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Limits to Natural Selection01:38

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Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
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When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
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Updated: Dec 31, 2025

Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
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Hemoglobin E, malaria and natural selection.

Jiwoo Ha1, Ryan Martinson2, Sage K Iwamoto3

  • 1Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.

Evolution, Medicine, and Public Health
|January 1, 2020
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Natural selection may have favored hemoglobin E (HbE) due to malaria resistance, particularly in Southeast Asia. However, current evidence is inconsistent, requiring further research to confirm this evolutionary link.

Keywords:
hemoglobin Emalariamalaria hypothesisnatural selection

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Area of Science:

  • Human evolutionary genetics
  • Population genetics
  • Molecular anthropology

Background:

  • Hemoglobin S and C variants show evidence of positive natural selection due to malaria resistance.
  • Hemoglobin E (HbE) is a common variant in Southeast Asia, but its evolutionary history and selective pressures are less understood.
  • Investigating the role of natural selection in HbE prevalence is crucial for understanding human adaptation.

Purpose of the Study:

  • To review existing literature on the evolution of Hemoglobin E (HbE).
  • To discuss the potential role of natural selection in the prevalence of HbE.
  • To identify gaps in current research regarding HbE and malaria resistance.

Main Methods:

  • Comprehensive literature review of in vitro, evolutionary genetics, and epidemiologic studies.
  • Analysis of evidence for natural selection acting on HbE.
  • Assessment of the protective role of HbE against malaria.

Main Results:

  • Existing studies largely support natural selection's involvement in HbE evolution and a protective effect against malaria.
  • Evidence is inconsistent across different geographic regions.
  • Current data is insufficient for meta-analysis, and few large-scale genomic studies have investigated HbE.
  • The precise biological mechanisms linking HbE to malaria protection remain unclear.

Conclusions:

  • While evidence suggests natural selection may have favored HbE for malaria resistance, the findings are not conclusive.
  • Inconsistent data and limited large-scale genomic research necessitate further investigation.
  • More research is required to definitively establish positive natural selection for HbE due to malaria protection.