基于人群的人类线粒体遗传多样性研究通常需要将线粒体DNA(mtDNA)单倍型分类为超过5400个描述的单倍群,并进一步将这些分组为层次结构更高的单倍群。这样的次级单倍群分组(例如,“宏观单倍群”)在不同的研究中有所不同,因为它们取决于样品质量,单倍群调用的技术因素,研究的目的,以及研究人员对mtDNA单倍群命名法的理解。保留历史命名法加上越来越多的新描述的mtDNA谱系导致越来越复杂和不一致的命名法,不能很好地反映系统发育。这种“混乱”为科学出版物中的错误和不一致的分组留下了空间,特别是当单倍群名称用作辅助分组的代理时,代表了科学误解的来源。在这里,我们探讨了系统发育不敏感的次级mtDNA单倍群分组的影响,以及缺乏对下游分析和遗传数据解释的标准化二级单倍群分组。我们证明,当应用不同的次级mtDNA分组时,基于频率的分析会产生不一致的结果,因此允许对相同的遗传数据进行截然不同的解释。缺乏关于如何选择适当的二级单倍群分组的指导方针和建议,这给结果的解释带来了一个问题。以及它们在不同研究中的比较和可重复性。为了减少源自任意定义的基于次要命名法的分组的偏差,我们建议,针对mtDNA单倍群命名法使用的mtDNA系统发育的未来更新还应提供定义明确和标准化的基于系统发育有意义算法的次级单倍群分组,例如“宏单倍群”,\"中群单倍群\",和“微单倍群”。理想情况下,每个二级单倍群分组水平都应提供有关不同人群历史事件的信息.可以使用TreeCluster轻松定义单倍群分组的系统发育信息水平,然后实现为haplogroup调用者,如HaploGrep3。这将促进跨研究的可重复性,为基于人群的研究提供分组标准,并减少未来研究中与单倍群命名相关的错误。
Population-based studies of human mitochondrial genetic diversity often require the classification of mitochondrial DNA (mtDNA) haplotypes into more than 5400 described haplogroups, and further
grouping those into hierarchically higher haplogroups. Such secondary haplogroup groupings (e.g., \"macro-haplogroups\") vary across studies, as they depend on the sample quality, technical factors of haplogroup calling, the aims of the study, and the researchers\' understanding of the mtDNA haplogroup nomenclature. Retention of historical nomenclature coupled with a growing number of newly described mtDNA lineages results in increasingly complex and inconsistent nomenclature that does not reflect phylogeny well. This \"clutter\" leaves room for
grouping errors and inconsistencies across scientific publications, especially when the haplogroup names are used as a proxy for secondary groupings, and represents a source for scientific misinterpretation. Here we explore the effects of phylogenetically insensitive secondary mtDNA haplogroup groupings, and the lack of standardized secondary haplogroup groupings on downstream analyses and interpretation of genetic data. We demonstrate that frequency-based analyses produce inconsistent results when different secondary mtDNA groupings are applied, and thus allow for vastly different interpretations of the same genetic data. The lack of guidelines and recommendations on how to choose appropriate secondary haplogroup groupings presents an issue for the interpretation of results, as well as their comparison and reproducibility across studies. To reduce biases originating from arbitrarily defined secondary nomenclature-based groupings, we suggest that future updates of mtDNA phylogenies aimed for the use in mtDNA haplogroup nomenclature should also provide well-defined and standardized sets of phylogenetically meaningful algorithm-based secondary haplogroup groupings such as \"macro-haplogroups\", \"meso-haplogroups\", and \"micro-haplogroups\". Ideally, each of the secondary haplogroup
grouping levels should be informative about different human population history events. Those phylogenetically informative levels of haplogroup groupings can be easily defined using TreeCluster, and then implemented into haplogroup callers such as HaploGrep3. This would foster reproducibility across studies, provide a
grouping standard for population-based studies, and reduce errors associated with haplogroup nomenclatures in future studies.