Lateral gene transfer in eukaryotes - where's the evidence?

Lateral gene transfer (LGT), or horizontal gene transfer (HGT), is widespread in bacteria. It leads to the creation of pangenomes for many bacterial species where different subpopulations contain different subsets of genes that have been incorporated from other species. It also leads to confusing phylogenetic trees such that the history of bacterial evolution looks more like a web of life than a tree [The Web of Life].

Bacterial-like genes are also found in eukaryotes. Many of them are related to genes found in the ancestors of modern mitochondria and chloroplasts and their presence is easily explained by transfer from the organelle to the nucleus. Eukaryotic genomes also contain examples of transposons that have been acquired from bacteria. That's also easy to understand because we know how transposons jump between species.

The literature on eukaryotic genomes is full of additional claims of LGT from bacteria (and other eukaryotes) but many of those have subsequently been attributed to contamination of genomic DNA [see Contaminated genome sequences]. Nevertheless, it's commonly accepted that lateral gene transfer from bacteria to eukaryotes is real and each new eukaryotic genome has several hundred genes acquired from bacteria. It usually accounts for about 1% of the genome. For example, even after extensive analysis of tardigrade genome sequences, there's still somewhere between 1% and 2% HGT/LGT (Yoshida et al., 2017).

An extensive analysis of the finished human genome sequence still suggested that there were 145 genes derived from LGT (Crisp et al., 2015). Those same authors claim to have detected a low level of LGT/HGT in dozens of other eukaryotic species. Here's what they say in their abstract ...

We have taken advantage of the recent availability of a sufficient number of high-quality genomes and associated transcriptomes to carry out a detailed examination of HGT in 26 animal species (10 primates, 12 flies and four nematodes) and a simplified analysis in a further 14 vertebrates. Genome-wide comparative and phylogenetic analyses show that HGT in animals typically gives rise to tens or hundreds of active ‘foreign’ genes, largely concerned with metabolism. Our analyses suggest that while fruit flies and nematodes have continued to acquire foreign genes throughout their evolution, humans and other primates have gained relatively few since their common ancestor. We also resolve the controversy surrounding previous evidence of HGT in humans and provide at least 33 new examples of horizontally acquired genes.

That result was challenged by Salzberg (2017) who presented convincing evidence that many of the LGT claims were due to contamination, or they are mitochondrial genes, or they did not meet the minimal standards for LGT claims. He says,

In this study, I re-examined the claims of Crisp et al. [1] focusing on the human genes. Instead of using a large-scale, automated analysis, which by its very nature could enrich the results for artifactual findings, I looked at each human gene individually to determine whether the evidence is sufficient to support the conclusion that HGT occurred. An important principal here is that extraordinary claims require extraordinary evidence: there is no doubt that the vast majority of human genes owe their presence in the human genome to the normal process of inheritance by vertical descent. Thus, if other, more mundane processes can explain the alignments of a human gene sequence, these explanations are far more likely than HGT.

Bill martin is also skeptical. He also claims that even a low level of LGT in eukaryotes is too much. He claims there's no solid evidence to support those claims and they persist because researchers are not thinking critically about their results and the consequences (Martin, 2017). He says,

Claims for LGT among eukaryotes essentially did not exist before we had genomes because, in contrast to prokaryotes, there are no characters known among eukaryotes that require LGT in order to explain their distribution, except perhaps the spread of plastids via secondary symbiosis. Today, claims for eukaryote LGT are common in the literature, so common that students or nonspecialists might get the impression that there is no difference between prokaryotic and eukaryotic genetics. The time has come where we need to ask whether the many claims for eukaryote LGT – prokaryote to eukaryote LGT and eukaryote to eukaryote LGT – are true.

There are several problems with these claims according to Bill Martin. First, the pattern of LGT doesn't conform to what we see in bacteria where entire clades have inherited genes transferred from bacteria. Most of the claims of LGT are confined to a single species. Second, there's no reasonable mechanism for LGT as there is in bacteria.

The reality checks are simple. If the claims are true, then we need to see evidence in eukaryotic genomes for the cumulative effects of LGT over time, as we see with pangenomes in prokaryotes, and as we see with sequence divergence. That is, the number of genes acquired by LGT needs to increase in eukaryotic lineages as a function of time. We also need to see evidence for genetic mechanisms that could spread genes across eukaryote species (and order, and phylum) boundaries, as we see in prokaryotes. If we do not see the cumulative effects, and if there are no tangible genetic mechanisms, then we have to openly ask why, and entertain the possibility that the claims might not be true. Could it be that eukaryote LGT does not really exist to any significant extent in nature, but is an artefact produced by genome analysis pipelines?

This is not a popular view. That's not surprising coming from Bill Martin because he often challenges the current dogmas. He raises an issue that's more important than the presence of LGT in eukaryotes and that's the tendency of today's scientists to adopt a consensus view without thinking critically.

Why should I care about eukaryote LGT anyway? Is not the practical solution to just believe what everyone else does and “get with the programme” as a prominent eukaryote LGT proponent recently recommended that I do (Dan Graur is my witness). At eukaryote genome meetings, where folks pride themselves on the amounts and kinds of LGT they are finding in a particular eukaryote genome (not in all genomes), I feel like Winston Smith in Orwell's novel 1984, listening to an invented truth recited by members of the Inner Party. My mentors taught me that students of the natural sciences are not obliged to get with anyone's program, instead we are supposed to think independently and always to critically inspect, and re-inspect, current premises. Doing "get with the program" science in herds can produce curious effects. For example, the well-managed ENCODE project that ascribed a function to 80% of the human genome was a textbook case of everyone "getting with the program," and everyone, however, also missing the point, obvious to evolutionary biologists, that the headline result of 80% function cannot be true.

---

Image Credit:Scientific American, Doolittle, W. (2000) Uprooting the Tree of Life. Scientific American, February 2000.

Crisp, A., Boschetti, C., Perry, M., Tunnacliffe, A., and Micklem, G. (2015) Expression of multiple horizontally acquired genes is a hallmark of both vertebrate and invertebrate genomes. Genome biology, 16:50. [doi: 10.1186/s13059-015-0607-3]

Martin, W.F. (2017) Too Much Eukaryote LGT. BioEssays, 1700115. [doi: 10.1002/bies.201700115]

Salzberg, S.L. (2017) Horizontal gene transfer is not a hallmark of the human genome. Genome biology, 18:85. [doi: 10.1186/s13059-017-1214-2]

Yoshida, Y., Koutsovoulos, G., Laetsch, D.R., Stevens, L., Kumar, S., Horikawa, D.D., Ishino, K., Komine, S., Kunieda, T., and Tomita, M. (2017) Comparative genomics of the tardigrades Hypsibius dujardini and Ramazzottius varieornatus. PLoS Biology, 15:e2002266. [doi: 10.1371/journal.pbio.2002266]