Figure 1. Three hypothetical gene histories that give rise to a significant sequence similarity between a human gene and a bacterial gene. The length of the branches is proportional to evolutionary change. The best hit for the human gene will be to the sequence to which the sum of the branch lengths is the smallest (bacteria 1 in all three cases). A×over a branch and a name within parentheses indicate gene loss in that lineage. (a) Unequal rate of evolution may cause the human gene to have a significantly higher sequence similarity to a bacterial gene than to other eukaryotic genes although the phylogenetic tree shows that human gene is more closely related to the other eukaryotes than to bacteria. (b) Loss of the gene in all other eukaryotic lineages except vertebrates causes the human gene to be uniquely shared between humans and bacteria although the gene was present in the last common eukaryotic ancestor. Note that the human gene is attached to the root of the bacteria. (c) A horizontal gene transfer from bacteria to the ancestor of humans after the divergence of vertebrates from other eukaryotes results in a phylogenetic tree where the human gene is nested within the bacteria.