Ha Jiwoo, Martinson Ryan, Iwamoto Sage K, Nishi Akihiro
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90025, USA.
Evol Med Public Health. 2019 Dec 13;2019(1):232-241. doi: 10.1093/emph/eoz034. eCollection 2019.
It is known that there has been positive natural selection for hemoglobin S and C in humans despite negative health effects, due to its role in malaria resistance. However, it is not well understood, if there has been natural selection for hemoglobin E (HbE), which is a common variant in Southeast Asia. Therefore, we reviewed previous studies and discussed the potential role of natural selection in the prevalence of HbE. Our review shows that studies, evolutionary genetics studies and epidemiologic studies largely support an involvement of natural selection in the evolution of HbE and a protective role of HbE against malaria infection. However, the evidence is inconsistent, provided from different regions, and insufficient to perform an aggregated analysis such as a meta-analysis. In addition, few candidate gene, genome-wide association or epistasis studies, which have been made possible with the use of big data in the post-genomic era, have investigated HbE. The biological pathways linking HbE and malaria infection have not yet been fully elucidated. Therefore, further research is necessary before it can be concluded that there was positive natural selection for HbE due to protection against malaria. Lay summary: Our review shows that evidence largely supports an involvement of natural selection in the evolution of HbE and a protective role of HbE against malaria. However, the evidence is not consistent. Further research is necessary before it is concluded.
众所周知，尽管对健康有负面影响，但由于血红蛋白S和C在抵抗疟疾方面的作用，人类对其存在正向自然选择。然而，对于东南亚常见的血红蛋白E（HbE）变体是否存在自然选择，目前尚不清楚。因此，我们回顾了以往的研究，并讨论了自然选择在HbE流行率中的潜在作用。我们的综述表明，群体遗传学研究、进化遗传学研究和流行病学研究在很大程度上支持自然选择参与了HbE的进化以及HbE对疟疾感染的保护作用。然而，这些证据并不一致，来自不同地区，且不足以进行诸如荟萃分析之类的汇总分析。此外，在后基因组时代利用大数据得以开展的候选基因、全基因组关联或上位性研究中，很少有研究调查HbE。连接HbE与疟疾感染的生物学途径尚未完全阐明。因此，在得出由于对疟疾的保护作用而对HbE存在正向自然选择这一结论之前，有必要进行进一步研究。外行总结：我们的综述表明，证据在很大程度上支持自然选择参与了HbE的进化以及HbE对疟疾的保护作用。然而，证据并不一致。在得出结论之前，有必要进行进一步研究。
