in what type of environment is being heterozygous in regards to the sickle cell trait an advantage?

Example in which having two unlike versions of a gene provides an advantage

A heterozygote advantage describes the example in which the heterozygous genotype has a higher relative fitness than either the homozygous dominant or homozygous recessive genotype. The specific example of heterozygote advantage due to a single locus is known as overdominance.^{[i] [2]} Overdominance is a condition in genetics where the phenotype of the heterozygote lies exterior of the phenotypical range of both homozygote parents, and heterozygous individuals have a higher fettle than homozygous individuals.

Polymorphism can be maintained past selection favoring the heterozygote, and this mechanism is used to explain the occurrence of some kinds of genetic variability. A common example is the case where the heterozygote conveys both advantages and disadvantages, while both homozygotes convey a disadvantage. A well-established instance of heterozygote advantage is that of the gene involved in sickle cell anaemia.

Often, the advantages and disadvantages conveyed are rather complicated, because more than ane gene may influence a given trait or morph. Major genes almost always take multiple furnishings (pleiotropism), which can simultaneously convey separate advantageous traits and disadvantageous traits upon the aforementioned organism. In this instance, the state of the organism's environment will provide selection, with a net effect either favoring or working in opposition to the gene, until an environmentally adamant equilibrium is reached.

Heterozygote advantage is a major underlying mechanism for heterosis, or "hybrid vigor", which is the improved or increased function of any biological quality in a hybrid offspring. Previous research, comparison measures of say-so, overdominance and epistasis (mostly in plants), found that the majority of cases of heterozygote advantage were due to complementation (or dominance), the masking of deleterious recessive alleles past wild-blazon alleles, as discussed in the articles Heterosis and Complementation (genetics), only in that location were as well findings of overdominance, especially in rice.^[ii] More recent enquiry, however, has established that there is likewise an epigenetic contribution to heterozygote reward, primarily equally determined in plants,^{[3] [4]} though likewise reported in mice.^[five]

In theory [edit]

When 2 populations of any sexual organism are separated and kept isolated from each other, the frequencies of deleterious mutations in the two populations will differ over time, by genetic drift. It is highly unlikely, however, that the same deleterious mutations will be common in both populations later a long menstruum of separation. Since loss-of-function mutations tend to exist recessive (given that dominant mutations of this type generally forestall the organism from reproducing and thereby passing the gene on to the next generation), the outcome of whatsoever cantankerous between the two populations volition be fitter than the parent.

This article deals with the specific case of fitness overdominance, where the fitness advantage of the cross is caused past beingness heterozygous at 1 specific locus alone.

Experimental confirmation [edit]

Cases of heterozygote advantage have been demonstrated in several organisms, including humans. The first experimental confirmation of heterozygote reward was with Drosophila melanogaster, a fruit fly that has been a model organism for genetic inquiry. In a classic study on the ebony mutation, Kalmus demonstrated how polymorphism can persist in a population through heterozygote advantage.^[vi]

If weakness were the but event of the mutant allele, so it conveyed simply disadvantages, natural choice would weed out this version of the gene until it became extinct from the population. However, the aforementioned mutation also conveyed advantages, providing improved viability for heterozygous individuals. The heterozygote expressed none of the disadvantages of homozygotes, yet gained improved viability. The homozygote wild type was perfectly healthy, simply did not possess the improved viability of the heterozygote, and was thus at a disadvantage compared to the heterozygote in survival and reproduction.

This mutation, which at first glance appeared to be harmful, conferred plenty of an advantage to heterozygotes to go far benign, and so that it remained at dynamic equilibrium in the gene pool. Kalmus introduced flies with the ebony mutation to a wild-type population. The ebony allele persisted through many generations of flies in the written report, at genotype frequencies that varied from 8% to 30%. In experimental populations, the ebony allele was more than prevalent and therefore advantageous when flies were raised at low, dry out temperatures, but less so in warm, moist environments.

In human genetics [edit]

Sickle-cell anemia [edit]

Sickle-cell anemia (SCA) is a genetic disorder caused by the presence of two incompletely recessive alleles. When a sufferer's carmine blood cells are exposed to low-oxygen conditions, the cells lose their healthy round shape and become sickle-shaped. This deformation of the cells tin can cause them to become lodged in capillaries, depriving other parts of the body of sufficient oxygen. When untreated, a person with SCA may suffer from painful periodic bouts, frequently causing damage to internal organs, strokes, or anemia. Typically, the disease results in premature death.

Possible reward of being heterozygous for sickle cell anemia disease (A) vs. normal blood jail cell response (B) when infected with malaria.

Because the genetic disorder is incompletely recessive, a person with merely ane SCA allele and ane unaffected allele volition accept a "mixed" phenotype: The sufferer will non experience the ill effects of the disease, yet will still possess a sickle cell trait, whereby some of the ruby blood cells undergo benign effects of SCA, simply nada severe enough to be harmful. Those affected with sickle-prison cell trait are also known as carriers: If two carriers have a kid, there is a 25% chance their child will take SCA, a 50% chance their child will be a carrier, and a 25% adventure that the child will neither have SCA nor be a carrier. Were the presence of the SCA allele to confer only negative traits, its allele frequency would be expected to decrease generation later on generation, until its presence were completely eliminated past selection and by chance.

Nevertheless, convincing evidence indicates, in areas with persistent malaria outbreaks, individuals with the heterozygous land take a distinct advantage (and this is why individuals with heterozygous alleles are far more common in these areas).^{[vii] [8]} Those with the benign sickle trait possess a resistance to malarial infection. The pathogen that causes the illness spends part of its bike in the red blood cells and triggers an abnormal drop in oxygen levels in the prison cell. In carriers, this drop is sufficient to trigger the total sickle-cell reaction, which leads to infected cells being rapidly removed from circulation and strongly limiting the infection's progress. These individuals have a slap-up resistance to infection and take a greater chance of surviving outbreaks. All the same, those with two alleles for SCA may survive malaria, but volition typically die from their genetic disease unless they accept admission to advanced medical care. Those of the homozygous "normal" or wild-type case will have a greater take a chance of passing on their genes successfully, in that in that location is no chance of their offspring's suffering from SCA; yet, they are more susceptible to dying from malarial infection before they take a chance to laissez passer on their genes.

This resistance to infection is the main reason the SCA allele and SCA disease still exist. It is institute in greatest frequency in populations where malaria was and often yet is a serious trouble. Approximately one in 10 African Americans is a carrier,^[9] as their recent beginnings is from malaria-stricken regions. Other populations in Africa, Bharat, the Mediterranean and the Heart Eastward have college allele frequencies, besides. Every bit effective antimalarial treatment becomes increasingly available to malaria-stricken populations, the allele frequency for SCA is expected to decrease, so long as SCA treatments are unavailable or only partially constructive. If effective sickle-cell anemia treatments become available to the aforementioned degree, allele frequencies should remain at their nowadays levels in these populations. In this context, 'treatment effectiveness' refers to the reproductive fitness it grants, rather than the degree of suffering alleviation.

Cystic fibrosis [edit]

Cystic fibrosis (CF) is an autosomal recessive hereditary monogenic disease of the lungs, sweat glands and digestive system. The disorder is caused by the malfunction of the CFTR poly peptide, which controls intermembrane transport of chloride ions, which is vital to maintaining equilibrium of water in the trunk. The malfunctioning protein causes sticky mucus to form in the lungs and intestinal tract. Before modernistic times, children born with CF would take a life expectancy of simply a few years, just modern medicine has made it possible for these people to alive into adulthood. However, fifty-fifty in these individuals, CF typically causes male person infertility. Information technology is the almost common genetic disease among people of European descent.

The presence of a single CF mutation may influence survival of people afflicted by diseases involving loss of body fluid, typically due to diarrhea. The almost common of these maladies is cholera, which only began killing Europeans millennia after the CF mutation frequency was already established in the population. Some other such disease that CF may protect against is typhoid.^[10] Those with cholera would oft die of dehydration due to intestinal water losses. A mouse model of CF was used to study resistance to cholera, and the results were published in Science in 1994 (Gabriel, et al.). The heterozygote (carrier) mouse had less secretory diarrhea than normal, noncarrier mice. Thus, it appeared for a fourth dimension that resistance to cholera explained the selective advantage to beingness a carrier for CF and why the carrier state was so frequent.

This theory has been chosen into question. Hogenauer, et al.^[eleven] have challenged this popular theory with a human study. Prior data were based solely on mouse experiments. These authors found the heterozygote state was indistinguishable from the noncarrier state.

Another theory for the prevalence of the CF mutation is that it provides resistance to tuberculosis. Tuberculosis was responsible for 20% of all European deaths between 1600 and 1900, so even partial protection against the illness could account for the current factor frequency.^[12]

The nearly recent hypothesis, published in the Journal of Theoretical Biology, proposed having a single CF mutation granted respiratory reward for early Europeans migrating north into the dusty wasteland left by the Last Glacial Maximum.^[13]

As of 2016, the selective pressure level for the high gene prevalence of CF mutations is still uncertain, and may exist due to an unbiased genetic drift rather than a selective advantage. Approximately one in 25 persons of European descent is a carrier of the disease, and ane in 2500 to 3000 children built-in is affected by Cystic fibrosis.

Triosephosphate isomerase [edit]

Triosephosphate isomerase (TPI) is a cardinal enzyme of glycolysis, the chief pathway for cells to obtain energy by metabolizing sugars. In humans, sure mutations within this enzyme, which impact the dimerisation of this protein, are causal for a rare illness, triosephosphate isomerase deficiency. Other mutations, which inactivate the enzyme (= null alleles) are lethal when inherited homozygously (two defective copies of the TPI gene), just have no obvious effect in heterozygotes (i defective and i normal copy). All the same, the frequency of heterozygous null alleles is much higher than expected, indicating a heterozygous advantage for TPI null alleles. The reason is unknown; however, new scientific results are suggesting cells having reduced TPI activity are more resistant against oxidative stress. PlosOne, Dec. 2006

Resistance to hepatitis C virus infection [edit]

There is evidence that genetic heterozygosity in humans provides increased resistance to certain viral infections. A significantly lower proportion of HLA-DRB1 heterozygosity exists amongst HCV-infected cases than uninfected cases. The differences were more pronounced with alleles represented as functional supertypes (P = 1.05 × x⁻⁶) than those represented as low-resolution genotypes (P = 1.99 × ten⁻³). These findings plant evidence that heterozygosity provides an advantage among carriers of different supertype HLA-DRB1 alleles against HCV infection progression to end-stage liver disease in a large-scale, long-term study population.^[xiv]

MHC heterozygosity and human odor preferences [edit]

Multiple studies have shown, in double-blind experiments, females prefer the odor of males who are heterozygous at all 3 MHC loci.^{[fifteen] [16]} The reasons proposed for these findings are speculative; however, information technology has been argued that heterozygosity at MHC loci results in more alleles to fight against a wider variety of diseases, possibly increasing survival rates against a wider range of infectious diseases.^[17] The latter claim has been tested in an experiment, which showed outbreeding mice to exhibit MHC heterozygosity enhanced their health and survival rates against multiple-strain infections.^[18]

BAFF and autoimmune disease [edit]

B-prison cell activating factor (BAFF) is a cytokine encoded by the TNFSF13B gene. A variant of the gene containing a deletion (GCTGT—>A) renders a shorter mRNA transcript that escapes degradation by microRNA, thus increasing expression of BAFF, which consequently up-regulates the humoral immune response. This variant is associated with systemic lupus erythematosus and multiple sclerosis, only heterozygote carriers of the variant have decreased susceptibility to malaria infection.^[xix]

Encounter as well [edit]

• Balanced polymorphism
• Hybrid vigour
• Miscegenation
• Overdominance
• Polymorphism (biology)

Notes [edit]

1. ^ Charlesworth D, Willis JH (November 2009). "The genetics of inbreeding low". Nat. Rev. Genet. 10 (11): 783–96. doi:10.1038/nrg2664. PMID 19834483. S2CID 771357.
2. ^ ^{a b} Carr DE, Dudash MR (June 2003). "Recent approaches into the genetic ground of inbreeding depression in plants". Philos. Trans. R. Soc. Lond. B Biol. Sci. 358 (1434): 1071–84. doi:ten.1098/rstb.2003.1295. PMC1693197. PMID 12831473.
3. ^ Chen ZJ (February 2010). "Molecular mechanisms of polyploidy and hybrid vigor". Trends Plant Sci. xv (2): 57–71. doi:10.1016/j.tplants.2009.12.003. PMC2821985. PMID 20080432.
4. ^ Baranwal VK, Mikkilineni Five, Zehr UB, Tyagi AK, Kapoor South (November 2012). "Heterosis: emerging ideas about hybrid vigour". J. Exp. Bot. 63 (18): 6309–14. doi:10.1093/jxb/ers291. PMID 23095992.
5. ^ Han Z, Mtango NR, Patel BG, Sapienza C, Latham KE (October 2008). "Hybrid vigor and transgenerational epigenetic effects on early mouse embryo phenotype". Biol. Reprod. 79 (iv): 638–48. doi:ten.1095/biolreprod.108.069096. PMC2844494. PMID 18562704.
6. ^ Kalmus, H. (1945). "Adaptive and selective responses of a population of Drosophila melanogaster containing e and e+ to differences in temperature, humidity, and to choice for evolution speed". Journal of Genetics. 47: 58–63. doi:10.1007/BF02989038. S2CID 27175926.
7. ^ Bridges, Kenneth (ii April 2002). "Malaria and the Sickle Hemoglobin Gene". Information Center for Sickle Prison cell and Thalassemic Disorders. Archived from the original on 27 November 2011.
8. ^ Bunn, H. Franklin (November one, 2012). "The triumph of good over evil: protection past the sickle jail cell cistron against malaria". Blood. ten (1182): 20–24.
9. ^ Lazarin M. A.; Haque I. Southward.; Nazareth S.; Iori Thousand.; Patterson A. S.; Jacobson J. L.; Marshall J. R.; Seltzer W. K.; Patrizio P.; Evans E. A.; Srinivasan B. S. (2013). "An empirical gauge of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals". Genet. Med. xv (iii): 178–186. doi:10.1038/gim.2012.114. PMC3908551. PMID 22975760.
10. ^ Josefson, Deborah (May 16, 1998). "CF Gene May Protect confronting Typhoid Fever". British Medical Journal. 316 (7143): 1481. doi:10.1136/bmj.316.7143.1477j. PMID 9616022. S2CID 27062771.
11. ^ Högenauer C, Santa Ana CA, Porter JL, et al. (December 2000). "Agile intestinal chloride secretion in human being carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes take subnormal active intestinal chloride secretion". Am. J. Hum. Genet. 67 (6): 1422–7. doi:10.1086/316911. PMC1287919. PMID 11055897.
12. ^ MacKenzie, Debora (2006-09-07). "Cystic fibrosis gene protects confronting tuberculosis". New Scientist.
13. ^ Borzan V, Tomašević B, Kurbel S (2014). "Hypothesis: Possible respiratory advantages for heterozygote carriers of cystic fibrosis linked mutations during dusty climate of last glaciation". J Theor Biol. 363: 164–168. Bibcode:2014JThBi.363..164B. doi:10.1016/j.jtbi.2014.08.015. PMID 25150458.
14. ^ Hraber P, Kuiken C, Yusim Grand (December 2007). "Evidence for human leukocyte antigen heterozygote advantage confronting hepatitis C virus infection". Hepatology. 46 (6): 1713–21. doi:x.1002/hep.21889. PMID 17935228.
15. ^ Rikowski A, Grammer Yard (May 1999). "Man trunk odour, symmetry and attractiveness". Proc. Biol. Sci. 266 (1422): 869–74. doi:x.1098/rspb.1999.0717. PMC1689917. PMID 10380676.
16. ^ Thornhill R, Gangestad S, Miller R, Scheyd M, McCollough J, Franklin M (March–April 2013). "Major histocompatibility complex genes, symmetry, and torso olfactory property attractiveness in men and women". Behavioral Environmental. xiv (5): 668–678. doi:x.1093/beheco/arg043.
17. ^ Buss, David M. (2005). The Handbook of Evolutionary Psychology. John Wiley & Sons. p. 357. ISBN978-0-471-72722-iv.
18. ^ Penn DJ, Damjanovich K, Potts WK (Baronial 2002). "MHC heterozygosity confers a selective reward against multiple-strain infections". Proc. Natl. Acad. Sci. U.Southward.A. 376 (17): 11260–four. Bibcode:2002PNAS...9911260P. doi:10.1073/pnas.162006499. PMC123244. PMID 12177415.
19. ^ Steri M, et al. (Apr 2017). "Overexpression of the Cytokine BAFF and Autoimmunity Risk". New England Journal of Medicine. 46 (17): 1615–26. doi:10.1056/NEJMoa1610528. PMC5605835. PMID 28445677.

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Source: https://en.wikipedia.org/wiki/Heterozygote_advantage

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