The Tree of Life Concept in the Age of Genomics

The concept of the TOL introduced by Darwin, captured in the famous single illustration of the On the Origin of Species (Darwin 1859), and used by Haeckel as the grand scheme of the history of the actual life-forms is the cornerstone of evolutionary biology and, arguably, of biology in general. For nearly 140 years after the publication of the Origin, phylogenetic trees, which were initially constructed using phenotypic characters but, following the seminal work of Zuckerkandl and Pauling (1962, 1965), increasingly relied on molecular sequence comparison, were viewed as a (more or less accurate) depiction of the evolution of the respective organisms. In other words, a tree built for a specific character or a gene was routinely equated with a “species tree.” The use of rRNA as the molecule of choice for phylogenetic reconstruction culminated in the now textbook three-domain TOL of Woese and coworkers (Pace et al. 1986; Woese 1987) and was the brilliant culmination of the heroic period of phylogenetics that brought hopes that the detailed, definitive topology of the TOL could be within reach. Trouble for the TOL concept, however, started even before the advent of genomics as it became clear that common and essential genes of prokaryotes experienced multiple HGTs. So the idea of a “net of life” as a potential replacement for the TOL was proposed (Hilario and Gogarten 1993; Gogarten 1995). Generally, however, in the pregenomic era, HGT was viewed as a minor process of evolution, crucial in some areas such as the spread of antibiotic resistance but secondary for the general scheme of evolution. In the late 1990s, comparative genomics of prokaryotes dramatically changed this picture by showing that the patterns of gene distribution across genomes were typically patchy, whereas the topologies of gene-specific phylogenetic trees were often incongruent. These findings indicated that HGT was extremely common among prokaryotes (bacteria and archaea) (Doolittle 1999a,b, 2000; Martin 1999; Koonin et al. 2001; Gogarten et al. 2002; Koonin and Aravind 2002; Lawrence and Hen drick son 2003; Gogarten and Townsend 2005; Dagan et al. 2008) and could have been important also in the evolution of eukaryotes, especially, as a consequence of endosymbiotic events (Doolittle 1998; Martin and Herr mann 1998; Doolittle et al. 2003; Embley and Martin 2006). Thus, a perfect TOL turned out to be a chimera because extensive HGT prevents any single gene tree from being an accurate representation of the evolution of entire genomes. The realization that HGT among pro kar y otes is the dominant rather than an exceptional mode of evolution led to the idea of “uprooting” the TOL, a development that is often interpreted as a paradigm shift in evolutionary biology (Pennisi 1999; Doolittle 2000; O’Malley and Boucher 2005). Of course, the incongruence of gene phylogenies caused by HGT or other processes cannot alter the fact that all cellular life-forms are linked by a tree of cell divisions (Omnis cellula e cellula, according to the famous motto of Rudolf Virchow [1858]) that goes back to the earliest stages of evolution, with the exception of endosymbiotic events that were key to the evolution of eukaryotes but not prokaryotes (Lane and Archibald 2008). The problems with the TOL concept in the era of comparative genomics concern the TOL as it can be derived by the phylogenetic (phylogenomic) analysis of genes and genomes. Thus, the claim that HGT uproots the TOL more accurately means that extensive HGT has the potential to result in complete decoupling of molecular phylogenies from the actual tree of cells. Phylogenetic trees of genes also reflect the evoluThe Phylogenetic Forest and the Quest for the Elusive Tree of Life