Toward a unified diversity–area relationship (DAR) of species and gene diversity illustrated with the human gut metagenome

Abstract

Abstract The biogeographic diversity of the microbiome can be investigated from two perspectives: the spatiotemporal distribution of species (or any operational taxonomic unit) diversity and the spatiotemporal distribution of metagenomic gene diversity. Together, these provide a complementary understanding of taxonomic, ecological, evolutionary, and functional aspects of the microbiome. Here, we reformulate the species diversity–area relationship (DAR) to quantify and illustrate metagenomic diversity–area relationships (m‐DAR) with the gut metagenome from the human microbiome project (HMP). Using the m‐DAR, the estimated ranges of human gut metagenomic genes (MG) within and among individuals are 5.0–9.7 × 105 and 4.3–6.9 × 106, respectively; the among‐individual standard errors of these estimates (6.0–7.5 × 105) are of the same order of magnitude as the within‐individual ranges, suggesting high between‐individual variability. We similarly estimated the number of metagenome functional gene clusters (MFCG) to be 222–245 (SE = 1–2). More detailed analysis of the m‐DAR profile, pair‐wise diversity overlap (PDO), maximal accrual diversity (MAD), and ratio of individual‐ to population‐level diversity (RIP) of microbiomes of individuals with healthy guts and those with three microbiome‐associated diseases (obesity, diabetes, and inflammatory bowel disease) identified differences in m‐DAR parameters between healthy and diseased individuals. Methodologically, the m‐DAR and its associated parameters offer a unified toolset with which to study and analyze microbiomes from both species and metagenomic perspectives and to explore spatial scaling of metagenomic diversity within and among individuals. To the best of our knowledge, our illustration of m‐DAR with the human gut metagenome is the first statistically‐based estimate of the richness of human metagenomic genes at population scale.

Keywords

• diversity–area relationship
• metagenome biogeography
• metagenome diversity–area relationship
• metagenome functional gene cluster
• metagenomic gene
• species–area relationship