Introduction to genetics

From Wikipedia, the free encyclopedia

Genetics is the study of heredity and variations. Heredity and variations are controlled by genes—what they are, what they do, and how they work. Genes inside the nucleus of a cell are strung together in such a way that the sequence carries information: that information determines how living organisms inherit various features (phenotypic traits). For example, offspring produced by sexual reproduction usually look similar to each of their parents because they have inherited some of each of their parents' genes. Genetics identifies which features are inherited, and explains how these features pass from generation to generation. In addition to inheritance, genetics studies how genes are turned on and off to control what substances are made in a cell—gene expression; and how a cell divides—mitosis or meiosis.

Some phenotypic traits can be seen, such as eye color while others can only be detected, such as blood type or intelligence. Traits determined by genes can be modified by the animal's surroundings (environment): for example, the general design of a tiger's stripes is inherited, but the specific stripe pattern is determined by the tiger's surroundings. Another example is a person's height: it is determined by both genetics and nutrition.

Chromosomes are tiny packages which contain one DNA molecule and its associated proteins. Humans have 46 chromosomes (23 pairs). This number varies between species—for example, many primates have 24 pairs. Meiosis creates special cells, sperm in males and eggs in females, which only have 23 chromosomes. These two cells merge into one during the fertilization stage of sexual reproduction, creating a zygote. In a zygote, a nucleic acid double helix divides, with each single helix occupying one of the daughter cells, resulting in half the normal number of genes. By the time the zygote divides again, genetic recombination has created a new embryo with 23 pairs of chromosomes, half from each parent. Mating and resultant mate choice result in sexual selection. In normal cell division (mitosis) is possible when the double helix separates, and a complement of each separated half is made, resulting in two identical double helices in one cell, with each occupying one of the two new daughter cells created when the cell divides.

Chromosomes all contain DNA made up of four nucleotides, abbreviated C (cytosine), G (guanine), A (adenine), or T (thymine), which line up in a particular sequence and make a long string. There are two strings of nucleotides coiled around one another in each chromosome: a double helix. C on one string is always opposite from G on the other string; A is always opposite T. There are about 3.2 billion nucleotide pairs on all the human chromosomes: this is the human genome. The order of the nucleotides carries genetic information, whose rules are defined by the genetic code, similar to how the order of letters on a page of text carries information. Three nucleotides in a row—a triplet—carry one unit of information: a codon.

The genetic code not only controls inheritance: it also controls gene expression, which occurs when a portion of the double helix is uncoiled, exposing a series of the nucleotides, which are within the interior of the DNA. This series of exposed triplets (codons) carries the information to allow machinery in the cell to "read" the codons on the exposed DNA, which results in the making of RNA molecules. RNA in turn makes either amino acids or microRNA, which are responsible for all of the structure and function of a living organism; i.e. they determine all the features of the cell and thus the entire individual. Closing the uncoiled segment turns off the gene.

Heritability means the information in a given gene is not always exactly the same in every individual in that species, so the same gene in different individuals does not give exactly the same instructions. Each unique form of a single gene is called an allele; different forms are collectively called polymorphisms. As an example, one allele for the gene for hair color and skin cell pigmentation could instruct the body to produce black pigment, producing black hair and pigmented skin; while a different allele of the same gene in a different individual could give garbled instructions that would result in a failure to produce any pigment, giving white hair and no pigmented skin: albinism.  Mutations are random changes in genes creating new alleles, which in turn produce new traits, which could help, harm, or have no new effect on the individual's likelihood of survival; thus, mutations are the basis for evolution.

Inheritance in biology

Genes and inheritance

A section of DNA; the sequence of the plate-like units (nucleotides) in the center carries information.

Red hair is a recessive trait.

Genes are pieces of DNA that contain information for synthesis of ribonucleic acids (RNAs) or polypeptides. Genes are inherited as units, with two parents dividing out copies of their genes to their offspring. This process can be compared with mixing two hands of cards, shuffling them, and then dealing them out again. Humans have two copies of each of their genes, and make copies that are found in eggs or sperm—but they only include one copy of each type of gene. An egg and sperm join to form a complete set of genes. The eventually resulting offspring has the same number of genes as their parents, but for any gene one of their two copies comes from their father, and one from their mother.^[1]

The effects of this mixing depend on the types (the alleles) of the gene. If the father has two copies of an allele for red hair, and the mother has two copies for brown hair, all their children get the two alleles that give different instructions, one for red hair and one for brown. The hair color of these children depends on how these alleles work together. If one allele dominates the instructions from another, it is called the dominant allele, and the allele that is overridden is called the recessive allele. In the case of a daughter with alleles for both red and brown hair, brown is dominant and she ends up with brown hair.^[2]

Although the red color allele is still there in this brown-haired girl, it doesn't show. This is a difference between what you see on the surface (the traits of an organism, called its phenotype) and the genes within the organism (its genotype). In this example you can call the allele for brown "B" and the allele for red "b". (It is normal to write dominant alleles with capital letters and recessive ones with lower-case letters.) The brown hair daughter has the "brown hair phenotype" but her genotype is Bb, with one copy of the B allele, and one of the b allele.

Now imagine that this woman grows up and has children with a brown-haired man who also has a Bb genotype. Her eggs will be a mixture of two types, one sort containing the B allele, and one sort the b allele. Similarly, her partner will produce a mix of two types of sperm containing one or the other of these two alleles. When the transmitted genes are joined up in their offspring, these children have a chance of getting either brown or red hair, since they could get a genotype of BB = brown hair, Bb = brown hair or bb = red hair. In this generation, there is therefore a chance of the recessive allele showing itself in the phenotype of the children—some of them may have red hair like their grandfather.^[2]

Many traits are inherited in a more complicated way than the example above. This can happen when there are several genes involved, each contributing a small part to the end result. Tall people tend to have tall children because their children get a package of many alleles that each contribute a bit to how much they grow. However, there are not clear groups of "short people" and "tall people", like there are groups of people with brown or red hair. This is because of the large number of genes involved; this makes the trait very variable and people are of many different heights.^[3] Despite a common misconception, the green/blue eye traits are also inherited in this complex inheritance model.^[4] Inheritance can also be complicated when the trait depends on interaction between genetics and environment. For example, malnutrition does not change traits like eye color, but can stunt growth.^[5]

Inherited diseases

Some diseases are hereditary and run in families; others, such as infectious diseases, are caused by the environment. Other diseases come from a combination of genes and the environment.^[6] Genetic disorders are diseases that are caused by a single allele of a gene and are inherited in families. These include Huntington's disease, Cystic fibrosis or Duchenne muscular dystrophy. Cystic fibrosis, for example, is caused by mutations in a single gene called CFTR and is inherited as a recessive trait.^[7]

Other diseases are influenced by genetics, but the genes a person gets from their parents only change their risk of getting a disease. Most of these diseases are inherited in a complex way, with either multiple genes involved, or coming from both genes and the environment. As an example, the risk of breast cancer is 50 times higher in the families most at risk, compared to the families least at risk. This variation is probably due to a large number of alleles, each changing the risk a little bit.^[8] Several of the genes have been identified, such as BRCA1 and BRCA2, but not all of them. However, although some of the risk is genetic, the risk of this cancer is also increased by being overweight, drinking a lot of alcohol and not exercising.^[9] A woman's risk of breast cancer therefore comes from a large number of alleles interacting with her environment, so it is very hard to predict.

How genes work

Genes make proteins

The function of genes is to provide the information needed to make molecules called proteins in cells.^[1] Cells are the smallest independent parts of organisms: the human body contains about 100 trillion cells, while very small organisms like bacteria are just one single cell. A cell is like a miniature and very complex factory that can make all the parts needed to produce a copy of itself, which happens when cells divide. There is a simple division of labor in cells—genes give instructions and proteins carry out these instructions, tasks like building a new copy of a cell, or repairing damage.^[10] Each type of protein is a specialist that only does one job, so if a cell needs to do something new, it must make a new protein to do this job. Similarly, if a cell needs to do something faster or slower than before, it makes more or less of the protein responsible. Genes tell cells what to do by telling them which proteins to make and in what amounts.

Genes are expressed by being transcribed into RNA, and this RNA then translated into protein.

Proteins are made of a chain of 20 different types of amino acid molecules. This chain folds up into a compact shape, rather like an untidy ball of string. The shape of the protein is determined by the sequence of amino acids along its chain and it is this shape that, in turn, determines what the protein does.^[10] For example, some proteins have parts of their surface that perfectly match the shape of another molecule, allowing the protein to bind to this molecule very tightly. Other proteins are enzymes, which are like tiny machines that alter other molecules.^[11]

The information in DNA is held in the sequence of the repeating units along the DNA chain.^[12] These units are four types of nucleotides (A,T,G and C) and the sequence of nucleotides stores information in an alphabet called the genetic code. When a gene is read by a cell the DNA sequence is copied into a very similar molecule called RNA (this process is called transcription). Transcription is controlled by other DNA sequences (such as promoters), which show a cell where genes are, and control how often they are copied. The RNA copy made from a gene is then fed through a structure called a ribosome, which translates the sequence of nucleotides in the RNA into the correct sequence of amino acids and joins these amino acids together to make a complete protein chain. The new protein then folds up into its active form. The process of moving information from the language of RNA into the language of amino acids is called translation.^[13]
 

DNA replication. DNA is unwound and nucleotides are matched to make two new strands.

If the sequence of the nucleotides in a gene changes, the sequence of the amino acids in the protein it produces may also change—if part of a gene is deleted, the protein produced is shorter and may not work any more.^[10] This is the reason why different alleles of a gene can have different effects in an organism. As an example, hair color depends on how much of a dark substance called melanin is put into the hair as it grows. If a person has a normal set of the genes involved in making melanin, they make all the proteins needed and they grow dark hair. However, if the alleles for a particular protein have different sequences and produce proteins that can't do their jobs, no melanin is produced and the person has white skin and hair (albinism).^[14]

Genes are copied

Genes are copied each time a cell divides into two new cells. The process that copies DNA is called DNA replication.^[12] It is through a similar process that a child inherits genes from its parents, when a copy from the mother is mixed with a copy from the father.
DNA can be copied very easily and accurately because each piece of DNA can direct the creation of a new copy of its information. This is because DNA is made of two strands that pair together like the two sides of a zipper. The nucleotides are in the center, like the teeth in the zipper, and pair up to hold the two strands together. Importantly, the four different sorts of nucleotides are different shapes, so for the strands to close up properly, an A nucleotide must go opposite a T nucleotide, and a G opposite a C. This exact pairing is called base pairing.^[12]

When DNA is copied, the two strands of the old DNA are pulled apart by enzymes; then they pair up with new nucleotides and then close. This produces two new pieces of DNA, each containing one strand from the old DNA and one newly made strand. This process is not predictably perfect as proteins attach to a nucleotide while they are building and cause a change in the sequence of that gene. These changes in DNA sequence are called mutations.^[15] Mutations produce new alleles of genes. Sometimes these changes stop the functioning of that gene or make it serve another advantageous function, such as the melanin genes discussed above. These mutations and their effects on the traits of organisms are one of the causes of evolution.^[16]

Genes and evolution

Mice with different coat colors

A population of organisms evolves when an inherited trait becomes more common or less common over time.^[16] For instance, all the mice living on an island would be a single population of mice: some with white fur, some gray. If over generations, white mice became more frequent and gray mice less frequent, then the color of the fur in this population of mice would be evolving. In terms of genetics, this is called an increase in allele frequency.

Alleles become more or less common either by chance in a process called genetic drift, or by natural selection.^[17] In natural selection, if an allele makes it more likely for an organism to survive and reproduce, then over time this allele becomes more common. But if an allele is harmful, natural selection makes it less common. In the above example, if the island were getting colder each year and snow became present for much of the time, then the allele for white fur would favor survival, since predators would be less likely to see them against the snow, and more likely to see the gray mice. Over time white mice would become more and more frequent, while gray mice less and less.

Mutations create new alleles. These alleles have new DNA sequences and can produce proteins with new properties.^[18] So if an island was populated entirely by black mice, mutations could happen creating alleles for white fur. The combination of mutations creating new alleles at random, and natural selection picking out those that are useful, causes adaptation. This is when organisms change in ways that help them to survive and reproduce. Many such changes, studied in evolutionary developmental biology, affect the way the embryo develops into an adult body.

Genetic engineering

Since traits come from the genes in a cell, putting a new piece of DNA into a cell can produce a new trait. This is how genetic engineering works. For example, rice can be given genes from a maize and a soil bacteria so the rice produces beta-carotene, which the body converts to Vitamin A.^[19] This can help children suffering from Vitamin A deficiency. Another gene being put into some crops comes from the bacterium Bacillus thuringiensis; the gene makes a protein that is an insecticide. The insecticide kills insects that eat the plants, but is harmless to people.^[20] In these plants, the new genes are put into the plant before it is grown, so the genes are in every part of the plant, including its seeds.^[21] The plant's offspring inherit the new genes, which has led to concern about the spread of new traits into wild plants.^[22]
The kind of technology used in genetic engineering is also being developed to treat people with genetic disorders in an experimental medical technique called gene therapy.^[23] However, here the new gene is put in after the person has grown up and become ill, so any new gene is not inherited by their children. Gene therapy works by trying to replace the allele that causes the disease with an allele that works properly.

Infrared-light-based Wi-Fi network is 100 times faster

March 22, 2017
Original link:  http://www.kurzweilai.net/infrared-light-based-wi-fi-network-is-100-times-faster

Schematic of a beam of white light being dispersed by a prism into different wavelengths, similar in prinicple to how a new near-infrared WiFi system works (credit: Lucas V. Barbosa/CC)

A new infrared-light WiFi network can provide more than 40 gigabits per second (Gbps) for each user* — about 100 times faster than current WiFi systems — say researchers at Eindhoven University of Technology (TU/e) in the Netherlands.

The TU/e WiFi design was inspired by experimental systems using ceiling LED lights (such as Oregon State University’s experimental WiFiFO, or WiFi Free space Optic, system), which can increase the total per-user speed of WiFi systems and extend the range to multiple rooms, while avoiding interference from neighboring WiFi systems. (However, WiFiFo is limited to 100 Mbps.)

Experimental Oregon State University system uses LED lighting to boost the bandwidth of Wi-Fi systems and extend range (credit: Thinh Nguyen/Oregon State University)

Near-infrared light

Instead of visible light, the TU/e system uses invisible near-infrared light.** Supplied by a fiber optic cable, a few central “light antennas” (mounted on the ceiling, for instance) each use a pair of ”passive diffraction gratings” that radiate light rays of different wavelengths at different angles.

That allows for directing the light beams to specific users. The network tracks the precise location of every wireless device, using a radio signal transmitted in the return direction.***

The TU/e system uses infrared light with a wavelength of 1500 nanometers (a frequency of 200 terahertz, or 40,000 times higher than 5GHz), allowing for significantly increased capacity. The system has so far used the light rays only for downloading; uploads are still done using WiFi radio signals, since much less capacity is usually needed for uploading.

The researchers expect it will take five years or more for the new technology to be commercially available. The first devices to be connected will likely be high-data devices like video monitors, laptops, and tablets.

* That speed is 67 times higher than the current 802.11n WiFi system’s max theoretical speed of 600Mbps capacity — which has to be shared between users, so the ratio is actually about 100 times, according to TU/e researchers. That speed is also 16 times higher than the 2.5 Gbps performance with the best (802.11ac) Wi-Fi system — which also has to be shared (so actually lower) — and in addition, uses the 5GHz wireless band, which has limited range. “The theoretical max speed of 802.11ac is eight 160MHz 256-QAM channels, each of which are capable of 866.7Mbps, for a total of 6,933Mbps, or just shy of 7Gbps,” notes Extreme Tech. “In the real world, thanks to channel contention, you probably won’t get more than two or three 160MHz channels, so the max speed comes down to somewhere between 1.7Gbps and 2.5Gbps. Compare this with 802.11n’s max theoretical speed, which is 600Mbps.”

** The TU/e system was designed by Joanne Oh as a doctoral thesis and part of the wider BROWSE project headed up by professor of broadband communication technology Ton Koonen, with funding from the European Research Council, under the auspices of the noted TU/e Institute for Photonic Integration.


*** According to TU/e researchers, a few other groups are investigating network concepts in which infrared-light rays are directed using movable mirrors. The disadvantage here is that this requires active control of the mirrors and therefore energy, and each mirror is only capable of handling one ray of light at a time. The grating used the and Oh can cope with many rays of light and, therefore, devices at the same time.

Genetic history of indigenous peoples of the Americas

From Wikipedia, the free encyclopedia

Possible migration routes to the Americas as predicted by the distribution of Y-DNA haplogroups: inland route (purple lines), Pacific coastal route (brown dashed line), and possible trans-Atlantic route (light blue double line).

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 in 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 Amerindians groups are derived from a basal Ancestral lineage, which formed in Siberia prior to the Last Glacial Maximum, between about 36,000 and 25,000 years ago, from a combination of early East Asian and Ancient North Eurasian ancestry and which 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).^[4]
In the early 2000s, archaeogenetics was primarily based on Human Y-chromosome DNA haplogroups and Human mitochondrial DNA haplogroups.^[5] Autosomal "atDNA" markers are also used, but differ from mtDNA or Y-DNA in that they overlap significantly.^[6]

Analyses of genetics among Amerindian and Siberian populations have been used to argue for early isolation of founding populations on Beringia^[7] and for later, more rapid migration from Siberia through Beringia into the New World.^[8] The microsatellite diversity and distributions of the Y lineage specific to South America indicates that certain Amerindian populations have been isolated since the initial colonization of the region.^[9] 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.^[10][11][12] This suggests that the peoples who first settled the northern extremes of North America and Greenland derived from later migrant populations than those who penetrated farther south in the Americas.^[13][14] Linguists and biologists have reached a similar conclusion based on analysis of Amerindian language groups and ABO blood group system distributions.^[15][16][17]

Autosomal DNA

Genetic groups according to Tribal DNA  

  1. Arctic

  2. Salishan

  3. Athabaskan

  4. North Amerindian

  5. Ojibwa

  6. Mexica

  7. Maya

  8. Chibcha

  9. Andean

  10. Amazonian

  11. Gran Chaco

  12. Patagonian

Genetic diversity and population structure in the American landmass is also done 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.^[18][19] The Amerindian populations show a lower genetic diversity than populations from other continental regions.^[19] 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).^[18][19] 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.^[18][19] 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.^[18]

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 a factor of 10 over 800 – 1000 years.^[20][21] The data also shows that there have been genetic exchanges between Asia, the Arctic, and Greenland since the initial peopling of the Americas.^[21][22]

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.^[4]

In 2014, the autosomal DNA of a 12,500+-year-old infant from Montana was sequenced.^[23] 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.^[24]

According to an autosomal genetic study from 2012,^[25] Native Americans descend of 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. ^[25]

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.^{[clarification needed][26]}

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.^[27][28][29]

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.^[30]

Membership in haplogroups Q and C3b implies indigenous American patrilineal descent.^[31]

Haplogroup Q

Spread of Haplogroup Q in indigenous populations.

Q-M242 (mutational name) is the defining (SNP) of Haplogroup Q (Y-DNA) (phylogenetic name). Within the Q clade, there are 14 haplogroups marked by 17 SNPs.^2009[32][33] 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.^[34] The Ket are thought to be the only survivors of ancient wanderers living in Siberia.^[20] Their population size is very small; there are fewer than 1,500 Ket in Russia.^2002[20] The Selkup have a slightly larger population size than the Ket, with approximately 4,250 individuals.^[35]

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.^[11] A member of this initial population underwent a mutation, which defines its descendant population, known by the Q-M3 (SNP) mutation.^[36] These descendants migrated all over the Americas.^[32]

Haplogroup Q-M3 is defined by the presence of the rs3894 (M3) (SNP).^[1][20][37] The Q-M3 mutation is roughly 15,000 years old as that is when the initial migration of Paleo-Indians into the Americas occurred.^[38][39] Q-M3 is the predominant haplotype in the Americas, at a rate of 83% in South American populations,^[9] 50% in the Na-Dené populations, and in North American Eskimo-Aleut populations at about 46%.^[34] 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.^[34][40][18]
 

Y chromosome R haplogroup among Native Americans (right; Malhi et al., 2008), and population density mapping (left) indicate a non-correlation between haplogroup R frequency and population density. The study of Malhi et al. 2008 suggest European admixture has resulted in a decreasing gradient of haplogroup R in Native Americans.^[41]

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.^[9] M19 has been detected in (59%) of Amazonian Ticuna men and in (10%) of Wayuu men.^[9] Subclade M19 appears to be unique to South American Indigenous peoples, arising 5,000 to 10,000 years ago.^[9] This suggests that population isolation and perhaps even the establishment of tribal groups began soon after migration into the South American areas.^[20][42] 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.

The principal-component analysis suggests a close genetic relatedness between some North American Amerindians (the Chipewyan and the Cheyenne) and certain populations of central/southern Siberia (particularly the Kets, Yakuts, Selkups, and Altays), at the resolution of major Y-chromosome haplogroups.^[9] This pattern agrees with the distribution of mtDNA haplogroup X, which is found in North America, is absent from eastern Siberia, but is present in the Altais of southern central Siberia. Similarly, the Asian populations closest to Native Americans are characterized by a predominance of lineage P-M45* and low frequencies of C-RPS4Y.^[9]

Haplogroup R1

Spread of Haplogroup R in Indigenous populations.

Haplogroup R1 (Y-DNA) (specifically R1b) is the second most predominant Y haplotype found among indigenous Amerindians after Q (Y-DNA).^[41] The distribution of R1 is believed by some to be associated with the re-settlement of Eurasia following the last glacial maximum. One theory put forth is that R1 entered the Americas with the initial founding population,^[9] suggesting prehistoric Amerindian immigration from Asia through Beringia^[43][44] and correlating mostly with the frequency of haplogroups Q-M3 and P-M45*.^[9] A second theory is that it was introduced during European colonization.^[41] 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%).^[41]

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."^[44] 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."^[45]

Haplogroup C-P39

Spread of Haplogroup C-M217 in Indigenous populations.

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 commonly found in today's Na-Dené speakers, with the highest frequency found among the Athabaskans at 42%.^[11] This distinct and isolated branch C-P39 includes almost all the Haplogroup C-M217 Y-chromosomes found among all indigenous peoples of the Americas.^[46] The Na-Dené groups are also unusual among indigenous peoples of the Americas in having a relatively high frequency of Q-M242 (25%).^[34]

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.^[11][10][47]

Maternal lineages

Schematic illustration of maternal (mtDNA) gene-flow in and out of Beringia, from 25,000 years ago to present.

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.^[48] As a whole, the greatest frequency of the four Amerindian associated haplogroups occurs in the Altai-Baikal region of southern Siberia.^[49] Some subclades of C and D closer to the Amerindian subclades occur among Mongolian, Amur, Japanese, Korean, and Ainu populations.^[48][50]

When studying human mitochondrial DNA (mtDNA) haplogroups, the results indicated until recently^{[year needed]} 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.^{[51] [52]} All indigenous Amerindian mtDNA can be traced back to five haplogroups, A, B, C, D and X.^[53][54] More specifically, indigenous Amerindian mtDNA belongs to sub-haplogroups A2, B2, C1, D1, and X2a (with minor groups C4c, D2, D3, and D4h3).^[7][52] 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.^[53] The remaining 5% is composed of the X2a, D2, D3, C4, and D4h3 sub-haplogroups.^[52][53]

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.^[20] 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.^[20] However, X2a is a major mtDNA subclade in North America; among the Algonquian peoples, it comprises up to 25% of mtDNA types.^[1][55] 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%).^[56] Haplogroup X is more strongly present in the Near East, the Caucasus, and Mediterranean Europe.^[56] 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.^{[57][58][59][60]}

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.^[61] This suggests that the colonizers of the far north, and subsequently Greenland, originated from later coastal populations.^[61] Then a genetic exchange in the northern extremes introduced by the Thule people (proto-Inuit) approximately 800–1,000 years ago began.^[12][62] 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.^[12][62]
 

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"^[44] "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."^[63]

A route through Beringia is seen as more likely than the Solutrean hypothesis.^[64] 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."^[65]

Another study, also focused on the mtDNA (that which is inherited through only the maternal line),^[7] 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".^[66]

Paleoamericans

There is genetic evidence for an early wave of migration to the Americas. It is uncertain whether this "Paleoamerican" (also "Paleoamerind", not to 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.^[67] Genetic evidence for "Paleoamerinds" consists of the presence of apparent admixture of archaic Sundadont lineages to the remote populations in the South American rainforest and in, and in the genetics and cranial morphology of Patagonians-Fuegians. ^[68] Nomatto et al. (2009) proposed 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.^[69] Evidence of people from Australia and Melanesia admixture in Amazonian populations was found by Skoglund and Reich (2016).^[70] Archaeological evidence for pre-LGM human presence in the Americas was first presented in the 1970s.^[71][72] notably the "Luzia Woman" skull found in Brazil and the Monte Verde site in Chile, both discovered in 1975.^[73]

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.^[74][75]

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.^[76]

Many individuals who self-identify as one race exhibit genetic evidence of a multiracial ancestry.^[77] 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).^{[78][unreliable source]} The new soldier-settlers fathered children with Amerindian women and later with African slaves.^{[79][unreliable source]} These mixed-race children were generally identified by the Spanish colonist and Portuguese colonist as "Castas".^[80]

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.^[81] 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.^[82]

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.^[83] In the United States 2010 census, nearly 3 million people indicated that their race was Native American (including Alaska Native).^[84] 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,^[85] a phenomenon dubbed the "Cherokee Syndrome".^[86] The context is the cultivation of an opportunistic ethnic identity related to the preceived prestige associated with Native American ancestry.^[87] Native American identity in the Eastern United States is mostly detached from genetic descent, and embraced by people of predominantly European ancestry.^[87][88] Some tribes have adopted criteria of racial purity, 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,^[89]

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.^[90][91] 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.^[92] 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.^[93]

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.^[91] 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.^[94] 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%.^[94] In indigenous North American populations the frequency of type "A" ranges from 16% to 82%.^[94] This suggests again that the initial Amerindians evolved from an isolated population with a minimal number of individuals.

Scientists reverse aging in mice by repairing damaged DNA

Could lead to an anti-aging drug that counters damage from old age, cancer, and radiation

March 26, 2017
Original link:  http://www.kurzweilai.net/scientists-reverse-aging-in-mice-by-repairing-damaged-dna

A research team led by Harvard Medical School professor of genetics David Sinclair, PhD, has made a discovery that could lead to a revolutionary new drug that allows cells to repair DNA damaged by aging, cancer, and radiation.

In a paper published in the journal Science on Friday (March 24), the scientists identified a critical step in the molecular process related to DNA damage.

The researchers found that a compound known as NAD (nicotinamide adenine dinucleotide), which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. In an experiment, they found that treating mice with a NAD+ precursor called NMN (nicotinamide mononucleotide) improved their cells’ ability to repair DNA damage.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said senior author Sinclair.

Disarming a rogue agent: When the NAD molecule (red) binds to the DBC1 protein (beige), it prevents DBC1 from attaching to and incapacitating a protein (PARP1) that is critical for DNA repair. (credit: David Sinclair)

Human trials of NMN therapy will begin within the next few months to “see if these results translate to people,” he said. A safe and effective anti-aging drug is “perhaps only three to five years away from being on the market if the trials go well.”

What it means for astronauts, childhood cancer survivors, and the rest of us

The researchers say that in addition to reversing aging, the DNA-repair research has attracted the attention of NASA. The treatment could help deal with radiation damage to astronauts in its Mars mission, which could cause muscle weakness, memory loss, and other symptoms (see “Mars-bound astronauts face brain damage from galactic cosmic ray exposure, says NASA-funded study“), and more seriously, leukemia cancer and weakened immune function (see “Travelers to Mars risk leukemia cancer, weakend immune function from radiation, NASA-funded study finds“).

The treatment could also help travelers aboard aircraft flying across the poles. A 2011 NASA study showed that passengers on polar flights receive about 12 percent of the annual radiation limit recommended by the International Committee on Radiological Protection.

The other group that could benefit from this work is survivors of childhood cancers, who are likely to suffer a chronic illness by age 45, leading to accelerated aging, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer, the researchers noted.

For the past four years, Sinclair’s team has been working with spinoff MetroBiotech on developing NMN as a drug. Sinclair previously made a link between the anti-aging enzyme SIRT1 and resveratrol. “While resveratrol activates SIRT1 alone, NAD boosters [like NMN] activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.

Sinclair is also a professor at the University of New South Wales School of Medicine in Sydney, Australia.

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Abstract of A conserved NAD⁺ binding pocket that regulates protein-protein interactions during aging

DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD⁺ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD⁺ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD⁺ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD⁺. Thus, NAD⁺ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.

References:

• Jun Li, Michael S. Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A. Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair. A conserved NAD binding pocket that regulates protein-protein interactions during aging. Science, 24 Mar 2017: Vol. 355, Issue 6331, pp. 1312-1317 DOI: 10.1126/science.aad8242