Phylogenetics and the Human Microbiome

—The human microbiome is the ensemble of genes in the microbes that live inside and on the surface of humans. Because microbial sequencing information is now much easier to come by than phenotypic information, there has been an explosion of sequencing and genetic analysis of microbiome samples. Much of the analytical work for these sequences involves phylogenetics, at least indirectly, but methodology has developed in a somewhat different direction than for other applications of phylogenetics. In this article, I review the field and its methods from the perspective of a phylogeneticist, as well as describing current challenges for phylogenetics coming from this type of work. [human microbiome; human microbiota; metagenome; microbial ecology; phylogenetic methods; 16S] The parameter regime and focus of human-associated microbial research sits outside of the traditional setting for phylogenetics methods development and application; why should our community be interested in what microbial ecologists and medical researchers have done? The answer is simple: this system is dataand question-rich. Microbes are now primarily identified by their molecular sequences because such molecular identification is much more straightforward to do in high throughput than morphological or phenotypic characterization. Indeed, microbial ecology has recently become for the most part the study of the relative abundances of various sequences derived from the environment, even if the framework for understanding between-microbe relationships includes metabolic information and other information not derived directly from sampled molecular sequences. Although there is something of a divide between phylogeny as practiced as part of microbial ecology on one hand and that for multicellular organisms on the other, there are many parallels between the two enterprises. Both communities struggle with issues of sequence alignment, large-scale tree reconstruction, and species delimitation. However, approaches differ between the microbial ecology community and that of eukaryotic phylogenetics, in part because the scope of the former contains an almost unlimited diversity of organisms, leading to additional problems above the usual. The species concept is even more problematic for microbes than for multicellular organisms, and hence there is also considerable discussion concerning how to group them into species-like units. Organizing microbes into a sensible taxonomy is a serious challenge, especially in the absence of obvious morphological features. Because of this high level of diversity and challenges with species definitions, microbial ecology researchers have developed their own explicitly phylogenetic techniques for comparing samples rather than comparing on the level of species abundances. Although there is some overlap with previous literature, these techniques could be used in a wider setting and may deserve broader consideration by the phylogenetics community. The human-associated microbial assemblage is specifically interesting because questions of microbial genomics, translated into questions of function, have important consequences for humanhealth.Additionally, due to more than a century of hospital laboratory work, our knowledge about human-associated microbes is relatively rich. This collection of microbes living inside and on our surfaces is called the human microbiota, and the ensemble of genetic information in those microbes is called the human microbiome, although usage of these terms varies (Boon et al. 2013). In this review, I will describe phylogenetics-related research happening in microbial ecology and contrast approaches between microbial researchers and what I think of as the typical Systematic Biology audience. Despite an obvious oversimplification, I will use eukaryotic phylogenetics to indicate what I think of as the mainstream of SB readership, andmicrobial phylogenetics to denote the other. I realize that there is substantial overlap—for instance the microbial community is very interested in unicellular fungi, and additionally many in the SB community do work on microbes—but this terminology will be useful for concreteness. There is of course also substantial overlap in methodology; however, as we will see there are significant differences inapproachand the twoareashavedevelopedsomewhat in parallel. I will first briefly review the recent literature on the human microbiota, then describe novel ways in which human microbiome researchers have used trees. I will finish with opportunities for the Systematic Biology audience to contribute to this field. I have made an explicit effort to make a neutral comparison between two directions rather than criticize the approximatemethods common inmicrobial phylogenetics; indeed, microbial phylogenetics requires algorithms and ideas that work in parameter regimes an order of magnitude larger than typical for eukaryotic phylogenetics. 1 Systematic Biology Advance Access published September 24, 2014 by Frerick M asen on Sptem er 5, 2014 http://sysbfordjournals.org/ D ow nladed from