Systematic Detection of Large-Scale Multigene Horizontal Transfer in Prokaryotes

Abstract

Horizontal gene transfer (HGT) is central to prokaryotic evolution. However, little is known about the “scale” of individual HGT events. In this work, we introduce the first computational framework to help answer the following fundamental question: How often does more than one gene get horizontally transferred in a single HGT event? Our method, called HoMer, uses phylogenetic reconciliation to infer single-gene HGT events across a given set of species/strains, employs several techniques to account for inference error and uncertainty, combines that information with gene order information from extant genomes, and uses statistical analysis to identify candidate horizontal multi-gene transfers (HMGTs) in both extant and ancestral species/strains. HoMer is highly scalable and can be easily used to infer HMGTs across hundreds of genomes. We apply HoMer to a genome-scale dataset of over 22000 gene families from 103 Aeromonas genomes and identify a large number of plausible HMGTs of various scales at both small and large phylogenetic distances. Analysis of these HMGTs reveals interesting relationships between gene function, phylogenetic distance, and frequency of multi-gene transfer. Among other insights, we find that (i) the observed relative frequency of HMGT increases as divergence between genomes increases, (ii) HMGTs often have conserved gene functions, and (iii) rare genes are frequently acquired through HMGT. We also analyze in detail HMGTs involving the zonula occludens toxin and type III secretion systems. By enabling the systematic inference of HMGTs on a large scale, HoMer will facilitate a more accurate and more complete understanding of HGT and microbial evolution.

HGTree v2.0: a comprehensive database update for horizontal gene transfer (HGT) events detected by the tree-reconciliation method

“…For the second round of the Ranger-DTL step (as mentioned above in the ‘Data collection and processing’ section), as prior research exemplified, the change in transfer costs from ‘3’ to ‘4’ resulted in the detection of more reliable HGT-related genes, but much fewer in number. Those genes also had higher risks of false negatives ( 40 , 41 ). However, by comparing transfer cost ‘4’ results with cost ‘3’ results during the aggregation step, the chances of false negatives could be reduced ( 41 ).…”

“…Those genes also had higher risks of false negatives ( 40 , 41 ). However, by comparing transfer cost ‘4’ results with cost ‘3’ results during the aggregation step, the chances of false negatives could be reduced ( 41 ). This was because the AggregateRanger step aggregated all the Ranger-DTL results (per orthology group) into one result and provided the percentage of genes in each orthology group that showed 100% consistent ‘events’ and ‘mapping’ among all optimally calculated Ranger results ( 23 ).…”

Tackling the Pangenome Dilemma Requires the Concerted Analysis of Multiple Population Genetic Processes

“…Co-occurrence of genes can be caused by vertical co-inheritance, horizontal co-transfer, co-selection, that is co-occurring selection pressures, or epistasis, that is when the fitness effect of one gene depends on the presence or absence of the other gene. Notably, the relative frequency of multi-gene transfers is higher between species compared to within species ( Kloub et al 2021 ), suggesting an important role for AGT in co-transfer. Thus, gene co-occurrences cannot be simply matched with the importance of selection, contrasting previous conclusions ( McInerney 2022 ).…”

Discrepancies between prokaryotes and eukaryotes need to be considered in soil DNA‐based studies

“…Some researchers even doubt the meaningfulness of the notion of species in prokaryotes, where genes are commonly exchanged between organisms (Doolittle and Zhaxybayeva, 2009). Indeed, bacterial and archaeal genomes possess a relatively restricted number of specific genes ('core genome'), while many functional genes related to adaptations to the environment are freely transferred horizontally through plasmid exchanges and conjugation (Paquola et al, 2018;Kloub et al, 2021) (Fig. 1).…”