Genetic history of indigenous peoples of the Americas

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The genetic history of Indigenous peoples of the Americas (also named Amerindians or Amerinds in physical anthropology) is divided into two sharply distinct episodes: the initial peopling of the Americas during about 20,000 to 14,000 years ago (20–14 kya), and European contact, after about 500 years ago. The former is the determinant factor for the number of genetic lineages, zygosity mutations and founding haplotypes present in today's Indigenous Amerindian populations.

Most amerindian groups are derived from two ancestral lineages, which formed in Siberia prior to the Last Glacial Maximum, between about 36,000 and 25,000 years ago, East Eurasian and Ancient North Eurasian. They later dispersed throughout the Americas after about 16,000 years ago (an exception are the Na Dene and Eskimo–Aleut speaking groups, which are partially derived from Siberian populations which entered the Americas at a later time).

In the early 2000s, archaeogenetics was primarily based on human Y-chromosome DNA haplogroups and human mitochondrial DNA haplogroups. Autosomal "atDNA" markers are also used, but differ from mtDNA or Y-DNA in that they overlap significantly.

Analyses of genetics among Amerindian and Siberian populations have been used to argue for early isolation of founding populations on Beringia and for later, more rapid migration from Siberia through Beringia into the New World. The microsatellite diversity and distributions of the Y lineage specific to South America indicates that certain Amerindian populations have been isolated since the initial peopling of the region. The Na-Dené, Inuit and Indigenous Alaskan populations exhibit Haplogroup Q-M242; however, they are distinct from other indigenous Amerindians with various mtDNA and atDNA mutations. This suggests that the peoples who first settled in the northern extremes of North America and Greenland derived from later migrant populations than those who penetrated farther south in the Americas. Linguists and biologists have reached a similar conclusion based on analysis of Amerindian language groups and ABO blood group system distributions.

Autosomal DNA

Genetic diversity and population structure in the American landmass is also measured using autosomal (atDNA) micro-satellite markers genotyped; sampled from North, Central, and South America and analyzed against similar data available from other indigenous populations worldwide. The Amerindian populations show a lower genetic diversity than populations from other continental regions. Observed is a decreasing genetic diversity as geographic distance from the Bering Strait occurs, as well as a decreasing genetic similarity to Siberian populations from Alaska (the genetic entry point). Also observed is evidence of a higher level of diversity and lower level of population structure in western South America compared to eastern South America. There is a relative lack of differentiation between Mesoamerican and Andean populations, a scenario that implies that coastal routes were easier for migrating peoples (more genetic contributors) to traverse in comparison with inland routes.

The over-all pattern that is emerging suggests that the Americas were colonized by a small number of individuals (effective size of about 70), which grew by many orders of magnitude over 800 – 1000 years. The data also shows that there have been genetic exchanges between Asia, the Arctic, and Greenland since the initial peopling of the Americas.

Moreno-Mayar et al. (2018) have identified a basal Ancestral Native American (ANA) lineage. This lineage formed by admixture of early East Asian and Ancient North Eurasian lineages prior to the Last Glacial Maximum, ca. 36–25 kya. Basal ANA diverged into an "Ancient Beringian" (AB) lineage at ca. 20 kya. The non-AB lineage further diverged into "Northern Native American" (NNA) and "Southern Native American" (SNA) lineages between about 17.5 and 14.6 kya. Most pre-Columbian lineages are derived from NNA and SNA, except for the American Arctic, where there is evidence of later (after 10kya) admixture from Paleo-Siberian lineages.

In 2014, the autosomal DNA of a 12,500+-year-old infant from Montana was sequenced. The DNA was taken from a skeleton referred to as Anzick-1, found in close association with several Clovis artifacts. Comparisons showed strong affinities with DNA from Siberian sites, and virtually ruled out that particular individual had any close affinity with European sources (the "Solutrean hypothesis"). The DNA also showed strong affinities with all existing Amerindian populations, which indicated that all of them derive from an ancient population that lived in or near Siberia, the Upper Palaeolithic Mal'ta population.

According to an autosomal genetic study from 2012, Native Americans descend from at least three main migrant waves from East Asia. Most of it is traced back to a single ancestral population, called 'First Americans'. However, those who speak Inuit languages from the Arctic inherited almost half of their ancestry from a second East Asian migrant wave. And those who speak Na-dene, on the other hand, inherited a tenth of their ancestry from a third migrant wave. The initial settling of the Americas was followed by a rapid expansion southwards, by the coast, with little gene flow later, especially in South America. One exception to this are the Chibcha speakers, whose ancestry comes from both North and South America. 

Linguistic studies have backed up genetic studies, with ancient patterns having been found between the languages spoken in Siberia and those spoken in the Americas.

Two 2015 autosomal DNA genetic studies confirmed the Siberian origins of the Natives of the Americas. However an ancient signal of shared ancestry with Australasians (Natives of Australia, Melanesia and the Andaman Islands) was detected among the Natives of the Amazon region. The migration coming out of Siberia would have happened 23,000 years ago.

Paternal lineages

Further information on individual Amerindian groups by Y-DNA: Y-DNA haplogroups in indigenous peoples of the Americas

A "Central Siberian" origin has been postulated for the paternal lineage of the source populations of the original migration into the Americas.

Membership in haplogroups Q and C3b implies indigenous American patrilineal descent.

The micro-satellite diversity and distribution of a Y lineage specific to South America suggest that certain Amerindian populations became isolated after the initial colonization of their regions. The Na-Dené, Inuit and Indigenous Alaskan populations exhibit haplogroup Q (Y-DNA) mutations, but are distinct from other indigenous Amerindians with various mtDNA and autosomal DNA (atDNA) mutations. This suggests that the earliest migrants into the northern extremes of North America and Greenland derived from later migrant populations.

Haplogroup Q

Q-M242 (mutational name) is the defining (SNP) of Haplogroup Q (Y-DNA) (phylogenetic name). In Eurasia, haplogroup Q is found among indigenous Siberian populations, such as the modern Chukchi and Koryak peoples. In particular, two groups exhibit large concentrations of the Q-M242 mutation, the Ket (93.8%) and the Selkup (66.4%) peoples. The Ket are thought to be the only survivors of ancient wanderers living in Siberia. Their population size is very small; there are fewer than 1,500 Ket in Russia. The Selkup have a slightly larger population size than the Ket, with approximately 4,250 individuals.

Starting the Paleo-Indians period, a migration to the Americas across the Bering Strait (Beringia) by a small population carrying the Q-M242 mutation took place. A member of this initial population underwent a mutation, which defines its descendant population, known by the Q-M3 (SNP) mutation. These descendants migrated all over the Americas.

Haplogroup Q-M3 is defined by the presence of the rs3894 (M3) (SNP). The Q-M3 mutation is roughly 15,000 years old as that is when the initial migration of Paleo-Indians into the Americas occurred. Q-M3 is the predominant haplotype in the Americas, at a rate of 83% in South American populations, 50% in the Na-Dené populations, and in North American Eskimo-Aleut populations at about 46%. With minimal back-migration of Q-M3 in Eurasia, the mutation likely evolved in east-Beringia, or more specifically the Seward Peninsula or western Alaskan interior. The Beringia land mass began submerging, cutting off land routes.

Since the discovery of Q-M3, several subclades of M3-bearing populations have been discovered. An example is in South America, where some populations have a high prevalence of (SNP) M19, which defines subclade Q-M19. M19 has been detected in (59%) of Amazonian Ticuna men and in (10%) of Wayuu men. Subclade M19 appears to be unique to South American Indigenous peoples, arising 5,000 to 10,000 years ago. This suggests that population isolation, and perhaps even the establishment of tribal groups, began soon after migration into the South American areas. Other American subclades include Q-L54, Q-Z780, Q-MEH2, Q-SA01, and Q-M346 lineages. In Canada, two other lineages have been found. These are Q-P89.1 and Q-NWT01.

Haplogroup R1

Haplogroup R1 (Y-DNA) is the second most predominant Y haplotype found among indigenous Amerindians after Q (Y-DNA). The distribution of R1 is believed by some to be associated with the re-settlement of Eurasia following the last glacial maximum. One theory that was introduced during European colonization. R1 is very common throughout all of Eurasia except East Asia and Southeast Asia. R1 (M173) is found predominantly in North American groups like the Ojibwe (50-79%), Seminole (50%), Sioux (50%), Cherokee (47%), Dogrib (40%) and Tohono O'odham (Papago) (38%).

A study of Raghavan et al. 2013 found that autosomal evidence indicates that skeletal remain of a south-central Siberian child carrying R* y-dna (Mal'ta boy-1) "is basal to modern-day western Eurasians and genetically closely related to modern-day Amerindians, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought." Sequencing of another south-central Siberian (Afontova Gora-2) revealed that "western Eurasian genetic signatures in modern-day Amerindians derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans." It is further theorized if "Mal'ta might be a missing link, a representative of the Asian population that admixed both into Europeans and Native Americans."

On FTDNA public tree, out of 626 US indigenous Americans K-YSC0000186 , all are Q , R1b-M269, R1a-M198, 1 R2-M479 and 2 most likely not tested further than R1b-M343 .

Haplogroup C-P39

Haplogroup C-M217 is mainly found in indigenous Siberians, Mongolians, and Kazakhs. Haplogroup C-M217 is the most widespread and frequently occurring branch of the greater (Y-DNA) haplogroup C-M130. Haplogroup C-M217 descendant C-P39 is most commonly found in today's Na-Dené speakers, with the highest frequency found among the Athabaskans at 42%, and at lower frequencies in some other Native American groups. This distinct and isolated branch C-P39 includes almost all the Haplogroup C-M217 Y-chromosomes found among all indigenous peoples of the Americas.

Some researchers feel that this may indicate that the Na-Dené migration occurred from the Russian Far East after the initial Paleo-Indian colonization, but prior to modern Inuit, Inupiat and Yupik expansions.

In addition to in Na-Dené peoples, haplogroup C-P39 (C2b1a1a) is also found among other Native Americans such as Algonquian- and Siouan-speaking populations. C-M217 is found among the Wayuu people of Colombia and Venezuela.

Maternal lineages

The common occurrence of the mtDNA Haplogroups A, B, C, and D among eastern Asian and Amerindian populations has long been recognized, along with the presence of Haplogroup X. As a whole, the greatest frequency of the four Amerindian associated haplogroups occurs in the Altai-Baikal region of southern Siberia. Some subclades of C and D closer to the Amerindian subclades occur among Mongolian, Amur, Japanese, Korean, and Ainu populations.

When studying human mitochondrial DNA (mtDNA) haplogroups, the results indicated until recentllyil^y that Indigenous Amerindian haplogroups, including haplogroup X, are part of a single founding East Asian population. It also indicates that the distribution of mtDNA haplogroups and the levels of sequence divergence among linguistically similar groups were the result of multiple preceding migrations from Bering Straits populations. All indigenous Amerindian mtDNA can be traced back to five haplogroups, A, B, C, D and X. More specifically, indigenous Amerindian mtDNA belongs to sub-haplogroups A2, B2, C1b, C1c, C1d, D1, and X2a (with minor groups C4c, D2a, and D4h3a).This suggests that 95% of Indigenous Amerindian mtDNA is descended from a minimal genetic founding female population, comprising sub-haplogroups A2, B2, C1b, C1c, C1d, and D1. The remaining 5% is composed of the X2a, D2a, C4c, and D4h3a sub-haplogroups.

X is one of the five mtDNA haplogroups found in Indigenous Amerindian peoples. Unlike the four main American mtDNA haplogroups (A, B, C and D), X is not at all strongly associated with east Asia. 

Haplogroup X genetic sequences diverged about 20,000 to 30,000 years ago to give two sub-groups, X1 and X2. X2's subclade X2a occurs only at a frequency of about 3% for the total current indigenous population of the Americas. However, X2a is a major mtDNA subclade in North America; among the Algonquian peoples, it comprises up to 25% of mtDNA types. It is also present in lower percentages to the west and south of this area — among the Sioux (15%), the Nuu-chah-nulth (11%–13%), the Navajo (7%), and the Yakama (5%). Haplogroup X is more strongly present in the Near East, the Caucasus, and Mediterranean Europe. The predominant theory for sub-haplogroup X2a's appearance in North America is migration along with A, B, C, and D mtDNA groups, from a source in the Altai Mountains of central Asia.

Sequencing of the mitochondrial genome from Paleo-Eskimo remains (3,500 years old) are distinct from modern Amerindians, falling within sub-haplogroup D2a1, a group observed among today's Aleutian Islanders, the Aleut and Siberian Yupik populations. This suggests that the colonizers of the far north, and subsequently Greenland, originated from later coastal populations. Then a genetic exchange in the northern extremes introduced by the Thule people (proto-Inuit) approximately 800–1,000 years ago began. These final Pre-Columbian migrants introduced haplogroups A2a and A2b to the existing Paleo-Eskimo populations of Canada and Greenland, culminating in the modern Inuit.

Frequency distribution of the main mtDNA American haplogroups in Native American populations.

A 2013 study in Nature reported that DNA found in the 24,000-year-old remains of a young boy from the archaeological Mal'ta-Buret' culture suggest that up to one-third of indigenous Americans' ancestry can be traced back to western Eurasians, who may have "had a more north-easterly distribution 24,000 years ago than commonly thought" "We estimate that 14 to 38 percent of Amerindian ancestry may originate through gene flow from this ancient population," the authors wrote. Professor Kelly Graf said,

"Our findings are significant at two levels. First, it shows that Upper Paleolithic Siberians came from a cosmopolitan population of early modern humans that spread out of Africa to Europe and Central and South Asia. Second, Paleoindian skeletons like Buhl Woman with phenotypic traits atypical of modern-day indigenous Americans can be explained as having a direct historical connection to Upper Paleolithic Siberia."

A route through Beringia is seen as more likely than the Solutrean hypothesis. An abstract in a 2012 issue of the "American Journal of Physical Anthropology" states that "The similarities in ages and geographical distributions for C4c and the previously analyzed X2a lineage provide support to the scenario of a dual origin for Paleo-Indians. Taking into account that C4c is deeply rooted in the Asian portion of the mtDNA phylogeny and is indubitably of Asian origin, the finding that C4c and X2a are characterized by parallel genetic histories definitively dismisses the controversial hypothesis of an Atlantic glacial entry route into North America."

Another study, also focused on the mtDNA (that which is inherited through only the maternal line), revealed that the indigenous people of the Americas have their maternal ancestry traced back to a few founding lineages from East Asia, which would have arrived via the Bering strait. According to this study, it is probable that the ancestors of the Native Americans would have remained for a time in the region of the Bering Strait, after which there would have been a rapid movement of settling of the Americas, taking the founding lineages to South America.

According to a 2016 study, focused on mtDNA lineages, "a small population entered the Americas via a coastal route around 16.0 ka, following previous isolation in eastern Beringia for ~2.4 to 9 thousand years after separation from eastern Siberian populations. Following a rapid movement throughout the Americas, limited gene flow in South America resulted in a marked phylogeographic structure of populations, which persisted through time. All of the ancient mitochondrial lineages detected in this study were absent from modern data sets, suggesting a high extinction rate. To investigate this further, we applied a novel principal components multiple logistic regression test to Bayesian serial coalescent simulations. The analysis supported a scenario in which European colonization caused a substantial loss of pre-Columbian lineages".

Paleoamericans

There is genetic evidence for an early wave of migration to the Americas. It is uncertain whether this "Paleoamerican" (also "Paleoamerind", not to be confused with the term Paleo-Indian used of the early phase of Amerinds proper) migration took place in the early Holocene, thus only shortly predating the main Amerind peopling of the Americas, or whether it may have reached the Americas substantially earlier, before the Last Glacial Maximum. Genetic evidence for "Paleoamerinds" consists of the presence of apparent admixture of archaic Sundadont lineages to the remote populations in the South American rain forest, and in the genetics and cranial morphology of Patagonians-Fuegians. Nomatto et al. (2009) proposed migration into Beringia occurred between 40k and 30k cal years BP, with a pre-LGM migration into the Americas followed by isolation of the northern population following closure of the ice-free corridor.

A 2016 genetic study of native peoples of the Amazonian region of Brazil (by Skoglund and Reich) showed evidence of admixture from a separate lineage of an otherwise unknown ancient people. This ancient group appears to be related to modern day "Australasian" peoples (i.e. Aboriginal Australians and Melanesians). This "Ghost population" was found in speakers of Tupian languages. They provisionally named this ancient group; "Population Y", after Ypykuéra, "which means ‘ancestor’ in the Tupi language family".

Archaeological evidence for pre-LGM human presence in the Americas was first presented in the 1970s. notably the "Luzia Woman" skull found in Brazil and the Monte Verde site in Chile, both discovered in 1975. Other notable sites of early human inhabitation found in North America include Paisley Caves, Oregon and Bluefish Caves, Canada.

Genetic analyses of HLA I and HLA II genes as well as HLA-A, -B, and -DRB1 gene frequencies links the Ainu people in northern Japan and southeastern Russia to some Indigenous peoples of the Americas, especially to populations on the Pacific Northwest Coast such as Tlingit. The scientists suggest that the main ancestor of the Ainu and of some Native American groups can be traced back to Paleolithic groups in Southern Siberia. The same lineages are also found among some Central Asians.

Old World genetic admixture

 

The current distribution of indigenous peoples (based on self-identification, not genetic data).

Substantial racial admixture has taken place during and since the European colonization of the Americas.

South and Central America

In Latin America in particular, significant racial admixture took place between the indigenous Amerind population, the European-descended colonial population, and the Sub-Saharan African populations imported as slaves. From about 1700, a Latin American terminology developed to refer to the various combinations of mixed racial descent produced by this.

Many individuals who self-identify as one race exhibit genetic evidence of a multiracial ancestry. The European conquest of South and Central America, beginning in the late 15th century, was initially executed by male soldiers and sailors from the Iberian Peninsula (Spain and Portugal).

The new soldier-settlers fathered children with Amerindian women and later with African slaves. These mixed-race children were generally identified by the Spanish colonist and Portuguese colonist as "Castas".

North America

The North American fur trade during the 16th century brought many more European men, from France, Ireland, and Great Britain, who took North Amerindian women as wives. Their children became known as "Métis" or "Bois-Brûlés" by the French colonists and "mixed-bloods", "half-breeds" or "country-born" by the English colonists and Scottish colonists.

Native Americans in the United States are more likely than any other racial group to practice racial exogamy, resulting in an ever-declining proportion of indigenous ancestry among those who claim a Native American identity. In the United States 2010 census, nearly 3 million people indicated that their race was Native American (including Alaska Native). This is based on self-identification, and there are no formal defining criteria for this designation. Especially numerous was the self-identification of Cherokee ethnic origin, a phenomenon dubbed the "Cherokee Syndrome." The context is the cultivation of an opportunistic ethnic identity related to the perceived prestige associated with Native American ancestry. Native American identity in the Eastern United States is mostly detached from genetic descent, and especially embraced by people of predominantly European ancestry. Some tribes have adopted criteria of racial preservation, usually through a Certificate of Degree of Indian Blood, and practice disenrollment of tribal members unable to provide proof of Native American ancestry. This topic has become a contentious issue in Native American reservation politics.

Ancient Beringians

25 kya Beringia during the LGM 16-14 kya peopling of the Americas just after the LGM

Recent archaeological findings in Alaska have shed light on the existence of a previously unknown Native American population that has been academically named "Ancient Beringians." Although it is popularly agreed among archeologists that early settlers had crossed into Alaska from Russia through the Bering Strait land bridge, the issue of whether or not there was one founding group or several waves of migration is a controversial and prevalent debate among academics in the field today. In 2018, the sequenced DNA of a native girl, whose remains were found at the Sun River archaeological site in Alaska in 2013, proved not to match the two recognized branches of Native Americans and instead belonged to the early population of Ancient Beringians. This breakthrough is said to be the first direct genomic evidence that there was potentially only one wave of migration in the Americas that occurred, with genetic branching and division transpiring after the fact. The migration wave is estimated to have emerged about 20,000 years ago. The Ancient Beringians are said to be a common ancestral group among contemporary Native American populations today, which differs in results collected from previous research that suggests that modern populations are descendants of either Northern and Southern branches. Experts were also able to use wider genetic evidence to establish that the split between the Northern and Southern American branches of civilization from the Ancient Beringians in Alaska only occurred about 17,000 and 14,000 years, further challenging the concept of multiple migration waves occurring during the very first stages of settlement.

Blood groups

Frequency of O group in indigenous populations. Note the predominance of this group in Indigenous Americans.

Prior to the 1952 confirmation of DNA as the hereditary material by Alfred Hershey and Martha Chase, scientists used blood proteins to study human genetic variation. The ABO blood group system is widely credited to have been discovered by the Austrian Karl Landsteiner, who found three different blood types in 1900. Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO gene) with three alleles: i, I^A, and I^B.

Research by Ludwik and Hanka Herschfeld during World War I found that the frequencies of blood groups A, B and O differed greatly from region to region. The "O" blood type (usually resulting from the absence of both A and B alleles) is very common around the world, with a rate of 63% in all human populations. Type "O" is the primary blood type among the indigenous populations of the Americas, in-particular within Central and South America populations, with a frequency of nearly 100%. In indigenous North American populations the frequency of type "A" ranges from 16% to 82%. This suggests again that the initial Amerindians evolved from an isolated population with a minimal number of individuals.

The standard explanation for such a high population of Native Americans with blood type O comes from the idea of Genetic drift, in which the small nature of Native American populations meant the almost complete absence of any other blood gene being passed down through generations. Other related explanations include the Bottleneck explanation which states that there were high frequencies of blood type A and B among Native Americans but severe population decline during the 1500s and 1600s caused by the introduction of disease from Europe resulted in the massive death toll of those with blood types A and B. Coincidentally, a large amount of the survivors were type O.

Distribution of ABO blood types
in various modern Indigenous Amerindian populations
Test results as of 2008

PEOPLE GROUP	O (%)	A (%)	B (%)	AB (%)
Blackfoot Confederacy (N. American Indian)	17	82	0	1
Bororo (Brazil)	100	0	0	0
Eskimos (Alaska)	38	44	13	5
Inuit (Eastern Canada & Greenland)	54	36	23	8
Hawaiians (Polynesians, non-Amerindian)	37	61	2	1
Indigenous North Americans (as a whole Native Nations/First Nations)	79	16	4	1
Maya (modern)	98	1	1	1
Navajo	73	27	0	0
Peru	100	0	0	0

European diseases and genetic modification

A team led by Ripan Malhi, an anthropologist at the University of Illinois in Urbana, conducted a study where they used a scientific technique known as whole exome sequencing to test immune-related gene variants within Native Americans. Through analyzing ancient and modern native DNA, it was found that HLA-DQA1, a variant gene that codes for protein in charge of differentiating between healthy cells from invading viruses and bacteria were present in nearly 100% of ancient remains but only 36% in modern Native Americans. These finding suggest that European-borne epidemics such as smallpox altered the disease landscape of the Americas, leaving survivors of these outbreaks less likely to carry variants like HLA-DQA1. This made them less able to cope with new diseases. The change in genetic makeup is measured by scientists to have occurred around 175 years ago, during a time when the smallpox epidemic was ranging through the Americas.

Epoch (astronomy)

From Wikipedia, the free encyclopedia

 

In astronomy, an epoch is a moment in time used as a reference point for some time-varying astronomical quantity, such as the celestial coordinates or elliptical orbital elements of a celestial body, because these are subject to perturbations and vary with time. These time-varying astronomical quantities might include, for example, the mean longitude or mean anomaly of a body, the node of its orbit relative to a reference plane, the direction of the apogee or aphelion of its orbit, or the size of the major axis of its orbit.

The main use of astronomical quantities specified in this way is to calculate other relevant parameters of motion, in order to predict future positions and velocities. The applied tools of the disciplines of celestial mechanics or its subfield orbital mechanics (for predicting orbital paths and positions for bodies in motion under the gravitational effects of other bodies) can be used to generate an ephemeris, a table of values giving the positions and velocities of astronomical objects in the sky at a given time or times.

Astronomical quantities can be specified in any of several ways, for example, as a polynomial function of the time-interval, with an epoch as a temporal point of origin (this is a common current way of using an epoch). Alternatively, the time-varying astronomical quantity can be expressed as a constant, equal to the measure that it had at the epoch, leaving its variation over time to be specified in some other way—for example, by a table, as was common during the 17th and 18th centuries.

The word epoch was often used in a different way in older astronomical literature, e.g. during the 18th century, in connection with astronomical tables. At that time, it was customary to denote as "epochs", not the standard date and time of origin for time-varying astronomical quantities, but rather the values at that date and time of those time-varying quantities themselves. In accordance with that alternative historical usage, an expression such as 'correcting the epochs' would refer to the adjustment, usually by a small amount, of the values of the tabulated astronomical quantities applicable to a fixed standard date and time of reference (and not, as might be expected from current usage, to a change from one date and time of reference to a different date and time).

Epoch versus equinox

Astronomical data are often specified not only in their relation to an epoch or date of reference but also in their relations to other conditions of reference, such as coordinate systems specified by "equinox", or "equinox and equator", or "equinox and ecliptic" – when these are needed for fully specifying astronomical data of the considered type.

Date-references for coordinate systems

When the data are dependent for their values on a particular coordinate system, the date of that coordinate system needs to be specified directly or indirectly.

Celestial coordinate systems most commonly used in astronomy are equatorial coordinates and ecliptic coordinates. These are defined relative to the (moving) vernal equinox position, which itself is determined by the orientations of the Earth's rotation axis and orbit around the Sun. Their orientations vary (though slowly, e.g. due to precession), and there is an infinity of such coordinate systems possible. Thus the coordinate systems most used in astronomy need their own date-reference because the coordinate systems of that type are themselves in motion, e.g. by the precession of the equinoxes, nowadays often resolved into precessional components, separate precessions of the equator and of the ecliptic.

The epoch of the coordinate system need not be the same, and often in practice is not the same, as the epoch for the data themselves.

The difference between reference to an epoch alone, and a reference to a certain equinox with equator or ecliptic, is therefore that the reference to the epoch contributes to specifying the date of the values of astronomical variables themselves; while the reference to an equinox along with equator/ecliptic, of a certain date, addresses the identification of, or changes in, the coordinate system in terms of which those astronomical variables are expressed. (Sometimes the word 'equinox' may be used alone, e.g. where it is obvious from the context to users of the data in which form the considered astronomical variables are expressed, in equatorial form or ecliptic form.)

The equinox with equator/ecliptic of a given date defines which coordinate system is used. Most standard coordinates in use today refer to 2000 TT (i.e. to 12h on the Terrestrial Time scale on January 1, 2000), which occurred about 64 seconds sooner than noon UT1 on the same date (see ΔT). Before about 1984, coordinate systems dated to 1950 or 1900 were commonly used.

There is a special meaning of the expression "equinox (and ecliptic/equator) of date". When coordinates are expressed as polynomials in time relative to a reference frame defined in this way, that means the values obtained for the coordinates in respect of any interval t after the stated epoch, are in terms of the coordinate system of the same date as the obtained values themselves, i.e. the date of the coordinate system is equal to (epoch + t).

It can be seen that the date of the coordinate system need not be the same as the epoch of the astronomical quantities themselves. But in that case (apart from the "equinox of date" case described above), two dates will be associated with the data: one date is the epoch for the time-dependent expressions giving the values, and the other date is that of the coordinate system in which the values are expressed.

For example, orbital elements, especially osculating elements for minor planets, are routinely given with reference to two dates: first, relative to a recent epoch for all of the elements: but some of the data are dependent on a chosen coordinate system, and then it is usual to specify the coordinate system of a standard epoch which often is not the same as the epoch of the data. An example is as follows: For minor planet (5145) Pholus, orbital elements have been given including the following data:

Epoch 2010 Jan. 4.0 TT . . . = JDT 2455200.5
M 72.00071 . . . . . . . .(2000.0)
n. 0.01076162 .. . . . Peri . 354.75938
a 20.3181594 . . . . . Node . 119.42656
e. 0.5715321 . . . . . Incl .. 24.66109

where the epoch is expressed in terms of Terrestrial Time, with an equivalent Julian date. Four of the elements are independent of any particular coordinate system: M is mean anomaly (deg), n: mean daily motion (deg/d), a: size of semi-major axis (AU), e: eccentricity (dimensionless). But the argument of perihelion, longitude of the ascending node and the inclination are all coordinate-dependent, and are specified relative to the reference frame of the equinox and ecliptic of another date "2000.0", otherwise known as J2000, i.e. January 1.5, 2000 (12h on January 1) or JD 2451545.0.

Epochs and periods of validity

In the particular set of coordinates exampled above, much of the elements has been omitted as unknown or undetermined; for example, the element n allows an approximate time-dependence of the element M to be calculated, but the other elements and n itself are treated as constant, which represents a temporary approximation (see Osculating elements).

Thus a particular coordinate system (equinox and equator/ecliptic of a particular date, such as J2000.0) could be used forever, but a set of osculating elements for a particular epoch may only be (approximately) valid for a rather limited time, because osculating elements such as those exampled above do not show the effect of future perturbations which will change the values of the elements.

Nevertheless, the period of validity is a different matter in principle and not the result of the use of an epoch to express the data. In other cases, e.g. the case of a complete analytical theory of the motion of some astronomical body, all of the elements will usually be given in the form of polynomials in interval of time from the epoch, and they will also be accompanied by trigonometrical terms of periodical perturbations specified appropriately. In that case, their period of validity may stretch over several centuries or even millennia on either side of the stated epoch.

Some data and some epochs have a long period of use for other reasons. For example, the boundaries of the IAU constellations are specified relative to an equinox from near the beginning of the year 1875. This is a matter of convention, but the convention is defined in terms of the equator and ecliptic as they were in 1875. To find out in which constellation a particular comet stands today, the current position of that comet must be expressed in the coordinate system of 1875 (equinox/equator of 1875). Thus that coordinate system can still be used today, even though most comet predictions made originally for 1875 (epoch = 1875) would no longer, because of the lack of information about their time-dependence and perturbations, be useful today.

Changing the standard equinox and epoch

To calculate the visibility of a celestial object for an observer at a specific time and place on the Earth, the coordinates of the object are needed relative to a coordinate system of current date. If coordinates relative to some other date are used, then that will cause errors in the results. The magnitude of those errors increases with the time difference between the date and time of observation and the date of the coordinate system used, because of the precession of the equinoxes. If the time difference is small, then fairly easy and small corrections for the precession may well suffice. If the time difference gets large, then fuller and more accurate corrections must be applied. For this reason, a star position read from a star atlas or catalog based on a sufficiently old equinox and equator cannot be used without corrections if reasonable accuracy is required.

Additionally, stars move relative to each other through space. Apparent motion across the sky relative to other stars is called proper motion. Most stars have very small proper motions, but a few have proper motions that accumulate to noticeable distances after a few tens of years. So, some stellar positions read from a star atlas or catalog for a sufficiently old epoch require proper motion corrections as well, for reasonable accuracy.

Due to precession and proper motion, star data become less useful as the age of the observations and their epoch, and the equinox and equator to which they are referred, get older. After a while, it is easier or better to switch to newer data, generally referred to a newer epoch and equinox/equator, than to keep applying corrections to the older data.

Specifying an epoch or equinox

Epochs and equinoxes are moments in time, so they can be specified in the same way as moments that indicate things other than epochs and equinoxes. The following standard ways of specifying epochs and equinoxes seem most popular:

• Julian days, e.g., JD 2433282.4235 for January 0.9235, 1950 TT
• Besselian years (see below), e.g., 1950.0 or B1950.0 for January 0.9235, 1950 TT
• Julian years, e.g., J2000.0 for January 1.5, 2000, TT

All three of these are expressed in TT = Terrestrial Time.

Besselian years, used mostly for star positions, can be encountered in older catalogs but are now becoming obsolete. The Hipparcos catalog summary, for example, defines the "catalog epoch" as J1991.25 (8.75 Julian years before January 1.5, 2000, TT, e.g., April 2.5625, 1991 TT).

Besselian years

A Besselian year is named after the German mathematician and astronomer Friedrich Bessel (1784–1846). Meeus defines the beginning of a Besselian year to be the moment at which the mean longitude of the Sun, including the effect of aberration and measured from the mean equinox of the date, is exactly 280 degrees. This moment falls near the beginning of the corresponding Gregorian year. The definition depended on a particular theory of the orbit of the Earth around the Sun, that of Newcomb (1895), which is now obsolete; for that reason among others, the use of Besselian years has also become or is becoming obsolete.

Lieske says that a "Besselian epoch" can be calculated from the Julian date according to

B = 1900.0 + (Julian date − 2415020.31352) / 365.242198781

Lieske's definition is not exactly consistent with the earlier definition in terms of the mean longitude of the Sun. When using Besselian years, specify which definition is being used.

To distinguish between calendar years and Besselian years, it became customary to add ".0" to the Besselian years. Since the switch to Julian years in the mid-1980s, it has become customary to prefix "B" to Besselian years. So, "1950" is the calendar year 1950, and "1950.0" = "B1950.0" is the beginning of Besselian year 1950.

• The IAU constellation boundaries are defined in the equatorial coordinate system relative to the equinox of B1875.0.
• The Henry Draper Catalog uses the equinox B1900.0.
• The classical star atlas Tabulae Caelestes used B1925.0 as its equinox.

According to Meeus, and also according to the formula given above,

• B1900.0 = JDE 2415020.3135 = 1900 January 0.8135 TT
• B1950.0 = JDE 2433282.4235 = 1950 January 0.9235 TT

Julian Dates and J2000

A Julian year is an interval with the length of a mean year in the Julian calendar, i.e. 365.25 days. This interval measure does not itself define any epoch: the Gregorian calendar is in general use for dating. But, standard conventional epochs which are not Besselian epochs have been often designated nowadays with a prefix "J", and the calendar date to which they refer is widely known, although not always the same date in the year: thus "J2000" refers to the instant of 12 noon (midday) on January 1, 2000, and J1900 refers to the instant of 12 noon on January 0, 1900, equal to December 31, 1899. It is also usual now to specify on what time scale the time of day is expressed in that epoch-designation, e.g. often Terrestrial Time.

In addition, an epoch optionally prefixed by "J" and designated as a year with decimals (2000 + x), where x is either positive or negative and is quoted to 1 or 2 decimal places, has come to mean a date that is an interval of x Julian years of 365.25 days away from the epoch J2000 = JD 2451545.0 (TT), still corresponding (in spite of the use of the prefix "J" or word "Julian") to the Gregorian calendar date of January 1, 2000, at 12h TT (about 64 seconds before noon UTC on the same calendar day). See also Julian year (astronomy). Like the Besselian epoch, an arbitrary Julian epoch is therefore related to the Julian date by

J = 2000 + (Julian date − 2451545.0) ÷ 365.25

The IAU decided at their General Assembly of 1976 that the new standard equinox of J2000.0 should be used starting in 1984. Before that, the equinox of B1950.0 seems to have been the standard.

Different astronomers or groups of astronomers used to define individually, but today standard epochs are generally defined by international agreement through the IAU, so astronomers worldwide can collaborate more effectively. It is inefficient and error-prone if data or observations of one group have to be translated in non-standard ways so that other groups could compare the data with information from other sources. An example of how this works: if a star's position is measured by someone today, they then use a standard transformation to obtain the position expressed in terms of the standard reference frame of J2000, and it is often then this J2000 position which is shared with others.

On the other hand, there has also been an astronomical tradition of retaining observations in just the form in which they were made, so that others can later correct the reductions to standard if that proves desirable, as has sometimes occurred.

The currently-used standard epoch "J2000" is defined by international agreement to be equivalent to:

1. The Gregorian date January 1, 2000, at 12:00 TT (Terrestrial Time).
2. The Julian date 2451545.0 TT (Terrestrial Time).
3. January 1, 2000, 11:59:27.816 TAI (International Atomic Time).
4. January 1, 2000, 11:58:55.816 UTC (Coordinated Universal Time).

Epoch of the day

Over shorter timescales, there are a variety of practices for defining when each day begins. In ordinary usage, the civil day is reckoned by the midnight epoch, that is, the civil day begins at midnight. But in older astronomical usage, it was usual, until January 1, 1925, to reckon by a noon epoch, 12 hours after the start of the civil day of the same denomination, so that the day began when the mean sun crossed the meridian at noon. This is still reflected in the definition of J2000, which started at noon, Terrestrial Time.

In traditional cultures and in antiquity other epochs were used. In ancient Egypt, days were reckoned from sunrise to sunrise, following a morning epoch. This may be related to the fact that the Egyptians regulated their year by the heliacal rising of the star Sirius, a phenomenon which occurs in the morning just before dawn.

In some cultures following a lunar or lunisolar calendar, in which the beginning of the month is determined by the appearance of the New Moon in the evening, the beginning of the day was reckoned from sunset to sunset, following an evening epoch, e.g. the Jewish and Islamic calendars and in Medieval Western Europe in reckoning the dates of religious festivals, while in others a morning epoch was followed, e.g. the Hindu and Buddhist calendars.

Benzatropine

From Wikipedia, the free encyclopedia

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

 

Benzatropine

Clinical data
Trade names	Cogentin, others
Other names	benzatropine (BAN UK), benztropine (USAN US)
AHFS/Drugs.com	Monograph
License data	US DailyMed: Benztropine
Pregnancy category	AU: B2 US: N (Not classified yet)
Routes of administration	By mouth, IM, IV
ATC code	N04AC01 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Metabolism	Hepatic
Elimination half-life	12-24 hours
Excretion	Urine
Identifiers
IUPAC name[show]
CAS Number	86-13-5
PubChem CID	1201549
IUPHAR/BPS	7601
DrugBank	DB00245
ChemSpider	16736541
UNII	1NHL2J4X8K
ChEBI	CHEBI:3048
ChEMBL	ChEMBL1201203
CompTox Dashboard (EPA)	DTXSID9022659
Chemical and physical data
Formula	C21H25NO
Molar mass	307.437 g·mol−1
3D model (JSmol)	Interactive image
SMILES[show]
InChI[show]
(what is this?)  (verify)

Benzatropine (INN^[1]), known as benztropine in the United States and Japan, is a medication used to treat a type of movement disorder due to antipsychotics known as dystonia and parkinsonism. It is not useful for tardive dyskinesia. It is taken by mouth or by injection into a vein or muscle. Benefits are seen within two hours and last for up to ten hours.

Common side effects include dry mouth, blurry vision, nausea, and constipation. Serious side effect may include urinary retention, hallucinations, hyperthermia, and poor coordination. It is unclear if use during pregnancy or breastfeeding is safe. Benzatropine is an anticholinergic which works by blocking the activity of the muscarinic acetylcholine receptor.

Benzatropine was approved for medical use in the United States in 1954. It is available as a generic medication. In 2017, it was the 226th most commonly prescribed medication in the United States, with more than two million prescriptions. It is sold under the brand name Cogentin among others.

Medical uses

Benzatropine is used to reduce extrapyramidal side effects of antipsychotic treatment. Benzatropine is also a second-line drug for the treatment of Parkinson's disease. It improves tremor, and may alleviate rigidity and bradykinesia. Benzatropine is also sometimes used for the treatment of dystonia, a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.

Adverse effects

These are principally anticholinergic:

• Dry mouth
• Blurred vision
• Cognitive changes
• Drowsiness
• Constipation
• Urinary retention
• Tachycardia
• Anorexia
• Severe delirium and hallucinations (in overdose)

While some studies suggest that use of anticholinergics increases the risk of tardive dyskinesia (a long-term side effect of antipsychotics), other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia, although symptoms may be worsened.

Drugs that decrease cholinergic transmission may impair storage of new information into long-term memory. Anticholinergic agents can also impair time perception.

Pharmacology

Benzatropine is a centrally acting anticholinergic/antihistamine agent. It is a selective M1 muscarinic acetylcholine receptor antagonist. Benzatropine partially blocks cholinergic activity in the basal ganglia and has also been shown to increase the availability of dopamine by blocking its reuptake and storage in central sites, and as a result, increasing dopaminergic activity. Animal studies have indicated that anticholinergic activity of benzatropine is approximately one-half that of atropine, while its antihistamine activity approaches that of mepyramine. Its anticholinergic effects have been established as therapeutically significant in the management of Parkinsonism. Benzatropine antagonizes the effect of acetylcholine, decreasing the imbalance between the neurotransmitters acetylcholine and dopamine, which may improve the symptoms of early Parkinson's disease.

Benzatropine analogues are atypical dopamine reuptake inhibitors, which might make them useful for people with akathisia secondary to antipsychotic therapy.

Benzatropine also acts as a functional inhibitor of acid sphingomyelinase (FIASMA).

Benzatropine has been also identified, by a high throughput screening approach, as a potent differentiating agent for oligodendrocytes, possibly working through M1 and M3 muscarinic receptors. In preclinical models for multiple sclerosis, benzatropine decreased clinical symptoms and enhanced re-myelination.

Other animals

In veterinary medicine, benzatropine is used to treat priapism in stallions.

Naming

Since 1959, benzatropine is the official international nonproprietary name of the medication under the INN scheme, the medication naming system coordinated by the World Health Organization; it is also the British Approved Name (BAN) given in the British Pharmacopoeia, and has been the official nonproprietary name in Australia since 2015. Regional variations of the "a" spelling are also used in French, Italian, Portuguese, and Spanish, as well as Latin (all medications are assigned a Latin name by WHO).

"Benztropine" is the official United States Adopted Name (USAN), the medication naming system coordinated by the USAN Council, co-sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA). It is also the Japanese Accepted Name (JAN) and was used in Australia until 2015, when it was harmonized with the INN.

Both names may be modified to account for the methanesulfonate salt as which the medication is formulated: the modified INN (INNm) and BAN (BANM) is benzatropine mesilate, while the modified USAN is benztropine mesylate. The modified JAN is a hybrid form, benztropine mesilate.

The misspelling benzotropine is also occasionally seen in the literature.