Sexual reproduction

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Sexual_reproduction

In the first stage of sexual reproduction, meiosis, the number of chromosomes is reduced from a diploid number (2n) to a haploid number (n). During fertilisation, haploid gametes come together to form a diploid zygote, and the original number of chromosomes is restored.

Sexual reproduction is a type of reproduction that involves a complex life cycle in which a gamete (haploid reproductive cells, such as a sperm or egg cell) with a single set of chromosomes combines with another gamete to produce a zygote that develops into an organism composed of cells with two sets of chromosomes (diploid). This is typical in animals, though the number of chromosome sets and how that number changes in sexual reproduction varies, especially among plants, fungi, and other eukaryotes.

In placental mammals, the sperm cells exit from the urethra through the penis for males while the egg cells exit through the oviduct to the uterus for females. Other vertebrates of both sexes possess a cloaca for the release of sperm or egg cells.

Sexual reproduction is the most common life cycle in multicellular eukaryotes, such as animals, fungi and plants. Sexual reproduction also occurs in some unicellular eukaryotes. Sexual reproduction does not occur in prokaryotes, unicellular organisms without cell nuclei, such as bacteria and archaea. However, some processes in bacteria, including bacterial conjugation, transformation and transduction, may be considered analogous to sexual reproduction in that they incorporate new genetic information. Some proteins and other features that are key for sexual reproduction may have arisen in bacteria, but sexual reproduction is believed to have developed in an ancient eukaryotic ancestor.

In eukaryotes, diploid precursor cells divide to produce haploid cells in a process called meiosis. In meiosis, DNA is replicated to produce a total of four copies of each chromosome. This is followed by two cell divisions to generate haploid gametes. After the DNA is replicated in meiosis, the homologous chromosomes pair up so that their DNA sequences are aligned with each other. During this period before cell divisions, genetic information is exchanged between homologous chromosomes in genetic recombination. Homologous chromosomes contain highly similar but not identical information, and by exchanging similar but not identical regions, genetic recombination increases genetic diversity among future generations.

During sexual reproduction, two haploid gametes combine into one diploid cell known as a zygote in a process called fertilization. The nuclei from the gametes fuse, and each gamete contributes half of the genetic material of the zygote. Multiple cell divisions by mitosis (without change in the number of chromosomes) then develop into a multicellular diploid phase or generation. In plants, the diploid phase, known as the sporophyte, produces spores by meiosis. These spores then germinate and divide by mitosis to form a haploid multicellular phase, the gametophyte, which produces gametes directly by mitosis. This type of life cycle, involving alternation between two multicellular phases, the sexual haploid gametophyte and asexual diploid sporophyte, is known as alternation of generations.

The evolution of sexual reproduction is considered paradoxical, because asexual reproduction should be able to outperform it as every young organism created can bear its own young. This implies that an asexual population has an intrinsic capacity to grow more rapidly with each generation. This 50% cost is a fitness disadvantage of sexual reproduction. The two-fold cost of sex includes this cost and the fact that any organism can only pass on 50% of its own genes to its offspring. However, one definite advantage of sexual reproduction is that it increases genetic diversity and impedes the accumulation of harmful genetic mutations.

Sexual selection is a mode of natural selection in which some individuals out-reproduce others of a population because they are better at securing mates for sexual reproduction. It has been described as "a powerful evolutionary force that does not exist in asexual populations".

Evolution

Main article: Evolution of sexual reproduction

The first fossilized evidence of sexual reproduction in eukaryotes is from the Stenian period, about 1.05 billion years old.

Biologists studying evolution propose several explanations for the development of sexual reproduction and its maintenance. These reasons include reducing the likelihood of the accumulation of deleterious mutations, increasing rate of adaptation to changing environments, dealing with competition, DNA repair, masking deleterious mutations, and reducing genetic variation on the genomic level. All of these ideas about why sexual reproduction has been maintained are generally supported, but ultimately the size of the population determines if sexual reproduction is entirely beneficial. Larger populations appear to respond more quickly to some of the benefits obtained through sexual reproduction than do smaller population sizes.

However, newer models presented in recent years suggest a basic advantage for sexual reproduction in slowly reproducing complex organisms.

Sexual reproduction allows these species to exhibit characteristics that depend on the specific environment that they inhabit, and the particular survival strategies that they employ.

Sexual selection

Main article: Sexual selection

In order to reproduce sexually, both males and females need to find a mate. Generally in animals mate choice is made by females while males compete to be chosen. This can lead organisms to extreme efforts in order to reproduce, such as combat and display, or produce extreme features caused by a positive feedback known as a Fisherian runaway. Thus sexual reproduction, as a form of natural selection, has an effect on evolution. Sexual dimorphism is where the basic phenotypic traits vary between males and females of the same species. Dimorphism is found in both sex organs and in secondary sex characteristics, body size, physical strength and morphology, biological ornamentation, behavior and other bodily traits. However, sexual selection is only implied over an extended period of time leading to sexual dimorphism.

Animals

Further information: Reproductive system § Animals, Fertilisation § Fertilisation in animals, and Animal sexual behavior

Arthropods

Aphid giving birth to live young from an unfertilized egg

 

Harvestmen mating

A few arthropods, such as barnacles, are hermaphroditic, that is, each can have the organs of both sexes. However, individuals of most species remain of one sex their entire lives. A few species of insects and crustaceans can reproduce by parthenogenesis, especially if conditions favor a "population explosion". However, most arthropods rely on sexual reproduction, and parthenogenetic species often revert to sexual reproduction when conditions become less favorable. The ability to undergo meiosis is widespread among arthropods including both those that reproduce sexually and those that reproduce parthenogenetically. Although meiosis is a major characteristic of arthropods, understanding of its fundamental adaptive benefit has long been regarded as an unresolved problem, that appears to have remained unsettled.

Aquatic arthropods may breed by external fertilization, as for example horseshoe crabs do, or by internal fertilization, where the ova remain in the female's body and the sperm must somehow be inserted. All known terrestrial arthropods use internal fertilization. Opiliones (harvestmen), millipedes, and some crustaceans use modified appendages such as gonopods or penises to transfer the sperm directly to the female. However, most male terrestrial arthropods produce spermatophores, waterproof packets of sperm, which the females take into their bodies. A few such species rely on females to find spermatophores that have already been deposited on the ground, but in most cases males only deposit spermatophores when complex courtship rituals look likely to be successful.

The nauplius larva of a penaeid shrimp

Most arthropods lay eggs, but scorpions are ovoviviparous: they produce live young after the eggs have hatched inside the mother, and are noted for prolonged maternal care. Newly born arthropods have diverse forms, and insects alone cover the range of extremes. Some hatch as apparently miniature adults (direct development), and in some cases, such as silverfish, the hatchlings do not feed and may be helpless until after their first moult. Many insects hatch as grubs or caterpillars, which do not have segmented limbs or hardened cuticles, and metamorphose into adult forms by entering an inactive phase in which the larval tissues are broken down and re-used to build the adult body. Dragonfly larvae have the typical cuticles and jointed limbs of arthropods but are flightless water-breathers with extendable jaws. Crustaceans commonly hatch as tiny nauplius larvae that have only three segments and pairs of appendages.

Insects

Further information: Insect § Reproduction and development

An Australian emperor dragonfly laying eggs, guarded by a male

Insect species make up more than two-thirds of all extant animal species. Most insect species reproduce sexually, though some species are facultatively parthenogenetic. Many insect species have sexual dimorphism, while in others the sexes look nearly identical. Typically they have two sexes with males producing spermatozoa and females ova. The ova develop into eggs that have a covering called the chorion, which forms before internal fertilization. Insects have very diverse mating and reproductive strategies most often resulting in the male depositing a spermatophore within the female, which she stores until she is ready for egg fertilization. After fertilization, and the formation of a zygote, and varying degrees of development, in many species the eggs are deposited outside the female; while in others, they develop further within the female and the young are born live.

Mammals

Main article: Mammalian reproduction

See also: Human reproduction

 

Genitourinary system of a male and female cat

There are three extant kinds of mammals: monotremes, placentals and marsupials, all with internal fertilization. In placental mammals, offspring are born as juveniles: complete animals with the sex organs present although not reproductively functional. After several months or years, depending on the species, the sex organs develop further to maturity and the animal becomes sexually mature. Most female mammals are only fertile during certain periods during their estrous cycle, at which point they are ready to mate. Male mammals ejaculate semen through the penis into the female reproductive tract during copulation. For most mammals, males and females exchange sexual partners throughout their adult lives.

Fish

Further information: Fish § Reproductive system

The vast majority of fish species lay eggs that are then fertilized by the male. Some species lay their eggs on a substrate like a rock or on plants, while others scatter their eggs and the eggs are fertilized as they drift or sink in the water column.

Some fish species use internal fertilization and then disperse the developing eggs or give birth to live offspring. Fish that have live-bearing offspring include the guppy and mollies or Poecilia. Fishes that give birth to live young can be ovoviviparous, where the eggs are fertilized within the female and the eggs simply hatch within the female body, or in seahorses, the male carries the developing young within a pouch, and gives birth to live young. Fishes can also be viviparous, where the female supplies nourishment to the internally growing offspring. Some fish are hermaphrodites, where a single fish is both male and female and can produce eggs and sperm. In hermaphroditic fish, some are male and female at the same time while in other fish they are serially hermaphroditic; starting as one sex and changing to the other. In at least one hermaphroditic species, self-fertilization occurs when the eggs and sperm are released together. Internal self-fertilization may occur in some other species. One fish species does not reproduce by sexual reproduction but uses sex to produce offspring; Poecilia formosa is a unisex species that uses a form of parthenogenesis called gynogenesis, where unfertilized eggs develop into embryos that produce female offspring. Poecilia formosa mate with males of other fish species that use internal fertilization, the sperm does not fertilize the eggs but stimulates the growth of the eggs which develops into embryos.

Plants

Main article: Plant reproduction

Animals have life cycles with a single diploid multicellular phase that produces haploid gametes directly by meiosis. Male gametes are called sperm, and female gametes are called eggs or ova. In animals, fertilization of the ovum by a sperm results in the formation of a diploid zygote that develops by repeated mitotic divisions into a diploid adult. Plants have two multicellular life-cycle phases, resulting in an alternation of generations. Plant zygotes germinate and divide repeatedly by mitosis to produce a diploid multicellular organism known as the sporophyte. The mature sporophyte produces haploid spores by meiosis that germinate and divide by mitosis to form a multicellular gametophyte phase that produces gametes at maturity. The gametophytes of different groups of plants vary in size. Mosses and other pteridophytic plants may have gametophytes consisting of several million cells, while angiosperms have as few as three cells in each pollen grain.

Flowering plants

Flowers contain the sexual organs of flowering plants.

Flowering plants are the dominant plant form on land and they reproduce either sexually or asexually. Often their most distinctive feature is their reproductive organs, commonly called flowers. The anther produces pollen grains which contain the male gametophytes that produce sperm nuclei. For pollination to occur, pollen grains must attach to the stigma of the female reproductive structure (carpel), where the female gametophytes are located within ovules enclose within the ovary. After the pollen tube grows through the carpel's style, the sex cell nuclei from the pollen grain migrate into the ovule to fertilize the egg cell and endosperm nuclei within the female gametophyte in a process termed double fertilization. The resulting zygote develops into an embryo, while the triploid endosperm (one sperm cell plus two female cells) and female tissues of the ovule give rise to the surrounding tissues in the developing seed. The ovary, which produced the female gametophyte(s), then grows into a fruit, which surrounds the seed(s). Plants may either self-pollinate or cross-pollinate.

In 2013, flowers dating from the Cretaceous (100 million years before present) were found encased in amber, the oldest evidence of sexual reproduction in a flowering plant. Microscopic images showed tubes growing out of pollen and penetrating the flower's stigma. The pollen was sticky, suggesting it was carried by insects.

Ferns

Further information: Alternation of generations

Ferns produce large diploid sporophytes with rhizomes, roots and leaves. Fertile leaves produce sporangia that contain haploid spores. The spores are released and germinate to produce small, thin gametophytes that are typically heart shaped and green in color. The gametophyte prothalli, produce motile sperm in the antheridia and egg cells in archegonia on the same or different plants. After rains or when dew deposits a film of water, the motile sperm are splashed away from the antheridia, which are normally produced on the top side of the thallus, and swim in the film of water to the archegonia where they fertilize the egg. To promote out crossing or cross fertilization the sperm are released before the eggs are receptive of the sperm, making it more likely that the sperm will fertilize the eggs of different thallus. After fertilization, a zygote is formed which grows into a new sporophytic plant. The condition of having separate sporophyte and gametophyte plants is called alternation of generations.

Bryophytes

The bryophytes, which include liverworts, hornworts and mosses, reproduce both sexually and vegetatively. They are small plants found growing in moist locations and like ferns, have motile sperm with flagella and need water to facilitate sexual reproduction. These plants start as a haploid spore that grows into the dominant gametophyte form, which is a multicellular haploid body with leaf-like structures that photosynthesize. Haploid gametes are produced in antheridia (male) and archegonia (female) by mitosis. The sperm released from the antheridia respond to chemicals released by ripe archegonia and swim to them in a film of water and fertilize the egg cells thus producing a zygote. The zygote divides by mitotic division and grows into a multicellular, diploid sporophyte. The sporophyte produces spore capsules (sporangia), which are connected by stalks (setae) to the archegonia. The spore capsules produce spores by meiosis and when ripe the capsules burst open to release the spores. Bryophytes show considerable variation in their reproductive structures and the above is a basic outline. Also in some species each plant is one sex (dioicous) while other species produce both sexes on the same plant (monoicous).

Fungi

Main article: Mating in fungi

Further information: Fungus § Reproduction

Puffballs emitting spores

Fungi are classified by the methods of sexual reproduction they employ. The outcome of sexual reproduction most often is the production of resting spores that are used to survive inclement times and to spread. There are typically three phases in the sexual reproduction of fungi: plasmogamy, karyogamy and meiosis. The cytoplasm of two parent cells fuse during plasmogamy and the nuclei fuse during karyogamy. New haploid gametes are formed during meiosis and develop into spores. The adaptive basis for the maintenance of sexual reproduction in the Ascomycota and Basidiomycota (dikaryon) fungi was reviewed by Wallen and Perlin. They concluded that the most plausible reason for maintaining this capability is the benefit of repairing DNA damage, caused by a variety of stresses, through recombination that occurs during meiosis.

Bacteria and archaea

Three distinct processes in prokaryotes are regarded as similar to eukaryotic sex: bacterial transformation, which involves the incorporation of foreign DNA into the bacterial chromosome; bacterial conjugation, which is a transfer of plasmid DNA between bacteria, but the plasmids are rarely incorporated into the bacterial chromosome; and gene transfer and genetic exchange in archaea.

Bacterial transformation involves the recombination of genetic material and its function is mainly associated with DNA repair. Bacterial transformation is a complex process encoded by numerous bacterial genes, and is a bacterial adaptation for DNA transfer. This process occurs naturally in at least 40 bacterial species. For a bacterium to bind, take up, and recombine exogenous DNA into its chromosome, it must enter a special physiological state referred to as competence (see Natural competence). Sexual reproduction in early single-celled eukaryotes may have evolved from bacterial transformation, or from a similar process in archaea (see below).

On the other hand, bacterial conjugation is a type of direct transfer of DNA between two bacteria mediated by an external appendage called the conjugation pilus. Bacterial conjugation is controlled by plasmid genes that are adapted for spreading copies of the plasmid between bacteria. The infrequent integration of a plasmid into a host bacterial chromosome, and the subsequent transfer of a part of the host chromosome to another cell do not appear to be bacterial adaptations.

Exposure of hyperthermophilic archaeal Sulfolobus species to DNA damaging conditions induces cellular aggregation accompanied by high frequency genetic marker exchange Ajon et al. hypothesized that this cellular aggregation enhances species-specific DNA repair by homologous recombination. DNA transfer in Sulfolobus may be an early form of sexual interaction similar to the more well-studied bacterial transformation systems that also involve species-specific DNA transfer leading to homologous recombinational repair of DNA damage.

Paleogenetics

From Wikipedia, the free encyclopedia

Paleogenetics is the study of the past through the examination of preserved genetic material from the remains of ancient organisms. Emile Zuckerkandl and Linus Pauling introduced the term in 1963, long before the sequencing of DNA, in reference to the possible reconstruction of the corresponding polypeptide sequences of past organisms. The first sequence of ancient DNA, isolated from a museum specimen of the extinct quagga, was published in 1984 by a team led by Allan Wilson.

Paleogeneticists do not recreate actual organisms, but piece together ancient DNA sequences using various analytical methods. Fossils are "the only direct witnesses of extinct species and of evolutionary events" and finding DNA within those fossils exposes tremendously more information about these species, potentially their entire physiology and anatomy.

The most ancient DNA sequence to date was reported in February 2021, from the tooth of a Siberian mammoth frozen for over a million years.

Applications

Evolution

Similar sequences are often found along DNA (and the derived protein polypeptide chains) in different species. This similarity is directly linked to the sequence of the DNA (the genetic material of the organism). Due to the improbability of this being random chance, and its consistency too long to be attributed to convergence by natural selection, these similarities can be plausibly linked to the existence of a common ancestor with common genes. This allows DNA sequences to be compared between species. Comparing an ancient genetic sequence to later or modern ones can be used to determine ancestral relations, while comparing two modern genetic sequences can determine, within error, the time since their last common ancestor.

Human evolution

Using the thigh bone of a Neanderthal female, 63% of the Neanderthal genome was recovered and 3.7 billion bases of DNA were decoded. It showed that Homo neanderthalensis was the closest living relative of Homo sapiens, until the former lineage died out 30,000 years ago. The Neanderthal genome was shown to be within the range of variation of those of anatomically modern humans, although at the far periphery of that range of variation. Paleogenetic analysis also suggests that Neanderthals shared slightly more DNA with chimpanzees than homo sapiens. It was also found that Neanderthals were less genetically diverse than modern humans, which indicates that Homo neanderthalensis grew from a group composed of relatively few individuals. DNA sequences suggest that Homo sapiens first appeared between about 130,000 and 250,000 years ago in Africa.

Paleogenetics opens up many new possibilities for the study of hominid evolution and dispersion. By analyzing the genomes of hominid remains, their lineage can be traced back to from where they came, or from where they share a common ancestor. The Denisova hominid, a species of hominid found in Siberia from which DNA was able to be extracted, may show signs of having genes that are not found in any Neanderthal nor Homo sapiens genome, possibly representing a new lineage or species of hominid.

Evolution of culture

Looking at DNA can give insight into lifestyles of people of the past. Neandertal DNA shows that they lived in small temporary communities. DNA analysis can also show dietary restrictions and mutations, such as the fact that Homo neanderthalensis was lactose-intolerant.

Archaeology

Ancient disease

Studying DNA of the deceased also allows us to look at the medical history of the human species. By looking back we can discover when certain diseases first appeared and began to afflict humans.

Ötzi

The oldest case of Lyme disease was discovered in the genome on Ötzi the Iceman. Ötzi died around 3,300 B.C., and his remains were discovered frozen in the Eastern Alps in the early 1990s, and his genetic material was analyzed in the 2010s. Genetic remains of the bacterium that causes Lyme disease, Borrelia burgdorferi, were discovered in the body.

Domestication of animals

Not only can past humans be investigated through paleogenetics, but the organisms they had an effect on can also be examined. Through examination of the divergence found in domesticated species such as cattle and the archaeological record from their wild counterparts; the effect of domestication can be studied, which could tell us a lot about the behaviors of the cultures that domesticated them. The genetics of these animals also reveals traits not shown in the paleontological remains, such as certain clues as to the behavior, development, and maturation of these animals. The diversity in genes can also tell where the species were domesticated, and how these domesticates migrated from these locations elsewhere.

Challenges

Ancient remains usually contain only a small fraction of the original DNA of an organism. This is due to the degradation of DNA in dead tissue by biotic and abiotic decay. DNA preservation depends on a number of environmental characteristics, including temperature, humidity, oxygen and sunlight. Remains from regions with high heat and humidity typically contain less intact DNA than those from permafrost or caves, where remains may persist in cold, low oxygen conditions for several hundred thousand years. In addition, DNA degrades much more quickly following excavation of materials, and freshly excavated bone has a much higher chance of containing viable genetic material. After excavation, bone may also become contaminated with modern DNA (i.e. from contact with skin or unsterilized tools), which can create false-positive results.

Free radical damage to DNA

From Wikipedia, the free encyclopedia

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

 

See also: DNA damage (naturally occurring) and DNA repair

Free radical damage to DNA can occur as a result of exposure to ionizing radiation or to radiomimetic compounds. Damage to DNA as a result of free radical attack is called indirect DNA damage because the radicals formed can diffuse throughout the body and affect other organs. Malignant melanoma can be caused by indirect DNA damage because it is found in parts of the body not exposed to sunlight. DNA is vulnerable to radical attack because of the very labile hydrogens that can be abstracted and the prevalence of double bonds in the DNA bases that free radicals can easily add to.

Damage via radiation exposure

Radiolysis of intracellular water by ionizing radiation creates peroxides, which are relatively stable precursors to hydroxyl radicals. 60%–70% of cellular DNA damage is caused by hydroxyl radicals, yet hydroxyl radicals are so reactive that they can only diffuse one or two molecular diameters before reacting with cellular components. Thus, hydroxyl radicals must be formed immediately adjacent to nucleic acids in order to react. Radiolysis of water creates peroxides that can act as diffusable, latent forms of hydroxyl radicals. Some metal ions in the vicinity of DNA generate the hydroxyl radicals from peroxide.

H₂O + hν → H₂O⁺ + e⁻

H₂O + e⁻ → H₂O⁻

H₂O⁺ → H⁺ + OH·

H₂O⁻ → OH⁻ + H·

2 OH· →H₂O₂

Free radical damage to DNA is thought to cause mutations that may lead to some cancers.

The Fenton reaction

The Fenton reaction results in the creation of hydroxyl radicals from hydrogen peroxide and an Iron (II) catalyst. Iron(III) is regenerated via the Haber–Weiss reaction. Transition metals with a free coordination site are capable of reducing peroxides to hydroxyl radicals. Iron is believed to be the metal responsible for the creation of hydroxyl radicals because it exists at the highest concentration of any transition metal in most living organisms. The Fenton reaction is possible because transition metals can exist in more than one oxidation state and their valence electrons may be unpaired, allowing them to participate in one-electron redox reactions.

Fe²⁺ + H₂O₂ → Fe³⁺ + OH· + OH⁻

The creation of hydroxyl radicals by iron(II) catalysis is important because iron(II) can be found coordinated with, and therefore in close proximity to, DNA. This reaction allows for hydrogen peroxide created by radiolysis of water to diffuse to the nucleus and react with Iron (II) to produce hydroxyl radicals, which in turn react with DNA. The location and binding of Iron (II) to DNA may play an important role in determining the substrate and nature of the radical attack on the DNA. The Fenton reaction generates two types of oxidants, Type I and Type II. Type I oxidants are moderately sensitive to peroxides and ethanol. Type I and Type II oxidants preferentially cleave at the specific sequences.

Radical hydroxyl attack

Radical hydroxyl attacks can form baseless sites

Hydroxyl radicals can attack the deoxyribose DNA backbone and bases, potentially causing a plethora of lesions that can be cytotoxic or mutagenic. Cells have developed complex and efficient repair mechanisms to fix the lesions. In the case of free radical attack on DNA, base-excision repair is the repair mechanism used. Hydroxyl radical reactions with the deoxyribose sugar backbone are initiated by hydrogen abstraction from a deoxyribose carbon, and the predominant consequence is eventual strand breakage and base release. The hydroxyl radical reacts with the various hydrogen atoms of the deoxyribose in the order 5′ H > 4′ H > 3′ H ≈ 2′ H ≈ 1′ H. This order of reactivity parallels the exposure to solvent of the deoxyribose hydrogens.

Hydroxyl radicals react with DNA bases via addition to the electron-rich, pi bonds. These pi bonds in the bases are located between C5-C6 of pyrimidines and N7-C8 in purines. Upon addition of the hydroxyl radical, many stable products can be formed. In general, radical hydroxyl attacks on base moieties do not cause altered sugars or strand breaks except when the modifications labilize the N-glycosyl bond, allowing the formation of baseless sites that are subject to beta-elimination.

Abasic sites

Route of deoxyribonolactone formation

Hydrogen abstraction from the 1’-deoxyribose carbon by the hydroxyl radical creates a 1 ‘-deoxyribosyl radical. The radical can then react with molecular oxygen, creating a peroxyl radical which can be reduced and dehydrated to yield a 2’-deoxyribonolactone and free base. A deoxyribonolactone is mutagenic and resistant to repair enzymes. Thus, an abasic site is created.

Radical damage through radiomimetic compounds

Radical damage to DNA can also occur through the interaction of DNA with certain natural products known as radiomimetic compounds, molecular compounds which affect DNA in similar ways to radiation exposure. Radiomimetic compounds induce double-strand breaks in DNA via highly specific, concerted free-radical attacks on the deoxyribose moieties in both strands of DNA.

General mechanism

Many radiomimetic compounds are enediynes, which undergo the Bergman cyclization reaction to produce a 1,4-didehydrobenzene diradical. The 1,4-didehydrobenzene diradical is highly reactive, and will abstract hydrogens from any possible hydrogen-donor.

In the presence of DNA, the 1,4-didehydrobenzene diradical abstracts hydrogens from the deoxyribose sugar backbone, predominantly at the C-1’, C-4’ and C-5’ positions. Hydrogen abstraction causes radical formation at the reacted carbon. The carbon radical reacts with molecular oxygen, which leads to a strand break in the DNA through a variety of mechanisms. 1,4-Didehydrobenzene is able to position itself in such a way that it can abstract proximal hydrogens from both strands of DNA. This produces a double-strand break in the DNA, which can lead to cellular apoptosis if not repaired.

Enediynes generally undergo the Bergman cyclization at temperatures exceeding 200 °C. However, incorporating the enediyne into a 10-membered cyclic hydrocarbon makes the reaction more thermodynamically favorable by releasing the ring strain of the reactants. This allows for the Bergman cyclization to occur at 37 °C, the biological temperature of humans. Molecules which incorporate enediynes into these larger ring structures have been found to be extremely cytotoxic.

Natural products

Enediynes are present in many complicated natural products. They were originally discovered in the early 1980s during a search for new anticancer products produced by microorganisms. Calicheamicin was one of the first such products identified and was originally found in a soil sample taken from Kerrville, Texas. These compounds are synthesized by bacteria as defense mechanisms due to their ability to cleave DNA through the formation of 1,4-didehydrobenzene from the enediyne component of the molecule.

Calicheamicin and other related compounds share several common characteristics. The extended structures attached to the enediyne allow the compound to specifically bind DNA, in most cases to the minor groove of the double helix. Additionally, part of the molecule is known as the “trigger” which, under specific physiological conditions, activates the enediyne, known as the “warhead” and 1,4-didehydrobenzene is generated.

Three classes of enediynes have since been identified: calicheamicin, dynemicin, and chromoprotein-based products.

The calicheamicin types are defined by a methyl trisulfide group that is involved in triggering the molecule by the following mechanism.

Calicheamicin and the closely related esperamicin have been used as anticancer drugs due to their high toxicity and specificity.

Dynemicin and its relatives are characterized by the presence of an anthraquinone and enediyne core. The anthraquinone component allows for specific binding of DNA at the 3’ side of purine bases through intercalation, a site that is different from calicheamicin. Its ability to cleave DNA is greatly increased in the presence of NADPH and thiol compounds. This compound has also found prominence as an antitumor agent.

Chromoprotein enediynes are characterized by an unstable chromophore enediyne bound to an apoprotein.

The chromophore is unreactive when bound to the apoprotein. Upon its release, it reacts to form 1,4-didehydrobenzene and subsequently cleaves DNA.

Antitumor ability

Most enediynes, including the ones listed above, have been used as potent antitumor antibiotics due to their ability to efficiently cleave DNA. Calicheamicin and esperamicin are the two most commonly used types due to their high specificity when binding to DNA, which minimizes unfavorable side reactions. They have been shown to be especially useful for treating acute myeloid leukemia.

Additionally, calicheamicin is able to cleave DNA at low concentrations, proving to be up to 1000 times more effective than adriamycin at combating certain types of tumors.

The free radical mechanism to treat certain types of cancers extends beyond enediynes. Tirapazamine generates a free radical under anoxic conditions instead of the trigger mechanism of an enediyne. The free radical then continues on to cleave DNA in a similar manner to 1,4-didehydrobenzene in order to treat cancerous cells. It is currently in Phase III trials.

Evolution of Meiosis

Meiosis is a central feature of sexual reproduction in eukaryotes. The need to repair oxidative DNA damage caused by oxidative free radicals has been hypothesized to be a major driving force in the evolution of meiosis.

Jeanne Calment

From Wikipedia, the free encyclopedia

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

 

Jeanne Calment
Calment in 1915, aged 40

Jeanne Louise Calment (French: [ʒan lwiz kalmɑ̃] ^ⓘ; 21 February 1875 – 4 August 1997) was a French supercentenarian and, with a documented lifespan of 122 years and 164 days, the oldest person ever whose age has been verified. Her longevity attracted media attention and medical studies of her health and lifestyle. She is the only person verified to have reached the age of 120 and beyond.

According to census records, Calment outlived both her daughter and grandson. In January 1988, she was widely reported to be the oldest living person, and in 1995, at age 120, was declared the oldest verified person to have ever lived.

Early life

Birth certificate of Jeanne Calment

Calment was born on 21 February 1875 in Arles, Bouches-du-Rhône, Provence. Some of her close family members also had an above-average lifespan as her older brother, François (1865–1962), lived to the age of 97, her father, Nicolas (1837–1931), who was a shipbuilder, 93, and her mother, Marguerite Gilles (1838–1924), who was from a family of millers, 86.

From the age of seven until her first Communion, she attended Mrs. Benet's church primary school in Arles, and then the local collège (secondary school), finishing at 16 with the brevet classique diploma. Asked about her daily routine while at primary school, she replied that "when you are young, you get up at eight o'clock". In lieu of a solid breakfast, she would have either coffee with milk, or hot chocolate, and at noon her father would pick her up from school to have lunch at home before she returned to school for the afternoon. In the following years, she continued to live with her parents, awaiting marriage, painting, and improving her piano skills.

Adult life

Calment at age 20 in 1895

On 8 April 1896, at the age of 21, Jeanne married her double second cousin, Fernand Nicolas Calment (1868–1942). Their paternal grandfathers were brothers, and their paternal grandmothers were sisters. He had reportedly started courting her when she was 15, but Jeanne was "too young to be interested in boys". Fernand was heir to a drapery business located in a classic Provençal-style building in the centre of Arles, and the couple moved into a spacious apartment above the family store. Jeanne employed servants and never had to work; she led a leisurely lifestyle within the upper society of Arles, pursuing hobbies such as fencing, cycling, tennis, swimming, rollerskating, playing the piano, and making music with friends. In the summer, the couple would stay at Uriage for mountaineering on the glacier. They also went hunting for rabbits and wild boars in the hills of Provence, using an "18mm rifle". Calment said she disliked shooting birds. She gave birth to her only child, a daughter named Yvonne Marie Nicolle Calment, on 19 January 1898. Yvonne married army officer Joseph Billot on 3 February 1926, and their only son, Frédéric, was born on 23 December of the same year. At the outbreak of World War I, Jeanne's husband Fernand, who was 46, was deemed too old to serve in the military.

Yvonne died of pleurisy on 19 January 1934, her 36th birthday, after which Calment raised Frédéric, although he lived with his father in the neighbouring apartment. World War II had little effect on Jeanne's life. She said that German soldiers slept in her rooms but "did not take anything away", so that she bore no grudge against them. In 1942, her husband Fernand died, aged 73, reportedly of cherry poisoning. By the 1954 census, she was still registered in the same apartment, together with her son-in-law, retired Colonel Billot, Yvonne's widower; the census documents list Jeanne as "mother" in 1954 and "widow" in 1962. Her grandson Frédéric Billot lived next door with his wife Renée. Her brother François died in 1962, aged 97. Her son-in-law Joseph died in January 1963, and her grandson Frédéric died in an automobile accident in August of the same year.

In 1965, aged 90 and with no heirs left, Calment signed a life estate contract on her apartment with civil law notary André-François Raffray, selling the property in exchange for a right of occupancy and a monthly revenue of 2,500 francs (€380) until her death. Raffray died on 25 December 1995, by which time Calment had received more than double the apartment's value from him, and his family had to continue making payments. She commented on the situation by saying, "in life, one sometimes makes bad deals". In 1985, she moved into a nursing home, having lived on her own until age 110. A documentary film about her life, entitled Beyond 120 Years with Jeanne Calment, was released in 1995. In 1996, Time's Mistress, a four-track CD of Jeanne speaking over musical backing tracks in various styles, including rap, was released.

Oldest documented human

Longevity records

In 1986, Calment became the oldest living person in France at the age of 111. Her profile increased during the centennial of Vincent van Gogh's move to Arles, which occurred from February 1888 to April 1889 when she was 13 and 14 years old. Calment claimed to reporters that she had met van Gogh at that time, introduced to him by her future husband in her uncle's fabric shop. She remembered that van Gogh gave her a condescending look, as if unimpressed by her. She described his personality as ugly, ungracious, and "very disagreeable", adding that he "reeked of alcohol". Calment said that she forgave van Gogh for his bad manners.

She was recognised by The Guinness Book of Records as the world's oldest living person in 1988, when she was 112. However, the Gerontology Research Group has since then validated the age of Easter Wiggins (1 June 1874 - 7 July 1990), meaning that in reality Calment became the world's oldest living person in 1990. At the age of 114, she briefly appeared in the 1990 fantasy film Vincent and Me, walking outside and answering questions.

Her status further increased when Guinness named her the oldest person ever on 17 October 1995. This was based on her surpassing the now-debunked age claim of Japanese man Shigechiyo Izumi. As a result of Izumi’s validation being withdrawn, Calment had already been the oldest person ever since surpassing the age of Easter Wiggins on 30 March 1991. Far exceeding any other verified human lifespan, Calment is widely reckoned as the best-documented supercentenarian recorded. For example, she was listed in fourteen census records, beginning in 1876 as a one-year-old infant. After Calment's death, at 122 years and 164 days, then almost 117-year-old Canadian woman Marie-Louise Meilleur became the oldest validated living person. Several claims to have surpassed Calment's age were made, but none have ever been proven. For about three decades, Calment has held the status of the oldest human being whose age has been validated by modern standards.

Age verification

In 1994, the city of Arles inquired about Calment's personal documents, in order to contribute to the city archives. However, reportedly on Calment's instructions, her documents and family photographs were selectively burned by a distant family member, Josette Bigonnet, a cousin of her grandson. The verification of her age began in 1995 when she turned 120, and was conducted over a full year. She was asked questions about documented details concerning relatives, and about people and places from her early life, for instance teachers or maids. A great deal of emphasis was put on a series of documents from population censuses, in which Calment was named from 1876 to 1975. The family's membership in the local Catholic bourgeoisie helped researchers find corroborating chains of documentary evidence. Calment's father had been a member of the city council, and her husband owned a large drapery and clothing business. The family lived in two apartments located in the same building as the store, one for Calment, her husband and his mother, one for their daughter Yvonne, her husband and their child. Several house servants were registered in the premises as well.

Popular media reports

Apocryphal media articles reported varying details, some of them unlikely. One report claimed that Calment recalled selling coloured pencils to van Gogh, and seeing the Eiffel Tower being built. Another wrote that she started fencing in 1960, aged 85. Calment reportedly ascribed her longevity and relatively youthful appearance for her age to a diet rich in olive oil.

Scepticism regarding age

Daughter Yvonne Calment in front of the Church of St. Trophime in Arles, 1920. This photograph was often mislabelled as depicting Jeanne at age 22.

Demographers have highlighted that Calment's age is an outlier, her lifespan being several years longer than the next oldest people ever documented, where the differences are usually by months or weeks. There have been various speculations about the authenticity of her age. In 2018, Russian gerontologist Valery Novoselov and mathematician Nikolay Zak revived the hypothesis that Jeanne died in 1934 and her daughter Yvonne, born in 1898, assumed her mother's official identity and was therefore 99 years old when she died in 1997; however, Zak had difficulty getting published. A Russian scientific journal found his paper too informal, as did the bioRxiv preprint repository, which led Zak to choose ResearchGate, a social networking site for scientists and researchers. The paper was accepted for publication in January 2019 in the peer-reviewed journal Rejuvenation Research, a month after a series of related posts by gerontology blogger Yuri Deigin, titled "J'Accuse!", had gone viral on Medium. This hypothesis is considered weak by mainstream longevity experts, such as French gerontologist Jean-Marie Robine.

Robine, one of two validators of Calment, dismissed the claims and pointed out that, during his research, Calment had correctly answered questions about things that her daughter could not have known first-hand. Robine also dismissed the idea that the residents of Arles could have been duped by the switch. Michel Allard, the second doctor who helped verify Calment's records, said that the team had considered the identity-switch hypothesis while Calment was still alive because she looked younger than her daughter in photographs, but similar discrepancies in the rates of aging are commonly found in families with centenarian members. Allard and Robine also mentioned the existence of numerous documents relating to Calment's activities throughout her life, and that Novoselov and Zak brought no evidence forward to support their hypothesis.

After a meeting of the National Institute for Demographic Studies (INED) in Paris on 23 January 2019, French, Swiss, and Belgian longevity experts commented that Novoselov and Zak had not provided any proof of an identity substitution, and they also announced that further research would be launched. After consulting several experts, The Washington Post wrote that "statistically improbable is not the same thing as statistically impossible", that Novoselov and Zak's claims are generally dismissed by the overwhelming majority of experts, and found them "lacking, if not outright deficient". In September 2019, several French scientists, including Robine and Allard, released a paper in The Journals of Gerontology where they contest the various claims made by Zak and his colleagues and mention various inaccuracies in the paper. The team presented evidence to support Calment's age – including multiple official documents, census data, and photographic evidence – and also argued that it was indeed statistically possible to reach Calment's age. The authors criticised the advocates of the identity switch hypothesis, and called for a retraction of Zak's article.

In February 2020, Zak and Philip Gibbs published an assessment applying Bayes' theorem to the question of her authenticity, noting that, while being subjective, it gave "a 99.99% chance of an identity switch in the case of Mme Calment". François Robin-Champigneul and Robert Young commented on Zak's and Gibbs' findings, with Robin-Champigneul saying that it "appears to be in fact a subjective and nonrigorous analysis", and Young saying that "[i]gnoring the actual facts of the case and stringing together opinions in a 'Bayesian' analysis are to merely misuse a mathematical tool". Young said to have found that "a very solid case that Jeanne was 122 years has already been made" but that biosampling still was needed to test "for biomarkers of extraordinary longevity". Robin-Champigneul stated that "the hypothesis of an identity swap with her daughter appears not even realistic given the context and the facts, and not supported by evidence".

Geneticists have noted that, since Jeanne Calment had 16 distinct great-great-grandparents (while her daughter Yvonne had only 12), the question of identity could easily be settled by a test for autozygous DNA, if a blood or tissue sample were to be made available.

Health and lifestyle

Calment's health presaged her later record. On television she stated "J'ai jamais été malade, jamais, jamais" (transl. I have never been ill, never ever). At age 20, incipient cataracts were discovered when she suffered a major episode of conjunctivitis. She married at 21, and her husband's wealth allowed her to live without working. All her life she took care of her skin with olive oil and a puff of powder. At an unspecified time in her youth, she had suffered from migraines. Her husband introduced her to smoking, offering cigarettes after meals, but she did not smoke outside these post-meal occasions. Calment continued smoking in her elderly years until she was 117. At "retirement age", she broke her ankle, but before that had never suffered any major injuries. She continued cycling until her hundredth birthday. Around age 100, she fractured her leg, but she recovered quickly and was able to walk again.

After her brother, her son-in-law and her grandson died in 1962–63, Calment had no remaining family members. She lived on her own from age 88 until shortly before her 110th birthday, when she decided to move to a nursing home. Her move was precipitated by the winter of 1985 which froze the water pipes in her house (she never used heating in the winter) and caused frostbite to her hands.

Daily routine

After her admission to the Maison du Lac nursing home in January 1985, aged almost 110, Calment initially followed a highly ritualised daily routine. She requested to be awoken at 6:45 a.m., and started the day with a long prayer at her window, thanking God for being alive and for the beautiful day which was starting. She sometimes loudly asked the reason for her longevity and why she was the only one to be still alive in her family. Seated on her armchair, she did gymnastics wearing her stereo headset. Her exercises included flexing and extending the hands, then the legs. Nurses noted that she moved faster than other residents who were 30 years younger. Her breakfast consisted of coffee with milk and rusks.

She washed herself unassisted with a flannel cloth rather than taking a shower, applying first soap, then olive oil and powder to her face. She washed her own glass and cutlery before proceeding to lunch. She enjoyed daube (braised beef), but was not keen on boiled fish. She had dessert with every meal, and said that given a choice she would eat fried and spicy foods instead of the bland foods on the menu. She made herself daily fruit salads with bananas and oranges. She enjoyed chocolate, sometimes indulging in a kilogram (2.2 lb) per week. After the meal, she smoked a cigarette and drank a small amount of port wine. In the afternoon, she would take a nap for two hours in her armchair, and then visit her neighbours in the care home, telling them about the latest news she had heard on the radio. At nightfall, she would dine quickly, return to her room, listen to music (her poor eyesight preventing her from enjoying her crosswords pastime), smoke a last cigarette and go to bed at 10:00 p.m. On Sundays, she went to Mass, and on Fridays she went to Vespers and regularly prayed to and sought help from God and wondered about the afterlife.

Medical follow-up

Medical student Georges Garoyan published a thesis on Calment when she was 114 years old in January 1990. The first part records her daily routine, and the second presents her medical history. She stated that she had been vaccinated as a child but could not remember which vaccine(s). Apart from aspirin against migraines she had never taken any medicine, not even herbal teas. She did not contract German measles, chickenpox, or urinary infections, and was not prone to hypertension or diabetes. In April 1986, aged 111, she was sent to a hospital for heart failure and treated with digoxin. Later she suffered from arthropathy in the ankles, elbows, and wrists, which was successfully treated with anti-inflammatory medication. Her arterial blood pressure was 140mm/70mm, her pulse 84/min. Her height was 150 cm (4 ft 11 in), and her weight 45 kg (99 lb), showing little variation from previous years. She scored well on mental tests, except on numeric tasks and recall of recent events.

Analyses of her blood samples were in normal ranges between ages 111–114, with no signs of dehydration, anemia, chronic infection or renal impairment. Genetic analysis of the HLA system revealed the presence of the DR1 allele, common among centenarians. A cardiological assessment revealed a moderate left ventricular hypertrophy with a mild left atrial dilatation and extrasystolic arrhythmia. Radiology revealed diffuse osteoporosis, as well as incipient osteoarthritis in the right hip. An ultrasound exam showed no anomalies of internal organs. At this stage, Calment was still in good health, and continued to walk without a cane. She fell in January 1990 (aged almost 115) and fractured her femur, which required surgery. Subsequently, Calment used a wheelchair, and she abandoned her daily routine.

At the age of 115, Calment attracted the attention of researchers Jean-Marie Robine and Michel Allard, who collaborated with her attending doctor, Victor Lèbre, to interview her, verify her age and identify factors promoting her longevity. According to their year-long analysis, Calment's vision was severely impaired by bilateral cataracts, yet she refused to undergo a routine operation to restore her eyesight; she had a moderately weak heart, a chronic cough, and bouts of rheumatism. On the other hand, her digestion was always good, she slept well, and did not have incontinence. During the last years, she was 137 cm (4 ft 6 in) tall, and weighed 40 kg (88 lb); she confirmed that she had always been small, and had lost weight in recent years. Her eyes were light grey, and her white hair had once been chestnut brown.

At the age of 118, she was submitted to repeated neurophysiological tests and a CT scan. The tests showed that her verbal memory and language fluency were comparable to those of persons with the same level of education in their eighties and nineties. Frontal brain lobe functions were relatively spared from deterioration, and there was no evidence of progressive neurological disease, depressive symptoms or other functional illness. Her cognitive functioning was observed to improve slightly over the six-month period. Calment reportedly remained "mentally sharp" until the end of her life.

Death

Calment died of unspecified causes on 4 August 1997 around 10:00 a.m in her home town of Arles, France. She was 122 years and 164 days old. The New York Times quoted Robine as stating that she had been in good health, though almost blind and deaf, as little as a month before her death.

Francophonie

From Wikipedia, the free encyclopedia

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

Geographic distribution of the French language:

  Majority native language

  Official but not majority native language

  Administrative or cultural language

Map showing the member states of the Organisation internationale de la Francophonie (in blue and green). This map does not exactly represent the francophone space, as it is a political organisation.

Proportion of French-speakers (including L2-speakers) by country in 2022 according to the OIF

  1–9% francophone

  10–19% francophone

  20–29% francophone

  30–39% francophone

  40–49% francophone

  50%+ francophone

The Francophonie or Francophone world is the whole body of people and organisations around the world who use the French language regularly for private or public purposes. The term was coined by Onésime Reclus in 1880 and became important as part of the conceptual rethinking of cultures and geography in the late 20th century.

When used to refer to the French-speaking world, the Francophonie encompasses the countries and territories where French is official or serves as an administrative or major secondary language, which spans 50 countries and dependencies across all inhabited continents. The vast majority of these are also member states of the Organisation internationale de la Francophonie (OIF), a body uniting countries where French is spoken and taught. Between 300 to 500 million people speak French as a first or secondary language, making it the second most geographically widespread language in the world after English.

Denominations

Francophonie, francophonie and francophone space are syntagmatic. This expression is relevant to countries which speak French as their national language, may it be as a mother language or a secondary language.

These expressions are sometimes misunderstood or misused by English speakers. They can be synonymous but most of the time they are complementary.

• "francophonie", with a small "f", refers to populations and people who speak French for communication or/and in their daily lives.
• "Francophonie", with a capital "F", can be defined as referring to the governments, governmental and non-governmental organisations or governing officials that share the use of French in their work and exchange.
• "Francophone space", "Francophone world", "Francosphere" represents not only a linguistic or geographic reality, but also a cultural entity: for example describing any individual who identifies with one of the francophone cultures, may it be Slavic, Latin, Creole, North American or Oceanian for example.

Origins

The term francophonie was invented by Onésime Reclus in 1880: "We also put aside four large countries, Senegal, Gabon, Cochinchina and Cambodia, whose future from a "Francophone" point of view is still very doubtful, except perhaps for Senegal" (in French « Nous mettons aussi de côté quatre grands pays, le Sénégal, le Gabon, la Cochinchine, le Cambodge dont l’avenir au point de vue « francophone » est encore très douteux sauf peut-être pour le Sénégal »); and then used by geographers.

During the Third Republic, the French language progressively gained importance.

The Académie française, a French institution created in 1635 in charge of officially determining and unifying the rules and evolutions of the French language, participated in the promotion and the development of the French language.

Countries

Main article: List of countries where French is an official language

The definition of the Francophone world is distinguished by countries and territories where French is an official language, those where it is the native language of the majority of the population, and those where the language is used as a working language of administration or where the language still has an important cultural impact and prestige. There are 50 countries and territories which fall into this category, although in some countries the Francosphere is limited to certain regions or states.

Being merely a member state of the OIF does not automatically make a country or territory "francophone" in the sense of the language having a major role in its society, be it as a working language or a strong cultural heritage to the French language. This is in part due to the OIF increasingly admitting new members based on loose criteria such as "significant second language learning" of French or parties interested in furthering the organisation's promotion of human rights, democracy, international cooperation, sustainable development, cultural and linguistic diversity, and education and training. Therefore, member states such as Romania, Egypt, and Armenia which have minimal to no connection with the French language and culture should not be considered as part of the Francophone world.