On the feasibility of malaria hypothesis
Abstract In 1954, Allison proposed that hemoglobin S (HbS) gene causes protection against fatal malaria. This would explain the high HbS gene frequency observed in certain regions hyperendemic for malaria, so-called “malaria hypothesis”. This in silico study was conducted to examine the feasibility...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-56515-2 |
| _version_ | 1797266822818430976 |
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| author | Farrokh Habibzadeh |
| author_facet | Farrokh Habibzadeh |
| author_sort | Farrokh Habibzadeh |
| collection | DOAJ |
| description | Abstract In 1954, Allison proposed that hemoglobin S (HbS) gene causes protection against fatal malaria. This would explain the high HbS gene frequency observed in certain regions hyperendemic for malaria, so-called “malaria hypothesis”. This in silico study was conducted to examine the feasibility of the hypothesis under more realistic initial conditions, where a mutant gene with heterozygous advantage against malaria (e.g., HbS) was introduced in a group of Neolithic hunter-gatherers who decided to start agriculture nearby water where malaria killed a proportion of population. The tribe population size, number of children born to each woman in each generation, mortality from malaria and sickle cell disease, the protection factor provided by the gene carriers against malaria, the probability of mating between the members of the parent and offspring populations, population growth, and increased fertility in women heterozygous for HbS, were also considered. For effectively confer protection against malaria within the shortest possible period, the mutation needs to be happened in a small population. For a large population, the process would take around 100 generations (~ 2500 years) or more to provide an effective protection. Even then, the probability that the new gene could survive and propagate to future generations is about 35%. Conventional population genetics equations with differential or difference equations, give totally incorrect estimates of the gene frequency in small populations; discrete mathematics should be used, instead. After introduction of the advantageous mutation, the gene frequency increased until a steady state value. This value is far less than the gene frequency reported in certain tribes of Africa. It seems that the malaria hypothesis, per se, could not explain such a high observed gene frequency, unless HbS is associated with lower mortality from other causes too. |
| first_indexed | 2024-04-25T01:06:48Z |
| format | Article |
| id | doaj.art-1ffc540ffcc84325a6867cececcd9291 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-25T01:06:48Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1ffc540ffcc84325a6867cececcd92912024-03-10T12:11:22ZengNature PortfolioScientific Reports2045-23222024-03-0114111110.1038/s41598-024-56515-2On the feasibility of malaria hypothesisFarrokh Habibzadeh0Global Virus Network (GVN), Middle East RegionAbstract In 1954, Allison proposed that hemoglobin S (HbS) gene causes protection against fatal malaria. This would explain the high HbS gene frequency observed in certain regions hyperendemic for malaria, so-called “malaria hypothesis”. This in silico study was conducted to examine the feasibility of the hypothesis under more realistic initial conditions, where a mutant gene with heterozygous advantage against malaria (e.g., HbS) was introduced in a group of Neolithic hunter-gatherers who decided to start agriculture nearby water where malaria killed a proportion of population. The tribe population size, number of children born to each woman in each generation, mortality from malaria and sickle cell disease, the protection factor provided by the gene carriers against malaria, the probability of mating between the members of the parent and offspring populations, population growth, and increased fertility in women heterozygous for HbS, were also considered. For effectively confer protection against malaria within the shortest possible period, the mutation needs to be happened in a small population. For a large population, the process would take around 100 generations (~ 2500 years) or more to provide an effective protection. Even then, the probability that the new gene could survive and propagate to future generations is about 35%. Conventional population genetics equations with differential or difference equations, give totally incorrect estimates of the gene frequency in small populations; discrete mathematics should be used, instead. After introduction of the advantageous mutation, the gene frequency increased until a steady state value. This value is far less than the gene frequency reported in certain tribes of Africa. It seems that the malaria hypothesis, per se, could not explain such a high observed gene frequency, unless HbS is associated with lower mortality from other causes too.https://doi.org/10.1038/s41598-024-56515-2Population geneticsMalariaSickle cellBalanced polymorphismSimulation |
| spellingShingle | Farrokh Habibzadeh On the feasibility of malaria hypothesis Scientific Reports Population genetics Malaria Sickle cell Balanced polymorphism Simulation |
| title | On the feasibility of malaria hypothesis |
| title_full | On the feasibility of malaria hypothesis |
| title_fullStr | On the feasibility of malaria hypothesis |
| title_full_unstemmed | On the feasibility of malaria hypothesis |
| title_short | On the feasibility of malaria hypothesis |
| title_sort | on the feasibility of malaria hypothesis |
| topic | Population genetics Malaria Sickle cell Balanced polymorphism Simulation |
| url | https://doi.org/10.1038/s41598-024-56515-2 |
| work_keys_str_mv | AT farrokhhabibzadeh onthefeasibilityofmalariahypothesis |