<unk>  consists of protein subunits (the globin molecules), and these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides. The amino acid sequence of any polypeptide created by a cell is in turn determined by the stretches of DNA called genes. In all proteins, it is the amino acid sequence that determines the protein's chemical properties and function. There is more than one<unk>  gene: in humans,<unk>  A (the main form of<unk>  present in adult) is coded for by the genes,<unk> A1,<unk> A2, and<unk> B. The<unk>  subunit alpha 1 and alpha 2 are coded by the genes<unk> A1 and<unk> A2, respectively, which are both on chromosome 16 and are close to each other. The<unk>  subunit beta is coded by<unk> B gene which is on chromosome 11 . The amino acid sequences of the globin proteins in<unk> s usually differ between species. These differences grow with evolutionary distance between species. For example, the most common<unk>  sequences in humans, bonobos and chimpanzees are completely identical, without even a single amino acid difference in either the alpha or the beta globin protein chains. Whereas the human and gorilla<unk>  differ in one amino acid in both alpha and beta chains, these differences grow larger between less closely related species. Even within species, variants of<unk>  exist, although one sequence is usually "most common" in each species. Mutations in the genes for the<unk>  protein in a species result in<unk>  variants. Many of these mutant forms of<unk>  cause no disease. Some of these mutant forms of<unk> , however, cause a group of hereditary diseases termed the<unk> opathies. The best known<unk> opathy is sickle-cell disease, which was the first human disease whose mechanism was understood at the molecular level. A (mostly) separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal<unk> s, through problems and mutations in globin gene regulation. All these diseases produce anemia. Protein alignment of human<unk>  proteins, alpha, beta, and delta subunits respectively. The alignments were created using 300x300px Variations in<unk>  amino acid sequences, as with other proteins, may be adaptive. For example,<unk>  has been found to adapt in different ways to high altitudes. Organisms living at high elevations experience lower partial pressures of oxygen compared to those at sea level. This presents a challenge to the organisms that inhabit such environments because<unk> , which normally binds oxygen at high partial pressures of oxygen, must be able to bind oxygen when it is present at a lower pressure. Different organisms have adapted to such a challenge. For example, recent studies have suggested genetic variants in deer mice that help explain how deer mice that live in the mountains are able to survive in the thin air that accompanies high altitudes. A researcher from the University of Nebraska-Lincoln found mutations in four different genes that can account for differences between deer mice that live in lowland prairies versus the mountains. After examining wild mice captured from both highlands and lowlands, it was found that: the genes of the two breeds are "virtually identical—except for those that govern the oxygen-carrying capacity of their<unk> ". "The genetic difference enables highland mice to make more efficient use of their oxygen", since less is available at higher altitudes, such as those in the mountains. Mammoth<unk>  featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during 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<unk>  gene of multiple species living at high elevations (Oreotrochilus, A. castelnaudii, C. violifer, P. gigas, and A. viridicuada) have caused 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 O2. These two adaptations reinforce each other and account for birds' remarkable high-altitude performance.<unk>  adaptation extends to humans, as well. There 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<unk> -oxygen affinity when compared to the mortality rate of offspring from women with low<unk> -oxygen affinity. While the exact genotype and mechanism by which this occurs 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
Lipoprotein
Ferritin
Fetal hemoglobin
Blood protein
Gamma globulin
Bile acid
Hematocrit