90-525: Matthew Stanley Meselson (born May 24, 1930) is a geneticist and molecular biologist currently at Harvard University , known for his demonstration, with Franklin Stahl , of semi-conservative DNA replication . After completing his Ph.D. under Linus Pauling at the California Institute of Technology , Meselson became a Professor at Harvard University in 1960, where he has remained today as Professor of
180-538: A chromoprotein , and globulin . In mammals , hemoglobin makes up about 96% of a red blood cell's dry weight (excluding water), and around 35% of the total weight (including water). Hemoglobin has an oxygen-binding capacity of 1.34 mL of O 2 per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood plasma alone. The mammalian hemoglobin molecule can bind and transport up to four oxygen molecules. Hemoglobin also transports other gases. It carries off some of
270-441: A coordinate covalent bond , completing the octahedral group of six ligands. This reversible bonding with oxygen is why hemoglobin is so useful for transporting oxygen around the body. Oxygen binds in an "end-on bent" geometry where one oxygen atom binds to Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted octahedron . Even though carbon dioxide
360-466: A 1983 field study in Thailand; the inability of US and UK government laboratories to corroborate initial reports of the presence of trichothecene mycotoxins in samples of the alleged agent and in biomedical samples from alleged victims; the lack of any supporting evidence from extensive interviews with Vietnamese military defectors and prisoners; and other considerations, Meselson and his colleagues argued that
450-593: A UK proposal for an international ban, Meselson was among those who successfully advocated international agreements to ban biological and then chemical weapons, leading to the Biological Weapons Convention of 1972 and the Chemical Weapons Convention of 1993. Meselson and his colleagues have undertaken three on-site investigations with implications for chemical and biological weapons arms control. During August and September 1970, on behalf of
540-459: A conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the α-amino group. Carbon dioxide binds to hemoglobin and forms carbaminohemoglobin . This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the Bohr effect . The Bohr effect favors the T state rather than
630-624: A consultant to various US government agencies and through the Harvard Sussex Program , an academic research organization based at Harvard and at the University of Sussex in the UK of which he and Julian Perry Robinson in the UK are co-directors. Concluding that biological weapons served no substantial military purpose for the US and that their proliferation would pose a serious threat and that, in years ahead,
720-420: A decrease in blood pH. Ventilation , or breathing, may reverse this condition by removal of carbon dioxide , thus causing a shift up in pH. Hemoglobin exists in two forms, a taut (tense) form (T) and a relaxed form (R). Various factors such as low pH, high CO 2 and high 2,3 BPG at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely,
810-469: A dimer made up of identical globin subunits, which then evolved to assemble into a tetrameric architecture after the duplication. The development of α and β genes created the potential for hemoglobin to be composed of multiple distinct subunits, a physical composition central to hemoglobin's ability to transport oxygen. Having multiple subunits contributes to hemoglobin's ability to bind oxygen cooperatively as well as be regulated allosterically. Subsequently,
900-407: A high pH, low CO 2 , or low 2,3 BPG favors the relaxed form, which can better bind oxygen. The partial pressure of the system also affects O 2 affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state
990-491: A phosphate "pocket" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity. GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra hydrogen bond formed that further stabilizes the tense state. Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity. A variant hemoglobin, called fetal hemoglobin (HbF, α 2 γ 2 ),
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#17328527766241080-677: A process that enables cells to correct mistakes in replicating DNA. Meselson's current research is aimed at understanding the advantage of sexual reproduction in evolution. Meselson and his colleagues have recently demonstrated that Bdelloid rotifers do, in fact, engage in sexual reproduction employing meiosis of an atypical sort. In 1963 Meselson served as a resident consultant in the US Arms Control and Disarmament Agency , where he became interested in chemical and biological weapons programs and policies. Since then he has been involved in chemical and biological weapons defense and disarmament matters as
1170-512: A set of alpha-helix structural segments connected together in a globin fold arrangement. Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as myoglobin . This folding pattern contains a pocket that strongly binds the heme group. A heme group consists of an iron (Fe) ion held in a heterocyclic ring, known as a porphyrin . This porphyrin ring consists of four pyrrole molecules cyclically linked together (by methine bridges) with
1260-482: A variety of jobs. There are many careers for geneticists in medicine , agriculture , wildlife , general sciences, or many other fields. Listed below are a few examples of careers a geneticist may pursue. Hemoglobin Hemoglobin ( haemoglobin , Hb or Hgb ) is a protein containing iron that facilitates the transportation of oxygen in red blood cells . Almost all vertebrates contain hemoglobin, with
1350-506: Is diamagnetic , whereas both oxygen and high-spin iron(II) are paramagnetic . Experimental evidence strongly suggests heme iron is in the iron(III) oxidation state in oxyhemoglobin, with the oxygen existing as superoxide anion (O 2 ) or in a covalent charge-transfer complex. Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of
1440-475: Is a colorless, odorless and tasteless gas, and poses a potentially fatal threat, carbon monoxide detectors have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin , which may cause the skin of CO poisoning victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%, headache and nausea occur; if
1530-450: Is a higher offspring survival rate among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower for women with higher hemoglobin-oxygen affinity when compared to the mortality rate of offspring from women with low hemoglobin-oxygen affinity. While the exact genotype and mechanism by which this occurs
1620-473: Is bound to amino groups of the globin proteins to form carbaminohemoglobin ; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals. Nitric oxide can also be transported by hemoglobin; it is bound to specific thiol groups in the globin protein to form an S-nitrosothiol, which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues
1710-420: Is called the root effect . This is seen in bony fish. It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O 2 in lungs), and efficient in unloading (unloading O 2 in tissues). In people acclimated to high altitudes, the concentration of 2,3-Bisphosphoglycerate (2,3-BPG) in
1800-423: Is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the amine groups of the protein chains attached to the heme groups. The iron ion may be either in the ferrous Fe or in the ferric Fe state, but ferrihemoglobin ( methemoglobin ) (Fe ) cannot bind oxygen. In binding, oxygen temporarily and reversibly oxidizes (Fe ) to (Fe ) while oxygen temporarily turns into
1890-412: Is denoted as α 2 β 2 . The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 16,000 daltons , for a total molecular weight of the tetramer of about 64,000 daltons (64,458 g/mol). Thus, 1 g/dL=0.1551 mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules. In human infants, the fetal hemoglobin molecule
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#17328527766241980-430: Is favoured. Additionally, the binding of oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative). Classically, the iron in oxyhemoglobin is seen as existing in the iron(II) oxidation state. However, the complex of oxygen with heme iron
2070-444: Is found in the developing fetus , and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the placenta is able to take oxygen from maternal blood. Hemoglobin also carries nitric oxide (NO) in
2160-467: Is hypothesized to assist oxygen transport in tissues, by releasing vasodilatory nitric oxide to tissues in which oxygen levels are low. The binding of oxygen is affected by molecules such as carbon monoxide (for example, from tobacco smoking , exhaust gas , and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin's binding affinity for CO is 250 times greater than its affinity for oxygen, Since carbon monoxide
2250-455: Is made up of 2 α chains and 2 γ chains. The γ chains are gradually replaced by β chains as the infant grows. The four polypeptide chains are bound to each other by salt bridges , hydrogen bonds , and the hydrophobic effect . In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin). Oxyhemoglobin is formed during physiological respiration when oxygen binds to
2340-426: Is not yet clear, selection is acting on these women's ability to bind oxygen in low partial pressures, which overall allows them to better sustain crucial metabolic processes. Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in
2430-545: Is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient nitric oxide dioxygenase function of globins. Carbon di oxide occupies a different binding site on the hemoglobin. At tissues, where carbon dioxide concentration is higher, carbon dioxide binds to allosteric site of hemoglobin, facilitating unloading of oxygen from hemoglobin and ultimately its removal from
2520-399: Is tasked with oxygen transport. The α- and β-like globin genes encode the individual subunits of the protein. The predecessors of these genes arose through another duplication event also after the gnathosome common ancestor derived from jawless fish, approximately 450–500 million years ago. Ancestral reconstruction studies suggest that the preduplication ancestor of the α and β genes was
2610-466: Is weakly attracted to magnetic fields . In contrast, oxygenated hemoglobin exhibits diamagnetism , a weak repulsion from a magnetic field. Scientists agree that the event that separated myoglobin from hemoglobin occurred after lampreys diverged from jawed vertebrates . This separation of myoglobin and hemoglobin allowed for the different functions of the two molecules to arise and develop: myoglobin has more to do with oxygen storage while hemoglobin
2700-533: The Harvard faculty in 1960. In 1957, Meselson and Franklin Stahl (as part of the phage group ) showed that DNA replicates semi-conservatively. In order to test hypotheses for how DNA replicates, Meselson and Stahl, together with Jerome Vinograd , invented a method that separates macromolecules according to their buoyant density. The method, equilibrium density gradient centrifugation, was sufficiently sensitive that Meselson and Stahl were able to separate DNA containing
2790-520: The Lasker Award for Special Achievement in Medical Science. His laboratory at Harvard currently investigates the biological and evolutionary nature of sexual reproduction, genetic recombination, and aging. Many of his past students are notable biologists, including Nobel Laureate Sidney Altman , as well as Mark Ptashne , Susan Lindquist , Stephen F. Heinemann , and Richard I. Morimoto . Meselson
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2880-517: The Pleistocene . This was also found in hummingbirds that inhabit the Andes. Hummingbirds already expend a lot of energy and thus have high oxygen demands and yet Andean hummingbirds have been found to thrive in high altitudes. Non-synonymous mutations in the hemoglobin gene of multiple species living at high elevations ( Oreotrochilus, A. castelnaudii, C. violifer, P. gigas, and A. viridicuada ) have caused
2970-734: The University of Chicago , Pauling immediately asked him to come to Caltech to begin graduate studies with him, to which Meselson agreed. As a graduate student of Linus Pauling in chemistry at the California Institute of Technology (1953-1957), Meselson's doctoral dissertation was on equilibrium density gradient centrifugation and on x-ray crystallography . Besides Pauling, Meselson's dissertation committee also included Jerome Vinograd , Richard Feynman , and Harden M. McConnell . Meselson then served as Assistant Professor of Physical Chemistry and then Senior Research Fellow at Caltech until he joined
3060-893: The inheritance of biological traits. A basic science geneticist is a scientist who usually has earned a PhD in genetics and undertakes research and/or lectures in the field. A medical geneticist is a physician who has been trained in medical genetics as a specialization and evaluates, diagnoses, and manages patients with hereditary conditions or congenital malformations ; and provides genetic risk calculations and mutation analysis . Geneticists participate in courses from many areas, such as biology , chemistry , physics , microbiology , cell biology , bioinformatics , and mathematics . They also participate in more specific genetics courses such as molecular genetics , transmission genetics, population genetics , quantitative genetics , ecological genetics , epigenetics , and genomics . Geneticists can work in many different fields, doing
3150-597: The superoxide ion, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe is protonated, the hemoglobin iron will remain oxidized and incapable of binding oxygen. In such cases, the enzyme methemoglobin reductase will be able to eventually reactivate methemoglobin by reducing the iron center. In adult humans, the most common hemoglobin type is a tetramer (which contains four subunit proteins) called hemoglobin A , consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This
3240-434: The vasculature (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). Hemoglobin has a quaternary structure characteristic of many multi-subunit globular proteins. Most of the amino acids in hemoglobin form alpha helices , and these helices are connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within
3330-420: The 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. This difference is used for the measurement of the amount of oxygen in a patient's blood by an instrument called a pulse oximeter . This difference also accounts for the presentation of cyanosis , the blue to purplish color that tissues develop during hypoxia . Deoxygenated hemoglobin is paramagnetic ; it
3420-573: The American Association for the Advancement of Science, Meselson led a team in the Republic of Vietnam in a pilot study of the ecological and health effects of the military use of herbicides. Upon returning to Harvard, he and Robert Baughman developed an advanced mass-spectrometric method for analysis of the toxic herbicide contaminant dioxin and applied it to environmental and biomedical samples from
3510-944: The American Philosophical Society, the Académie des Sciences (Paris), the Royal Society (London) and the Russian Academy of Sciences and has received numerous awards and honors in the field of science and in public affairs. He has served on the Council of the National Academy of Sciences, the Council of the Smithsonian Institution, the Arms Control and Non-Proliferation Advisory Board to the US Secretary of State and
3600-530: The CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO. In similar fashion, hemoglobin also has competitive binding affinity for cyanide (CN ), sulfur monoxide (SO), and sulfide (S ), including hydrogen sulfide (H 2 S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity. The iron atom in
3690-893: The Committee on International Security and Arms Control of the US National Academy of Sciences. He is past President of the Federation of American Scientists, and presently is co-director of the Harvard Sussex Program on Chemical and Biological Weapons and a member of the board of directors of the Belfer Center for Science and International Affairs at the John F. Kennedy School of Government at Harvard University. He married three times, first to Katherine Kaynis, then to Sarah Page, with whom he had two daughters, Amy and Zoe. His third marriage
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3780-472: The DNA was seen to have a density halfway between that of N DNA and N DNA. In successive generations, the fraction of DNA that was "half-heavy" fell by a factor of ½, as the total amount of DNA increased two-fold. When the half-heavy DNA was made single stranded by heating, it separated into two density species, one heavy (containing only N) and one light (containing only N). The experiment implied that, upon replication,
3870-482: The Natural Sciences. In the famous Meselson–Stahl experiment of 1958 he and Frank Stahl demonstrated through nitrogen isotope labeling that DNA is replicated semi-conservatively. In addition, Meselson, François Jacob , and Sydney Brenner discovered the existence of messenger RNA in 1961. Meselson has investigated DNA repair in cells and how cells recognize and destroy foreign DNA, and, with Werner Arber ,
3960-405: The R state. (shifts the O 2 -saturation curve to the right ). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH
4050-615: The Vietnam and the US. In December 1970, President Richard Nixon ordered a "rapid but orderly" phase-out of herbicide operations in Vietnam. During the 1980s, Meselson investigated allegations that " yellow rain " was a Soviet toxin weapon being used against Hmong tribespeople in Laos. Citing the physical appearance and high pollen content of samples of the alleged agent; the resemblance of the alleged attacks to showers of feces from swarms of honeybees that he and entomologist Thomas Seeley documented during
4140-894: The acquisition of biological agents for hostile purposes, which in 1972 became known as the Biological Weapons Convention . Meselson has received the Award in Molecular Biology from the National Academy of Sciences , the Public Service Award of the Federation of American Scientists , the Presidential Award of the New York Academy of Sciences , the 1995 Thomas Hunt Morgan Medal of the Genetics Society of America, as well as
4230-523: The allegations were mistaken. In April 1980 Meselson served as a resident consultant to the CIA investigating a major outbreak of anthrax among people in the Soviet city of Sverdlovsk. He concluded that on the basis of available evidence the official Soviet explanation that the outbreak was caused by consumption of meat from infected cattle was plausible but that there should be an independent on-site investigation. After
4320-542: The beta subunit is coded by gene HBB on chromosome 11. The amino acid sequences of the globin subunits usually differ between species, with the difference growing with evolutionary distance. For example, the most common hemoglobin sequences in humans, bonobos and chimpanzees are completely identical, with exactly the same alpha and beta globin protein chains. Human and gorilla hemoglobin differ in one amino acid in both alpha and beta chains, and these differences grow larger between less closely related species. Mutations in
4410-420: The binding of oxygen to the remaining three monomers' heme groups, thus saturating the hemoglobin molecule with oxygen. In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a cooperative process . The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for
4500-402: The blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension . This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a heterotropic allosteric effect. Hemoglobin in organisms at high altitudes has also adapted such that it has less of an affinity for 2,3-BPG and so
4590-468: The body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the Bohr effect . Through the enzyme carbonic anhydrase , carbon dioxide reacts with water to give carbonic acid , which decomposes into bicarbonate and protons : Hence, blood with high carbon dioxide levels is also lower in pH (more acidic ). Hemoglobin can bind protons and carbon dioxide, which causes
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#17328527766244680-564: The body's respiratory carbon dioxide (about 20–25% of the total) as carbaminohemoglobin , in which CO 2 binds to the heme protein . The molecule also carries the important regulatory molecule nitric oxide bound to a thiol group in the globin protein, releasing it at the same time as oxygen. Hemoglobin is also found in other cells, including in the A9 dopaminergic neurons of the substantia nigra , macrophages , alveolar cells , lungs, retinal pigment epithelium, hepatocytes, mesangial cells of
4770-527: The collapse of the Soviet Union, he was allowed to bring a team to Sverdlovsk in 1992 and again in 1993. Their reports conclusively showed that the official Soviet explanation was wrong and that the outbreak was caused by the release of an anthrax aerosol at a military biological facility in the city. Meselson is a member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences,
4860-426: The cytosol. Production of Hb continues in the cell throughout its early development from the proerythroblast to the reticulocyte in the bone marrow . At this point, the nucleus is lost in mammalian red blood cells, but not in birds and many other species. Even after the loss of the nucleus in mammals, residual ribosomal RNA allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering
4950-662: The density gradient method to studies of genetic recombination in the bacteriophage Lambda. The question was whether such recombination involved breakage of the recombining DNA molecules or cooperative synthesis of new molecules. The question could be answered by examining phage particles derived from co-infection of bacteria with genetically marked Lambda phages that were labeled with heavy isotopes (C and N). The density-gradient method allowed individual progeny phages to be characterized for their inheritance of parental DNA and of parental genetic makers. Meselson's initial demonstration of breakage-associated, replication-independent recombination
5040-560: The exploitation of advanced biology for hostile purposes would be inimical to society generally, he worked to persuade members of the Executive Branch, the Congress and the public that the US had no need for such weapons and that there would be benefits in renouncing them and working for worldwide prohibition. After President Richard Nixon in 1969 canceled the US BW offensive program and endorsed
5130-419: The field for the decade from 1973 to 1983. In 1961, Sydney Brenner , François Jacob and Meselson used the density-gradient method to demonstrate the existence of messenger RNA. In subsequent work, Meselson and his students demonstrated the enzymatic basis of host-directed restriction, a process by which cells recognize and destroy foreign DNA and then predicted and demonstrated methyl-directed mismatch repair,
5220-403: The genes for hemoglobin can result in variants of hemoglobin within a single species, although one sequence is usually "most common" in each species. Many of these mutations cause no disease, but some cause a group of hereditary diseases called hemoglobinopathies . The best known hemoglobinopathy is sickle-cell disease , which was the first human disease whose mechanism was understood at
5310-409: The globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting S-nitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO
5400-505: The heavy isotope of nitrogen, N, from DNA made of the lighter isotope, N. In their classic experiment, described and analyzed in a book by science historian Frederic L. Holmes, they grew the bacterium Escherichia coli for many generations in medium containing N as the only nitrogen source and then switched the bacteria to growth medium containing N instead. They extracted DNA from bacteria prior to switching and, at intervals, for several generations thereafter. After one generation of growth, all
5490-399: The heme component of the protein hemoglobin in red blood cells. This process occurs in the pulmonary capillaries adjacent to the alveoli of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized as a terminal electron acceptor in the production of ATP by the process of oxidative phosphorylation . It does not, however, help to counteract
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#17328527766245580-401: The heme group must initially be in the ferrous (Fe ) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the ferric (Fe ) state without oxygen converts hemoglobin into "hem i globin" or methemoglobin , which cannot bind oxygen. Hemoglobin in normal red blood cells
5670-574: The higher pressures at sea level. Recent studies of deer mice found mutations in four genes that can account for differences between high- and low-elevation populations. It was found that the genes of the two breeds are "virtually identical—except for those that govern the oxygen-carrying capacity of their hemoglobin. . . . The genetic difference enables highland mice to make more efficient use of their oxygen." Mammoth hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during
5760-400: The iron complex, it causes the iron atom to move back toward the center of the plane of the porphyrin ring (see moving diagram). At the same time, the imidazole side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in
5850-425: The iron ion bound in the center. The iron ion, which is the site of oxygen binding, coordinates with the four nitrogen atoms in the center of the ring, which all lie in one plane. The heme is bound strongly (covalently) to the globular protein via the N atoms of the imidazole ring of F8 histidine residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by
5940-709: The kidney, endometrial cells, cervical cells, and vaginal epithelial cells. In these tissues, hemoglobin absorbs unneeded oxygen as an antioxidant , and regulates iron metabolism . Excessive glucose in the blood can attach to hemoglobin and raise the level of hemoglobin A1c. Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. In these organisms, hemoglobins may carry oxygen, or they may transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant called leghemoglobin serves to scavenge oxygen away from anaerobic systems such as
6030-513: The molecular level. A mostly separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation . All these diseases produce anemia . Variations in hemoglobin sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to the thin air at high altitudes, where lower partial pressure of oxygen diminishes its binding to hemoglobin compared to
6120-487: The molecular mass of hemoglobin to n × 16000 ( n =number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a protein's molecular mass. This "hasty conclusion" drew ridicule from colleagues who could not believe that any molecule could be so large. However, Gilbert Smithson Adair confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions. Although blood had been known to carry oxygen since at least 1794,
6210-431: The molecule, which then causes each polypeptide chain to fold into a specific shape. Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement. In most vertebrates, the hemoglobin molecule is an assembly of four globular protein subunits. Each subunit is composed of a protein chain tightly associated with a non-protein prosthetic heme group. Each protein chain arranges into
6300-411: The next ones, in a way favorable for binding. This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence,
6390-441: The nitrogen-fixing nodules of leguminous plants, preventing oxygen poisoning. The medical condition hemoglobinemia , a form of anemia , is caused by intravascular hemolysis , in which hemoglobin leaks from red blood cells into the blood plasma . In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron, he calculated
6480-553: The oxygen binding curve of hemoglobin is sigmoidal , or S -shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding. The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency resonance has been discussed. Besides the oxygen ligand , which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include competitive inhibitors such as carbon monoxide (CO) and allosteric ligands such as carbon dioxide (CO 2 ) and nitric oxide (NO). The carbon dioxide
6570-414: The oxygen-carrying property of hemoglobin was described by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation
6660-466: The pedagogical approach in most of the courses he took. He enrolled, however, in Linus Pauling 's freshman chemistry course, which he loved, and worked on a project for Pauling the same year on hemoglobin structure. Meselson subsequently returned to the University of Chicago for a year to enroll in courses in chemistry, physics, and math, though he did not receive another degree. The following year, he
6750-441: The protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier. As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes
6840-491: The protein to have less of an affinity for inositol hexaphosphate (IHP), a molecule found in birds that has a similar role as 2,3-BPG in humans; this results in the ability to bind oxygen in lower partial pressures. Birds' unique circulatory lungs also promote efficient use of oxygen at low partial pressures of O 2 . These two adaptations reinforce each other and account for birds' remarkable high-altitude performance. Hemoglobin adaptation extends to humans, as well. There
6930-410: The protein will be shifted more towards its R state. In its R state, hemoglobin will bind oxygen more readily, thus allowing organisms to perform the necessary metabolic processes when oxygen is present at low partial pressures. Animals other than humans use different molecules to bind to hemoglobin and change its O 2 affinity under unfavorable conditions. Fish use both ATP and GTP . These bind to
7020-433: The protein's chemical properties and function. The amino acid sequence of any polypeptide is translated from a segment of DNA, the corresponding gene . There is more than one hemoglobin gene. In humans, hemoglobin A (the main form of hemoglobin in adults) is coded by genes HBA1 , HBA2 , and HBB . Alpha 1 and alpha 2 subunits are respectively coded by genes HBA1 and HBA2 close together on chromosome 16, while
7110-528: The registrar at his high school, however, he was informed that in order to receive his high school diploma, he needed three full years of physical education, which he lacked. After searching for options, he enrolled at the University of Chicago at the age of 16 in 1946 intending to study chemistry, since it did not require a high school diploma to attend. At the University of Chicago , Meselson studied liberal arts including history and classics as an undergraduate from 1946 to 1949 after realizing upon arriving that
7200-412: The sole exception of the fish family, Channichthyidae . Hemoglobin in the blood carries oxygen from the respiratory organs ( lungs or gills ) to the other tissues of the body, where it releases the oxygen to enable aerobic respiration which powers an animal's metabolism . A healthy human has 12 to 20 grams of hemoglobin in every 100 mL of blood. Hemoglobin is a metalloprotein ,
7290-474: The two complementary strands of the bacterial DNA separate, and that each of the single strands directs the synthesis of a new, complementary strand, a result that verified the suggestion for DNA replication put forward five years earlier by James Watson and Francis Crick and lent important early support for the Watson-Crick model of the DNA molecule. In collaboration with Jean Weigle , Meselson then applied
7380-545: The university had abolished bachelor's degrees in specialized field such as chemistry and physics. After completing his studies, Meselson spent half a year traveling in Europe. where he spent most of his time reading and making friends. The devastation of the war was still evident in Europe in 1949, as were the beginning tensions of the Cold War . The following year, Meselson returned to Caltech to begin freshman studies again, but disliked
7470-452: The α gene also underwent a duplication event to form the HBA1 and HBA2 genes. These further duplications and divergences have created a diverse range of α- and β-like globin genes that are regulated so that certain forms occur at different stages of development. Most ice fish of the family Channichthyidae have lost their hemoglobin genes as an adaptation to cold water. When oxygen binds to
7560-519: Was accepted into a graduate physics program at the University of California at Berkeley where he remained for a year. In the summer of 1953, Meselson was at a swimming pool party at the Pauling home in Sierra Madre (he was friends with Pauling's son Peter and with his daughter Linda), and Pauling asked him what he intended to do the following year. Upon hearing Meselson respond that he intended to return to
7650-555: Was born in Denver, Colorado, on May 24, 1930, and attended elementary and high school in Los Angeles, California. While a young child he was interested in chemistry and physics, and conducted many experiments in the natural sciences at home. During World War II , Meselson attended summer school during summer vacations and received enough high school credits to graduate a year and a half ahead of time. When he attempted to acquire his diploma from
7740-455: Was described a few years later by Felix Hoppe-Seyler . With the development of X-ray crystallography , it became possible to sequence protein structures. In 1959, Max Perutz determined the molecular structure of hemoglobin. For this work he shared the 1962 Nobel Prize in Chemistry with John Kendrew , who sequenced the globular protein myoglobin . The role of hemoglobin in the blood
7830-612: Was elucidated by French physiologist Claude Bernard . The name hemoglobin (or haemoglobin ) is derived from the words heme (or haem ) and globin , reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits. Hemoglobin consists of protein subunits ( globin molecules), which are polypeptides , long folded chains of specific amino acids which determine
7920-449: Was later found to reflect the activity of a special system that can recombine Lambda DNA at only one spot, normally used by the phage to insert itself into the chromosome of a host cell. Subsequently, variations of the experiment by Franklin Stahl revealed reciprocal dependencies between DNA replication and most genetic recombination. With Charles Radding, Meselson developed a model for recombination between DNA duplexes that guided research in
8010-496: Was responsible for the discovery of restriction enzymes . Since 1963 he has been interested in chemical and biological defense and arms control, has served as a consultant on this subject to various government agencies. Meselson worked with Henry Kissinger under the Nixon administration to convince President Richard Nixon to renounce biological weapons, suspend chemical weapons production, and support an international treaty prohibiting
8100-602: Was to Jeanne Guillemin , with whom he shares two stepsons. Geneticist A geneticist is a biologist or physician who studies genetics , the science of genes , heredity , and variation of organisms . A geneticist can be employed as a scientist or a lecturer . Geneticists may perform general research on genetic processes or develop genetic technologies to aid in the pharmaceutical or and agriculture industries. Some geneticists perform experiments in model organisms such as Drosophila , C. elegans , zebrafish , rodents or humans and analyze data to interpret
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