Question

Horizontal Gene Transfer is important for prokaryotes. What would happen if there was no HGT: In the human gut?

Answer 1

Horizontal gene transfer is the lateral exchange of genes between unicellular and/or multicellular organisms. In contrast to the vertical gene transfer, i.e., between generations, HGT enables the transfer of genetic sequences between remote species-mediated usually by transformation, transduction, and conjugal transfer or with specific gene transfer agents .

Horizontal gene transfer has been demonstrated for almost all phylogenetic groups in all three domains of life as a crucial factor in the evolution of various organisms (7–9), including plants (10, 11), viruses (12), archaea (13), fungi (14, 15), and animals (16). While the evolution of the Eukaryotes is largely driven by vertical inheritance, the predominant form of evolution among the bacteria and archaea is HGT, the rate of which is comparable to the point mutation’s rate, surpassing the gene duplication rate (17). Thus, for these two domains, HGT is an essential way for genome diversification and novel function procurement to survive under the pressure of natural selection and to reproduce. Therefore, HGT is a main driver of microbial evolution and ecology. Bacteria have developed multiple natural genetic tools to exchange genetic material between strains, species, genera, and even higher taxa. While the phenomenon of HGT can be encountered in virtually any ecosystem, the focus of the present review is HGT in the human gut. This is complemented by a potential contribution to changing dietary and lifestyle habits to HGT.

Since the gut is a niche mainly colonized by a plethora of microbial species, it is logical to presume that the genomes of methanogenic archaea in the intestine have acquired their ability to survive and proliferate in this environment through interdomain HGT from the microbial counterpart that dominate this niche. Recently, contribution of HGT to the gene repertoire in a gut-adapted commensal methanogen Methanobrevibacter smithii, which is the richest archaeon in the human gross intestine, has been evaluated (26). A phylogenetic tree-based genome-wide survey of putative genes, presumably acquired as a result of HGT, established that over 15% of the coding sequences in M. smithii could be inferred as of bacterial origin. Laterally acquired genes largely contribute to surface functions and encode glycosyltransferases and adhesin-like proteins, which also can act as virulence factors in pathogens. In addition, several important ABC transporters, especially metal transporters are potentially of microbial origin. Metals such as zinc, for example, are important for bacterial growth, and there is a strong competition for it among intestinal microbiota as well (27). Thus, the microbial genes acquired by this archaeon contributed to the host adaptation by permitting an extended variety of surface structures and enhancing the efficiency of metal ion uptake in the competitive gut niche. Taken together, adaptation of M. smithii to the niche involved the acquisition of bacterial genes into its genome to adjust its lifestyle.

A comparative study of fecal samples from mono and dizygotic twins revealed that the pan-genome of M. smithii “contains 987 genes conserved in all strains, and 1,860 variably represented genes” (28). Strains from monozygotic and dizygotic twins had a comparable degree of shared genes and SNPs and were significantly more similar than strains isolated from mothers or members of their families. The 101 adhesin-like proteins in the pan-genome (45 ± 6 per strain) exhibited strain-specific differences in expression and responsiveness to format. The authors hypothesized that M. smithii strains use their different repertoires of adhesin-like proteins to create diversity in their metabolic niches, by permitting them to create syntrophic relationships with bacterial partners with differential metabolic capacities and patterns of co-occurrence. It is generally accepted that the core genome genes are less prone to HGT than that of the auxiliary genome. Thus, the majority of genes in the pan-genome of M. smithii are laterally circulating among the strains of this species.

More information on the magnitude of HGT operating in the human intestine came from the study of Zaneveld et al. (29). They revealed that enteric-adapted genomes are more comparable in gene content at a given evolutionary distance than non-gut genomes. Thus, common functional needs or magnified HGT causes similarities in genes within the gut compartment. Notably, niche specialization at short phylogenetic distances is also important in the mammalian intestine. More recently, a hypothesis that the animal gut is a melting pot for HGT has been summarized in two mini-reviews that surveyed HGT events in the mammalian gut and the role of HGT in the long-term adaptation of microbes to the intestinal milieu (30, 31). The authors concluded that the mammalian intestine is “a melting pot of genetic exchange, resulting in the large extent of HGT occurrence” (30).

Most of our knowledge of HGT has been obtained from the in vitro studies. Where the features are substantially different, especially in the gut, due to extremely dense and diverse microbiota. The plethora of functions include the suppression of settlement by pathobionts, degradation of dietary and in situ-produced components, production of nutritional factors, modulating and maintaining a functional mucosal immunity, supporting inter epithelial tight junction integrity, and contribution to intestinal epithelial homeostasis. Recently, evidence of increased DNA exchange among the Bacteroidales species within the human intestine has been reported (32). Genes that are extensively exchanged among these species encode proteins involved in fitness and multiple cycles-like alterations of gene expression. Fimbriae components may enhance attachment, utilization of new substrates increase the nutritional base, and secretion of antimicrobial molecules may confer a competitive advantage within the ecological niche. The genetic content of the “transferome” suggests that the gene transfer from the successfully adapted members of an ecosystem confers useful properties to the recipients, increasing their fitness and conferring them a competitive edge within the gut microbial ecosystem.