such as LSD, dimethyltryptamine, and mescaline in his Being No One (2003) and those of psilocybin in The Ego Tunnel (2009). Metzinger describes the hallucinatory component of the psychedelic experience as "epistemically vacuous," i.e., not a reliable source of knowledge.

In 2012, University of California Press published the book Neuropsychedelia by anthropologist Nicolas Langlitz. In this book, Langlitz recounts the findings of his fieldwork following scientists involved in reviving scientific research on psychedelics as well as his own philosophical reflections. He explains that Aldous Huxley's view expressed in The Doors of Perception—of the brain as a "reducing valve" which when released by the ingestion of a psychedelics produces a "perennial" mystical experience—has been very influential among contemporary psychopharmacologists. These scientists, Langlitz writes, have given Huxley's view a materialist "neurobiological reinterpretation" which Langlitz calls "mystic materialism".

In 2021, the philosopher Chris Letheby's book Philosophy of Psychedelics was published by Oxford University Press. Philosophy of Psychedelics is organised as a defence against what Letheby calls the "Comforting Delusion Objection" to psychedelic therapy. The objection is that psychedelic therapy works by inducing non-naturalistic metaphysical beliefs, and so it is epistemically deficient if one adopts a philosophically naturalistic world-view. Letheby concludes that the Comforting Delusion Objection fails, and that the epistemic status of psychedelic therapy, given philosophical naturalism, is good.

In 2022, Christine Hauskeller and Peter Sjöstedt-Hughes' edited volume, Philosophy and Psychedelics: Frameworks for Exceptional Experience was published by Bloomsbury Academic.

Other contemporary academics writing on the philosophy of psychedelics include Sarah Lane Ritchie, Aidan Lyon, and Anya Farennikova.

Popular

In his non-academic encyclopedia of psychedelic culture and thought Psychedelia (2012), Patrick Lundborg developed a psychedelic philosophy he called "Unified Psychedelic Theory" (UPT) which draws from Platonism, the phenomenology of Husserl and Merleau-Ponty, Paul D. MacLean's Triune brain theory, the work of Eugen Fink, and other thinkers.

The American author Sam Harris discussed his use of psychedelics in his 2014 book Waking Up: A Guide to Spirituality Without Religion, which argues for a naturalized spirituality.

The philosopher Peter Sjöstedt-Hughes' book Noumenautics was published by the independent publisher Psychedelic Press in 2015 and discusses psychedelic phenomenology and its metaphysical implications. In 2021 they published his Modes of Sentience covering similar themes.

Four-dimensionalism

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Four-dimensionalism

In philosophy, four-dimensionalism (also known as the doctrine of temporal parts) is the ontological position that an object's persistence through time is like its extension through space. Thus, an object that exists in time has temporal parts in the various subregions of the total region of time it occupies, just like an object that exists in a region of space has at least one part in every subregion of that space.

Four-dimensionalists typically argue for treating time as analogous to space, usually leading them to endorse the doctrine of eternalism. This is a philosophical approach to the ontological nature of time, according to which all points in time are equally "real", as opposed to the presentist idea that only the present is real. As some eternalists argue by analogy, just as all spatially distant objects and events are as real as those close to us, temporally distant objects and events are as real as those currently present to us.

Perdurantism—or perdurance theory—is a closely related philosophical theory of persistence and identity, according to which an individual has distinct temporal parts throughout its existence, and the persisting object is the sum or set of all of its temporal parts. This sum or set is colloquially referred to as a "space-time worm", which has earned the perdurantist view the moniker of "the worm view". While all perdurantists are plausibly considered four dimensionalists, at least one variety of four dimensionalism does not count as perdurantist in nature. This variety, known as exdurantism or the "stage view", is closely akin to the perdurantist position. They also countenance a view of persisting objects that have temporal parts that succeed one another through time. However, instead of identifying the persisting object as the entire set or sum of its temporal parts, the exdurantist argues that any object under discussion is a single stage (time-slice, temporal part, etc.), and that the other stages or parts that comprise the persisting object are related to that part by a "temporal counterpart" relation.

Though they have often been conflated, eternalism is a theory of what time is like and what times exist, while perdurantism is a theory about persisting objects and their identity conditions over time. Eternalism and perdurantism tend to be discussed together because many philosophers argue for a combination of eternalism and perdurantism. Sider (1997) uses the term four-dimensionalism to refer to perdurantism, but Michael Rea uses the term "four-dimensionalism" to mean the view that presentism is false as opposed to "perdurantism", the view that endurantism is false and persisting objects have temporal parts.

Four-dimensionalism about material objects

Four-dimensionalism is a name for different positions. One of these uses four-dimensionalism as a position of material objects with respect to dimensions. Four-dimensionalism is the view that in addition to spatial parts, objects have temporal parts.

According to this view, four-dimensionalism cannot be used as a synonym for perdurantism. Perdurantists have to hold a four-dimensional view of material objects: it is impossible that perdurantists, who believe that objects persist by having different temporal parts at different times, do not believe in temporal parts. However, the reverse is not true. Four-dimensionalism is compatible with either perdurantism or exdurantism.

A-series and B-series

Main article: A-series and B-series

J.M.E. McTaggart in The Unreality of Time identified two descriptions of time, which he called the A-series and the B-series. The A-series identifies positions in time as past, present, or future, and thus assumes that the "present" has some objective reality, as in both presentism and the growing block universe. The B-series defines a given event as earlier or later than another event, but does not assume an objective present, as in four-dimensionalism. Much of the contemporary literature in the metaphysics of time has been taken to spring forth from this distinction, and thus takes McTaggart's work as its starting point.

Contrast with three-dimensionalism

Unlike the four dimensionalist, the three dimensionalist considers time to be a unique dimension that is not analogous to the three spatial dimensions: length, width and height. Whereas the four dimensionalist proposes that objects are extended across time, the three dimensionalist adheres to the belief that all objects are wholly present at any moment at which they exist. While the three dimensionalist agrees that the parts of an object can be differentiated based on their spatial dimensions, they do not believe an object can be differentiated into temporal parts across time. For example, in the three dimensionalist account, "Descartes in 1635" is the same object as "Descartes in 1620", and both are identical to Descartes, himself. However, the four dimensionalist considers these to be distinct temporal parts.

Prominent arguments in favor of four-dimensionalism

Several lines of argumentation have been advanced in favor of four-dimensionalism:

Firstly, four-dimensional accounts of time are argued to better explain paradoxes of change over time (often referred to as the paradox of the Ship of Theseus) than three-dimensional theories. A contemporary account of this paradox is introduced in Ney (2014), but the original problem has its roots in Greek antiquity. A typical Ship of Theseus paradox involves taking some changeable object with multiple material parts, for example a ship, then sequentially removing and replacing its parts until none of the original components are left. At each stage of the replacement, the ship is presumably identical with the original, since the replacement of a single part need not destroy the ship and create an entirely new one. But, it is also plausible that an object with none of the same material parts as another is not identical with the original object. So, how can an object survive the replacement of any of its parts, and in fact all of its parts? The four-dimensionalist can argue that the persisting object is a single space-time worm which has all the replacement stages as temporal parts, or in the case of the stage view that each succeeding stage bears a temporal counterpart relation to the original stage under discussion.

Secondly, problems of temporary intrinsics are argued to be best explained by four-dimensional views of time that involve temporal parts. As presented by David Lewis, the problem of temporary intrinsics involves properties of an object that are both had by that object regardless of how anything else in the world is (and thus intrinsic), and subject to change over time (thus temporary). Shape is argued to be one such property. So, if an object is capable of having a particular shape, and also changing its shape at another time, there must be some way for the same object to be, say, both round and square. Lewis argues that separate temporal parts having the incompatible properties best explains an object being able to change its shape in this way, because other accounts of three-dimensional time eliminate intrinsic properties by indexing them to times and making them relational instead of intrinsic.

Convergent evolution

From Wikipedia, the free encyclopedia

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

 

Two succulent plant genera, Euphorbia and Astrophytum, are only distantly related, but the species within each have converged on a similar body form 

 

Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last common ancestor of those groups. The cladistic term for the same phenomenon is homoplasy. The recurrent evolution of flight is a classic example, as flying insects, birds, pterosaurs, and bats have independently evolved the useful capacity of flight. Functionally similar features that have arisen through convergent evolution are analogous, whereas homologous structures or traits have a common origin but can have dissimilar functions. Bird, bat, and pterosaur wings are analogous structures, but their forelimbs are homologous, sharing an ancestral state despite serving different functions.

The opposite of convergent evolution is divergent evolution, where related species evolve different traits. Convergent evolution is similar to parallel evolution, which occurs when two independent species evolve in the same direction and thus independently acquire similar characteristics; for instance, gliding frogs have evolved in parallel from multiple types of tree frog.

Many instances of convergent evolution are known in plants, including the repeated development of C₄ photosynthesis, seed dispersal by fleshy fruits adapted to be eaten by animals, and carnivory.

Overview

Homology and analogy in mammals and insects: on the horizontal axis, the structures are homologous in morphology, but different in function due to differences in habitat. On the vertical axis, the structures are analogous in function due to similar lifestyles but anatomically different with different phylogeny.

Further information: List of examples of convergent evolution

In morphology, analogous traits arise when different species live in similar ways and/or a similar environment, and so face the same environmental factors. When occupying similar ecological niches (that is, a distinctive way of life) similar problems can lead to similar solutions. The British anatomist Richard Owen was the first to identify the fundamental difference between analogies and homologies.

In biochemistry, physical and chemical constraints on mechanisms have caused some active site arrangements such as the catalytic triad to evolve independently in separate enzyme superfamilies.

In his 1989 book Wonderful Life, Stephen Jay Gould argued that if one could "rewind the tape of life [and] the same conditions were encountered again, evolution could take a very different course." Simon Conway Morris disputes this conclusion, arguing that convergence is a dominant force in evolution, and given that the same environmental and physical constraints are at work, life will inevitably evolve toward an "optimum" body plan, and at some point, evolution is bound to stumble upon intelligence, a trait presently identified with at least primates, corvids, and cetaceans.

Distinctions

Cladistics

Further information: Cladistics

In cladistics, a homoplasy is a trait shared by two or more taxa for any reason other than that they share a common ancestry. Taxa which do share ancestry are part of the same clade; cladistics seeks to arrange them according to their degree of relatedness to describe their phylogeny. Homoplastic traits caused by convergence are therefore, from the point of view of cladistics, confounding factors which could lead to an incorrect analysis.

Atavism

Further information: Atavism

It can be difficult to tell whether a trait has been lost and then re-evolved convergently, or whether a gene has simply been switched off and then re-enabled later. Such a re-emerged trait is called an atavism. From a mathematical standpoint, an unused gene (selectively neutral) has a steadily decreasing probability of retaining potential functionality over time. The time scale of this process varies greatly in different phylogenies; in mammals and birds, there is a reasonable probability of a gene's remaining in the genome in a potentially functional state for around 6 million years.

Parallel vs. convergent evolution

Evolution at an amino acid position. In each case, the left-hand species changes from having alanine (A) at a specific position in a protein in a hypothetical ancestor, and now has serine (S) there. The right-hand species may undergo divergent, parallel, or convergent evolution at this amino acid position relative to the first species.

When two species are similar in a particular character, evolution is defined as parallel if the ancestors were also similar, and convergent if they were not. Some scientists have argued that there is a continuum between parallel and convergent evolution, while others maintain that despite some overlap, there are still important distinctions between the two.

When the ancestral forms are unspecified or unknown, or the range of traits considered is not clearly specified, the distinction between parallel and convergent evolution becomes more subjective. For instance, the striking example of similar placental and marsupial forms is described by Richard Dawkins in The Blind Watchmaker as a case of convergent evolution, because mammals on each continent had a long evolutionary history prior to the extinction of the dinosaurs under which to accumulate relevant differences.

At molecular level

Evolutionary convergence of serine and cysteine protease towards the same catalytic triads organisation of acid-base-nucleophile in different protease superfamilies. Shown are the triads of subtilisin, prolyl oligopeptidase, TEV protease, and papain.

Proteins

Tertiary structures

Many proteins share analogous structural elements that arose independently across different genomes. There are several examples of convergent protein motifs sharing similar arrangements of structural elements. Whole protein structures too have arisen through convergent evolution.

Protease active sites

The enzymology of proteases provides some of the clearest examples of convergent evolution. These examples reflect the intrinsic chemical constraints on enzymes, leading evolution to converge on equivalent solutions independently and repeatedly.

Serine and cysteine proteases use different amino acid functional groups (alcohol or thiol) as a nucleophile. To activate that nucleophile, they orient an acidic and a basic residue in a catalytic triad. The chemical and physical constraints on enzyme catalysis have caused identical triad arrangements to evolve independently more than 20 times in different enzyme superfamilies.

Threonine proteases use the amino acid threonine as their catalytic nucleophile. Unlike cysteine and serine, threonine is a secondary alcohol (i.e. has a methyl group). The methyl group of threonine greatly restricts the possible orientations of triad and substrate, as the methyl clashes with either the enzyme backbone or the histidine base. Consequently, most threonine proteases use an N-terminal threonine in order to avoid such steric clashes. Several evolutionarily independent enzyme superfamilies with different protein folds use the N-terminal residue as a nucleophile. This commonality of active site but difference of protein fold indicates that the active site evolved convergently in those families.

Cone snail and fish insulin

Conus geographus produces a distinct form of insulin that is more similar to fish insulin protein sequences than to insulin from more closely related molluscs, suggesting convergent evolution, though with the possibility of horizontal gene transfer.

Ferrous iron uptake via protein transporters in land plants and chlorophytes

Distant homologues of the metal ion transporters ZIP in land plants and chlorophytes have converged in structure, likely to take up Fe²⁺ efficiently. The IRT1 proteins from Arabidopsis thaliana and rice have extremely different amino acid sequences from Chlamydomonas's IRT1, but their three-dimensional structures are similar, suggesting convergent evolution.

Na⁺,K⁺-ATPase and Insect resistance to cardiotonic steroids

Many examples of convergent evolution exist in insects in terms of developing resistance at a molecular level to toxins. One well-characterized example is the evolution of resistance to cardiotonic steroids (CTSs) via amino acid substitutions at well-defined positions of the α-subunit of Na⁺,K⁺-ATPase (ATPalpha). Variation in ATPalpha has been surveyed in various CTS-adapted species spanning six insect orders. Among 21 CTS-adapted species, 58 (76%) of 76 amino acid substitutions at sites implicated in CTS resistance occur in parallel in at least two lineages. 30 of these substitutions (40%) occur at just two sites in the protein (positions 111 and 122). CTS-adapted species have also recurrently evolved neo-functionalized duplications of ATPalpha, with convergent tissue-specific expression patterns.

Nucleic acids

Convergence occurs at the level of DNA and the amino acid sequences produced by translating structural genes into proteins. Studies have found convergence in amino acid sequences in echolocating bats and the dolphin; among marine mammals; between giant and red pandas; and between the thylacine and canids. Convergence has also been detected in a type of non-coding DNA, cis-regulatory elements, such as in their rates of evolution; this could indicate either positive selection or relaxed purifying selection.

In animals

Dolphins and ichthyosaurs converged on many adaptations for fast swimming.

Bodyplans

Swimming animals including fish such as herrings, marine mammals such as dolphins, and ichthyosaurs (of the Mesozoic) all converged on the same streamlined shape. A similar shape and swimming adaptations are even present in molluscs, such as Phylliroe. The fusiform bodyshape (a tube tapered at both ends) adopted by many aquatic animals is an adaptation to enable them to travel at high speed in a high drag environment. Similar body shapes are found in the earless seals and the eared seals: they still have four legs, but these are strongly modified for swimming.

The marsupial fauna of Australia and the placental mammals of the Old World have several strikingly similar forms, developed in two clades, isolated from each other. The body, and especially the skull shape, of the thylacine (Tasmanian tiger or Tasmanian wolf) converged with those of Canidae such as the red fox, Vulpes vulpes.

• Convergence of marsupial and placental mammals
• 
  Red fox skeleton
  
  
• 
  Skulls of thylacine (left), timber wolf (right)
   
• 
  Thylacine skeleton

Echolocation

As a sensory adaptation, echolocation has evolved separately in cetaceans (dolphins and whales) and bats, but from the same genetic mutations.

Electric fishes

The Gymnotiformes of South America and the Mormyridae of Africa independently evolved passive electroreception (around 119 and 110 million years ago, respectively). Around 20 million years after acquiring that ability, both groups evolved active electrogenesis, producing weak electric fields to help them detect prey.

• Convergence of weakly electric fishes
• 
  A gymnotiform electrolocation waveform
  
  
• 
  A gymnotiform electric fish of South America
• 
  A mormyrid electric fish of Africa
   
• 
  A mormyrid electrolocation waveform

Eyes

Main article: Eye evolution

The camera eyes of vertebrates (left) and cephalopods (right) developed independently and are wired differently; for instance, optic nerve ⁽³⁾ fibres ⁽²⁾ reach the vertebrate retina ⁽¹⁾ from the front, creating a blind spot ⁽⁴⁾.

One of the best-known examples of convergent evolution is the camera eye of cephalopods (such as squid and octopus), vertebrates (including mammals) and cnidarians (such as jellyfish). Their last common ancestor had at most a simple photoreceptive spot, but a range of processes led to the progressive refinement of camera eyes—with one sharp difference: the cephalopod eye is "wired" in the opposite direction, with blood and nerve vessels entering from the back of the retina, rather than the front as in vertebrates. As a result, vertebrates have a blind spot.

Sex organs

Hydrostatic penises have convergently evolved at least six times in male amniotes. In these species, males copulate with females and internally fertilize their eggs. Similar intromittent organs have evolved in invertebrates such as octopuses and gastropods.

Flight

Further information: Flying and gliding animals § Evolution and ecology of aerial locomotion

Vertebrate wings are partly homologous (from forelimbs), but analogous as organs of flight in (1) pterosaurs, (2) bats, (3) birds, evolved separately.

Birds and bats have homologous limbs because they are both ultimately derived from terrestrial tetrapods, but their flight mechanisms are only analogous, so their wings are examples of functional convergence. The two groups have independently evolved their own means of powered flight. Their wings differ substantially in construction. The bat wing is a membrane stretched across four extremely elongated fingers and the legs. The airfoil of the bird wing is made of feathers, strongly attached to the forearm (the ulna) and the highly fused bones of the wrist and hand (the carpometacarpus), with only tiny remnants of two fingers remaining, each anchoring a single feather. So, while the wings of bats and birds are functionally convergent, they are not anatomically convergent. Birds and bats also share a high concentration of cerebrosides in the skin of their wings. This improves skin flexibility, a trait useful for flying animals; other mammals have a far lower concentration. The extinct pterosaurs independently evolved wings from their fore- and hindlimbs, while insects have wings that evolved separately from different organs.

Flying squirrels and sugar gliders are much alike in their mammalian body plans, with gliding wings stretched between their limbs, but flying squirrels are placentals while sugar gliders are marsupials, widely separated within the mammal lineage from the placentals.

Hummingbird hawk-moths and hummingbirds have evolved similar flight and feeding patterns.

Insect mouthparts

Insect mouthparts show many examples of convergent evolution. The mouthparts of different insect groups consist of a set of homologous organs, specialised for the dietary intake of that insect group. Convergent evolution of many groups of insects led from original biting-chewing mouthparts to different, more specialised, derived function types. These include, for example, the proboscis of flower-visiting insects such as bees and flower beetles, or the biting-sucking mouthparts of blood-sucking insects such as fleas and mosquitos.

Intelligence

Further information: Cephalopod intelligence

Advanced intelligence has evolved independently in cephalopods and vertebrates. Octopus have demonstrated mammalian levels of problem-solving, cognition, and learning behaviors. One aquarium director even claimed his octopus specimen to have developed a sense of personal taste as to the arrangement of its tank. Unlike other highly intelligent animals, cephalopods typically live short lives with varying levels of sociality, with the bulk of the nervous system divided between the head and limbs.

Opposable thumbs

Opposable thumbs allowing the grasping of objects are most often associated with primates, like humans and other apes, monkeys, and lemurs. Opposable thumbs also evolved in giant pandas, but these are completely different in structure, having six fingers including the thumb, which develops from a wrist bone entirely separately from other fingers.

Primate phenotypes

Further information: Human skin color § Genetics of skin color variation

 

Convergent evolution in humans includes blue eye colour and light skin colour. When humans migrated out of Africa, they moved to more northern latitudes with less intense sunlight. It was beneficial to them to have reduced skin pigmentation. It appears certain that there was some lightening of skin colour before European and East Asian lineages diverged, as there are some skin-lightening genetic differences that are common to both groups. However, after the lineages diverged and became genetically isolated, the skin of both groups lightened more, and that additional lightening was due to different genetic changes.

Despite the similarity of appearance, the genetic basis of blue eyes is different in humans and lemurs.

Lemurs and humans are both primates. Ancestral primates had brown eyes, as most primates do today. The genetic basis of blue eyes in humans has been studied in detail and much is known about it. It is not the case that one gene locus is responsible, say with brown dominant to blue eye colour. However, a single locus is responsible for about 80% of the variation. In lemurs, the differences between blue and brown eyes are not completely known, but the same gene locus is not involved.

In plants

In myrmecochory, seeds such as those of Chelidonium majus have a hard coating and an attached oil body, an elaiosome, for dispersal by ants.

The annual life-cycle

While most plant species are perennial, about 6% follow an annual life cycle, living for only one growing season. The annual life cycle independently emerged in over 120 plant families of angiosperms. The prevalence of annual species increases under hot-dry summer conditions in the four species-rich families of annuals (Asteraceae, Brassicaceae, Fabaceae, and Poaceae), indicating that the annual life cycle is adaptive.

Carbon fixation

C₄ photosynthesis, one of the three major carbon-fixing biochemical processes, has arisen independently up to 40 times. About 7,600 plant species of angiosperms use C₄ carbon fixation, with many monocots including 46% of grasses such as maize and sugar cane, and dicots including several species in the Chenopodiaceae and the Amaranthaceae.

Fruits

Fruits with a wide variety of structural origins have converged to become edible. Apples are pomes with five carpels; their accessory tissues form the apple's core, surrounded by structures from outside the botanical fruit, the receptacle or hypanthium. Other edible fruits include other plant tissues; the fleshy part of a tomato is the walls of the pericarp. This implies convergent evolution under selective pressure, in this case the competition for seed dispersal by animals through consumption of fleshy fruits.

Seed dispersal by ants (myrmecochory) has evolved independently more than 100 times, and is present in more than 11,000 plant species. It is one of the most dramatic examples of convergent evolution in biology.

Carnivory

Molecular convergence in carnivorous plants

Carnivory has evolved multiple times independently in plants in widely separated groups. In three species studied, Cephalotus follicularis, Nepenthes alata and Sarracenia purpurea, there has been convergence at the molecular level. Carnivorous plants secrete enzymes into the digestive fluid they produce. By studying phosphatase, glycoside hydrolase, glucanase, RNAse and chitinase enzymes as well as a pathogenesis-related protein and a thaumatin-related protein, the authors found many convergent amino acid substitutions. These changes were not at the enzymes' catalytic sites, but rather on the exposed surfaces of the proteins, where they might interact with other components of the cell or the digestive fluid. The authors also found that homologous genes in the non-carnivorous plant Arabidopsis thaliana tend to have their expression increased when the plant is stressed, leading the authors to suggest that stress-responsive proteins have often been co-opted in the repeated evolution of carnivory.

Methods of inference

Angiosperm phylogeny of orders based on classification by the Angiosperm Phylogeny Group. The figure shows the number of inferred independent origins of C₃-C₄ photosynthesis and C₄ photosynthesis in parentheses.

Phylogenetic reconstruction and ancestral state reconstruction proceed by assuming that evolution has occurred without convergence. Convergent patterns may, however, appear at higher levels in a phylogenetic reconstruction, and are sometimes explicitly sought by investigators. The methods applied to infer convergent evolution depend on whether pattern-based or process-based convergence is expected. Pattern-based convergence is the broader term, for when two or more lineages independently evolve patterns of similar traits. Process-based convergence is when the convergence is due to similar forces of natural selection.

Pattern-based measures

Earlier methods for measuring convergence incorporate ratios of phenotypic and phylogenetic distance by simulating evolution with a Brownian motion model of trait evolution along a phylogeny. More recent methods also quantify the strength of convergence. One drawback to keep in mind is that these methods can confuse long-term stasis with convergence due to phenotypic similarities. Stasis occurs when there is little evolutionary change among taxa.

Distance-based measures assess the degree of similarity between lineages over time. Frequency-based measures assess the number of lineages that have evolved in a particular trait space.

Process-based measures

Methods to infer process-based convergence fit models of selection to a phylogeny and continuous trait data to determine whether the same selective forces have acted upon lineages. This uses the Ornstein–Uhlenbeck process to test different scenarios of selection. Other methods rely on an a priori specification of where shifts in selection have occurred.