Lateral Gene Transfer Dynamics in the Ancient Bacterial Genus Streptomyces

Abstract

Lateral gene transfer (LGT) profoundly shapes the evolution of bacterial lineages. LGT across disparate phylogenetic groups and genome content diversity between related organisms suggest a model of bacterial evolution that views LGT as rampant and promiscuous. It has even driven the argument that species concepts and tree-based phylogenetics cannot be applied to bacteria. Here, we show that acquisition and retention of genes through LGT are surprisingly rare in the ubiquitous and biomedically important bacterial genus Streptomyces Using a molecular clock, we estimate that the Streptomyces bacteria are ~380 million years old, indicating that this bacterial genus is as ancient as land vertebrates. Calibrating LGT rate to this geologic time span, we find that on average only 10 genes per million years were acquired and subsequently maintained. Over that same time span, Streptomyces accumulated thousands of point mutations. By explicitly incorporating evolutionary timescale into our analyses, we provide a dramatically different view on the dynamics of LGT and its impact on bacterial evolution.IMPORTANCE Tree-based phylogenetics and the use of species as units of diversity lie at the foundation of modern biology. In bacteria, these pillars of evolutionary theory have been called into question due to the observation of thousands of lateral gene transfer (LGT) events within and between lineages. Here, we show that acquisition and retention of genes through LGT are exceedingly rare in the bacterial genus Streptomyces, with merely one gene acquired in Streptomyces lineages every 100,000 years. These findings stand in contrast to the current assumption of rampant genetic exchange, which has become the dominant hypothesis used to explain bacterial diversity. Our results support a more nuanced understanding of genetic exchange, with LGT impacting evolution over short timescales but playing a significant role over long timescales. Deeper understanding of LGT provides new insight into the evolutionary history of life on Earth, as the vast majority of this history is microbial.

Keywords: antibiotics; evolutionary genomics; horizontal gene transfer; molecular clock; species concepts.

FIG 1

Genome-based phylogeny and molecular clock for the genus Streptomyces. TIGRFAM-based multilocus phylogeny of Streptomyces using 94 universally conserved housekeeping genes. Branch lengths indicate Reltime-estimated divergence times. Bootstrap values are shown by colored circles on all nodes with values of ≤95. Streptomyces and Kitasatospora are abbreviated as Strept and Kit, respectively.

FIG 2

Streptomyces genome content conservation and divergence. (A) Proteinortho gene families present, conserved, and enriched in three groups of Streptomyces (clade I, clade II, and other lineages; based on Fig. 1). Gene family enrichment within subsets of Streptomyces was determined using Fisher’s exact test. (B) Pairwise comparison of conserved Proteinortho gene family percentage and TIGRFAM core gene sequence percent identity.

FIG 3

Rate of lateral gene transfer in Streptomyces. (A) Average rate of LGT across the Streptomyces phylogeny. Line thickness indicates the average number of detected LGT events per genome (including ancestral reconstructions) per million years from each source. Rates greater than 3 are labeled, and all rates appear in Table S2 in the supplemental material. (B) Detected rate of LGT on each branch of the phylogeny. Detected LGT rate is negatively correlated with branch length.

FIG 4

Rate of point mutations in TIGRFAM gene families. Bact-core genes consist of 94 housekeeping TIGRFAM gene families conserved across bacteria. Strept-conserved genes consist of 705 TIGRFAM gene families that are found in 95% of our Streptomyces genome data set. (A) The observed rate of synonymous point mutations varies by gene data set and pairwise distance. (B) The observed rate of nonsynonymous sites also varies by data set and pairwise distance, but to a lesser degree than that of synonymous sites.

FIG 5

Sources of laterally transferred secondary metabolite biosynthesis genes. (A) Most biosynthetic gene clusters have acquired some genes through LGT within the last 50 my. (B) The vast majority of clusters appear to be a mix of genes from multiple sources, including being retained over millions of years within a lineage through vertical inheritance.