Diversification of Secondary Metabolite Biosynthetic Gene Clusters Coincides with Lineage Divergence in Streptomyces.

Mallory J Choudoir,Charles Pepe-Ranney,Daniel H Buckley

doi:10.3390/antibiotics7010012

Mallory J Choudoir, Charles Pepe-Ranney + Show 1 more

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https://doi.org/10.3390/antibiotics7010012

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Journal: Antibiotics	Publication Date: Feb 13, 2018
Citations: 37	License type: CC BY 4.0

Affiliation: Cornell University

Abstract

We have identified Streptomyces sister-taxa which share a recent common ancestor and nearly identical small subunit (SSU) rRNA gene sequences, but inhabit distinct geographic ranges demarcated by latitude and have sufficient genomic divergence to represent distinct species. Here, we explore the evolutionary dynamics of secondary metabolite biosynthetic gene clusters (SMGCs) following lineage divergence of these sister-taxa. These sister-taxa strains contained 310 distinct SMGCs belonging to 22 different gene cluster classes. While there was broad conservation of these 22 gene cluster classes among the genomes analyzed, each individual genome harbored a different number of gene clusters within each class. A total of nine SMGCs were conserved across nearly all strains, but the majority (57%) of SMGCs were strain-specific. We show that while each individual genome has a unique combination of SMGCs, this diversity displays lineage-level modularity. Overall, the northern-derived (NDR) clade had more SMGCs than the southern-derived (SDR) clade (40.7 ± 3.9 and 33.8 ± 3.9, mean and S.D., respectively). This difference in SMGC content corresponded with differences in the number of predicted open reading frames (ORFs) per genome (7775 ± 196 and 7093 ± 205, mean and S.D., respectively) such that the ratio of SMGC:ORF did not differ between sister-taxa genomes. We show that changes in SMGC diversity between the sister-taxa were driven primarily by gene acquisition and deletion events, and these changes were associated with an overall change in genome size which accompanied lineage divergence.

Highlights

Microbial secondary metabolism encapsulates a remarkable diversity of natural products with an extensive range of biological activities
We show that changes in secondary metabolite biosynthetic gene clusters (SMGCs) diversity between the sister-taxa were driven primarily by gene acquisition and deletion events, and these changes were associated with an overall change in genome size which accompanied lineage divergence
We observe that SMGCs that have been inherited from a shared ancestor can vary considerably in gene content, both due to the acquisition and deletion of individual genes within each gene cluster

Summary

Introduction

Microbial secondary metabolism encapsulates a remarkable diversity of natural products with an extensive range of biological activities. While primary metabolic pathways are often conserved deeply within a phylogeny, secondary metabolic pathways are more divergent, often being species or strain-specific, with conservation sometimes observed among closely related species and genera [2]. This phylogenetic pattern suggests an adaptive role for secondary metabolites, and if secondary metabolism pathways provide adaptive benefits, their evolution might drive or reinforce evolutionary processes that result in microbial diversification and speciation [3]. The discovery and application of antibiotics revolutionized medicine in the 1940’s, sparking the “golden age” of antibiotics between 1950 and 1960, during

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