Horizontal Gene Transfer: From Evolutionary Flexibility to Disease Progression

Abstract

Flexibility in the exchange of genetic material takes place between different organisms of the same or different species. This phenomenon is known to play a key role in the genetic, physiological, and ecological performance of the host. Exchange of genetic materials can cause both beneficial and/or adverse biological consequences. Horizontal gene transfer (HGT) or lateral gene transfer (LGT) as a general mechanism leads to biodiversity and biological innovations in nature. HGT mediators are one of the genetic engineering tools used for selective introduction of desired changes in the genome for gene/cell therapy purposes. HGT, however, is crucial in development, emergence, and recurrence of various human-related diseases, such as cancer, genetic-, metabolic-, and neurodegenerative disorders and can negatively affect the therapeutic outcome by promoting resistant forms or disrupting the performance of genome editing toolkits. Because of the importance of HGT and its vital physio- and pathological roles, here the variety of HGT mechanisms are reviewed, ranging from extracellular vesicles (EVs) and nanotubes in prokaryotes to cell-free DNA and apoptotic bodies in eukaryotes. Next, we argue that HGT plays a role both in the development of useful features and in pathological states associated with emerging and recurrent forms of the disease. A better understanding of the different HGT mediators and their genome-altering effects/potentials may pave the way for the development of more effective therapeutic and diagnostic regimes.

Keywords: antibiotic resistance; apoptotic bodies; cancer; cell-free DNA; evolution; exosomes; horizontal gene transfer; transposable elements.

FIGURE 1

Variety of HGT mediators in prokaryotes. Data obtained from Ficht (2011), Lang et al. (2012), Borgeaud et al. (2015), Hall et al. (2017), Tzipilevich et al. (2017).

FIGURE 2

Causes and consequences of prokaryote-prokaryote HGT. Mediators are shown in white boxes and consequences are shown in colored boxes. As a natural defense mechanism in some bacteria, the CRISPR-Cas9 system can overcome horizontal transfer of genetic material, mediated by EVs and/or plasmids. HGT consequence in all cases is the emergence of resistant bacteria strains and the spread of human-related infections. Data obtained from Klieve et al. (2005), Babić et al. (2008), Husnik et al. (2013), Marraffini and Sontheimer (2008), Dubey and Ben-Yehuda (2011), Borgeaud et al. (2015), Cooper et al. (2017), Tzipilevich et al. (2017), Price et al. (2019).

FIGURE 3

Causes and consequences of HGT in eukaryotes. Mediators (causes) are shown in blue boxes. Data obtained from de la Taille et al. (1999), Holmgren et al. (1999), Bergsmedh et al. (2001), Fronzes et al. (2009), Trejo-Becerril et al. (2012), Berridge et al. (2015), Hancks and Kazazian (2016), Lacroix and Citovsky (2016), Nishida-Aoki et al. (2017), Robinson et al. (2017), Gao et al. (2018), Jang et al. (2019), Kawamura et al. (2019), Ono et al. (2019), Schumann et al. (2019).