Horizontal gene transfer (HGT), also known as lateral gene transfer, refers to the movement of genetic infor- mation across normal mating barriers, between more or less distantly related organisms, and thus stands in distinction to the standard vertical transmission of genes from parent to offspring. Extant eukaryotes arose by HGT on the grandest scale possible — the endosymbiosis and subsequent genetic integration of entire organisms that gave rise to the mitochondrion and t he plastid. However, the impor- tance of subsequent, ongoing HGT in eukaryotes has been under-appreciated since the outset of the genomics era for a variety of reasons. First, the early recognition of the importance of HGT in bacterial evolution, and con- tinuing debate about exactly how profound this has be en (see REFS 1–6for examples), have overshadowed the role of HGT in eukaryotes. Second, most of the earliest and even the most current evidence for HGT in eukaryo- tes comes from protists, whereas most biologists study animals (or at least plants or fungi) and therefore often overlook, or dismiss as insignificantly aberrant, findings from such obscure creatures. Lastly, the erroneous report of substantial HGT in the human genome 7–9 has prob- ably chilled the field, tarnished more credible claims for eukaryotic HGT, and possibly inhibited scientists from looking for HGT in the many subsequently sequenced animal genomes, and perhaps even in fungal and plant genomes. Nevertheless, HGT has altered our concepts of the genome, the species and the tree (or web) of life in the bacterial world, and now cases of HGT in eukaryotes are emerging at an increasing rate and account for many adaptively important traits. Indeed, the number of cases of HGT involving eukaryotes is now so great that it no longer makes sense to attempt to comprehen- sively compile individual cases, as has been done in past reviews 10–12 . Instead, we will use selected examples to highlight emerging trends and questions. Detecting and evaluating cases of HGT Several approaches can lead to the suspicion that HGT has occurred, but so-called ‘surrogate’ methods 13 t o identify potential cases of HGT are insufficient unless followed up by formal phylogenetic analysis. The widely publicized but overstated claim in 2001 that the draft human genome contained about one hundred genes acquired from bacteria at the onset of or during verte- brate evolution 7 illustrates this problem: top BLAST hits were used to identify human genes, the closest ‘relatives’ of which were bacterial homologues, but subsequent phylogenetic analysis often negated this relationship 9 . HGT was also inferred (along with the alternative pos- sibility of massive gene loss) for cases in which human genes had homologues in bacteria but not in the then four other ‘completely’ sequenced eukaryotic genomes 7 . These cases were undermined by finding closer homo- logues in incompletely sequenced eukaryotic genomes, supporting gene loss 8,14 . The gold standard for identifying HGT with con- fidence is phylogenetic incongruence — this occurs if there is strong conflict between the phylogenies of the gene and of the organism. Even then, several potentially confounding factors must still be taken into account. Although our understanding of eukaryotic phylogeny *Department of Botany, Univers ity of British Columbia, Vancouver, British Columbia V6T 1Z, Canada. ‡ Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. Correspondence to P.J.K. e-mail: pkeeling@inter change.ubc .ca doi:10.1038/nrg2386 Published online 1 July 2008 Horizontal gene transfer in eukaryotic evolution Patrick J. Keeling* and Jeffrey D. Palmer‡ Abstract | Horizontal gene transfer (HGT; also known as lateral gene transfer) has had an important role in eukaryotic genome evolution, but its importance is often overshadowed by the greater prevalence and our more advanced understanding of gene transfer in prokaryotes. Recurrent endosymbioses and the generally poor sampling of most nuclear genes from diverse lineages have also complicated the search for transferred genes. Nevertheless, the number of well-supported cases of transfer from both prokaryotes and eukaryotes, many with significant functional implications, is now expanding rapidly. Major recent trends include the important role of HGT in adaptation to certain specialized niches and the highly variable impact of HGT in different lineages. REVIEWS NATURE REVIEWS |GENETICSVOLUME 9 |AUGUST 2008 |605
