IAP-24-025
The impact of horizontal gene transfer on the evolution of eukaryotes
Horizontal gene transfer (HGT) is defined as the movement of genetic material across extended phylogenetic distances. Because whole genes can be transferred in a single event, HGT can result in the rapid evolution of new traits in recipient organisms, and can increase the size of the available ‘gene pool’ by bringing together genetic material from lineages that may be millions of years diverged. In bacteria, HGT is now understood to be a major force shaping their evolution, and can result in the rapid evolution of traits such as drug resistance. In eukaryote species such as animals, fungi, plants and protists, however, the relative importance of HGT to evolution is controversial. Is HGT a rare event with little evolutionary consequences, or can it explain major innovations in the evolution of eukaryotes, that might be particularly important in the evolution of pathogens and parasites? Despite a growing list of well-supported specific examples of HGT in a range of eukaryote species (including insects, nematodes, rotifers; see references), there is yet to be a systematic evaluation of its rate and impact across the eukaryote tree of life. This represents a gap in our understanding of the evolutionary mechanisms that drive innovation, adaptation, and diversification of eukaryote lineages.
A previous barrier has been limitations to the quality and quantity of eukaryote genomes, as well as technical difficulties in detecting HGT from whole-genome data. Recently, however, initiatives such as the Darwin Tree of Life programme are set to generate tens of thousands of exceptionally high-quality genome sequences for a diverse range of eukaryote species. The breadth and quality of these data present a timely and exciting opportunity to better understand the contribution of this remarkable molecular mechanism to eukaryote evolution.
Research objectives
Primary objectives will centre around the following core research questions, with scope for modification or alternative directions depending on the interests of the student:
1. What is the distribution of HGT across the eukaryote tree of life, and do certain species characteristics make it more or less likely?
2. High HGT is known in some groups, such as the freshwater microinvertebrates bdelloid rotifers. Do other ‘hotspots’ of HGT exist, and if so, what might explain them?
3. To what extent has HGT contributed to the evolution of pathogens, pests and parasites as a mechanism that facilitates access to abundant genetic innovation?
4. What are the functions of ‘foreign’ genes and how does natural selection act on them once they have made the jump?
Overall, the project will formulate a new synthesis on eukaryote HGT to determine its importance in the evolution of eukaryotes, and will advance our understanding of the fundamental evolutionary forces that shape the genomes of all of life.
Methodology
The project will combine a variety of comparative genomics, bioinformatics, and quantitative and phylogenetic approaches, outlined below:
1. The student will write their own software to develop a gold-standard bioinformatics workflow for the accurate detection of HGT candidate genes, or improve and integrate existing tools for this purpose.
2. The student will then utilise the increasing number of high-quality eukaryote genomes to quantify the amount of HGT across the eukaryote tree of life. Initial analyses will focus on prokaryote-to-eukaryote HGT. Suitable data for over 3200 eukaryote species already exists in GenBank (~12% of eukaryote diversity at the family level), with 1000s planned over the next year.
3. Phylogenetic modelling methods will be used to understand the evolutionary dynamics of HGT and identify hotspots of high activity, with additional in-depth analyses on specific taxa depending on results and the student’s own interests.
4. Gene annotation methods will be used to ascribe putative functions to foreign genes, and test if certain types of genes are more likely to be transferred.
5. Finally, the student will test for phylogenetic correlations between life-history traits of recipient species and the rate of HGT to understand if certain characteristics increase the likelihood of HGT.
Project Timeline
Year 1
The PhD will begin with a literature review on eukaryote HGT and an assessment of current HGT detection tools, and training/development of key coding and software engineering skills (Python, R, git, bash).
Year 2
Year 2 will focus on software development and testing of bioinformatics workflows for HGT detection, collecting and curating genome data (available from public genome databases), and running the core analyses.
Year 3
Year 3 will focus on phylogenetic modelling of HGT evolutionary dynamics to identify hotspots, functional annotation of HGT candidate genes, and statistical modelling of correlations between HGT level and species characteristics.
Year 3.5
Thesis write-up and submission, preparation of manuscripts for publication.
Training
& Skills
The student will be embedded in the outstanding research environment of the department of Biological and Environmental Sciences (BES) at the University of Stirling. The student will be expected to fully participate in, and benefit from, ongoing research activities such as lab groups, journal clubs, and student-led research symposiums.
The successful student will acquire a broad range of both general and specific research skills.
Specific skills include proficiency in a number of scripting languages (e.g. Python, Perl, R, bash), software engineering, bioinformatics and high-performance computer science, genome assembly and annotation, comparative genomics, phylogenetics and phylogenetic statistical modelling. Opportunities for training in specific skills (e.g. coding) will be provided, depending on the student’s background.
General skills include science communication (scientific writing, paper publication and conference presentation). Training will be provided to ensure the candidate is able to publish research papers and attend conferences during the timeframe of the PhD. A broad range of additional training opportunities and transferrable skills will be available to the candidate through the University of Stirling and the IAPETUS DTP.
References & further reading
For a general review of eukaryote HGT see:
1. Husnik, F. & McCutcheon, J. P. Functional horizontal gene transfer from bacteria to eukaryotes. Nat. Rev. Microbiol. 16, 67–79 (2018). DOI: https://doi.org/10.1038/nrmicro.2017.137
2. Leger, M. M., Eme, L., Stairs, C. W. & Roger, A. J. Demystifying eukaryote lateral gene transfer. Bioessays 40, e1700242 (2018). DOI: https://doi.org/10.1002/bies.201700242
3. Cote-L’Heureux, A., Maurer-Alcalá, X. X. & Katz, L. A. Old genes in new places: A taxon-rich analysis of interdomain lateral gene transfer events. PLoS Genet. 18, e1010239 (2022). DOI: https://doi.org/10.1371/journal.pgen.1010239
For exciting specific cases of HGT in rotifers, insects and nematodes see:
4. Nowell, R. W. et al. Bdelloid rotifers deploy horizontally acquired biosynthetic genes against a fungal pathogen. Nature Communications 15, 1–17 (2024). DOI: https://doi.org/10.1038/s41467-024-49919-1
5. Li, Y. et al. HGT is widespread in insects and contributes to male courtship in lepidopterans. Cell 185, 2975–2987.e10 (2022). DOI: https://doi.org/10.1016/j.cell.2022.06.014
6. Han, Z. et al. Horizontally acquired cellulases assist the expansion of dietary range in Pristionchus nematodes. Mol. Biol. Evol. 39, (2022). DOI: https://doi.org/10.1093/molbev/msab370
