The Use of Orthologous Sequences to Predict the Impact of Amino Acid Substitutions on Protein Function
Figure 3
Phylogenetic tree and ancestral allele determination from orthologs of human MTHFR.
Tree: MTHFR sequences from modern-day species are indicated. Database identifiers for these entries are listed in Table S2. Gene duplication events are shown with orange circles, and speciation events with green circles. Nodes numbered in red correspond to ancestral branch points in the human MTHFR lineage. Longer branch lengths indicate faster evolutionary rate. The chicken sequence was given an arbitrary, long branch length because it is a sequence fragment and the actual branch length could not be accurately determined. Ancestral allele determinations: The right columns show the amino acids found in the modern-day sequences corresponding to positions 134, 240 and 294 in human MTHFR. These are shown to illustrate how ancestral sites are determined and, consequently, how long the identity of the site in the human enzyme has been preserved in the human lineage (see text for details).
