Phylogenomics of the Human Genome
Authors: Gabaldón Toni 
Published: December 2009

The availability of the complete sequence of the human genome has paved the way to investigate the evolution of our species from the perspective provided by each single gene encoded in our genome. Here I survey recent advances towards the reconstruction and analysis of the human phylome, the complete collection of molecular phylogenies reconstructed for each human protein‐coding gene. Initial analyses of such large phylogenomic dataset have not only served to produce a complete catalogue of orthologues and paralogues of human genes across 35 other eukaryotic species but also have revealed interesting evolutionary information. For instance, we could trace the history of duplication events in the lineages leading to our species and found that expansions of certain biological processes correlate with physiological adaptations experienced by our ancestors. Another interesting finding is the large degree of topological diversity found among different gene trees, emphasizing the difficulty of resolving certain evolutionary relationships.

Key concepts

Evolution by gene duplication
. Gene duplication is one of the main processes by which a genome can acquire novel functions. Several processes such as retrotransposition of messenger RNAs and the duplication of segments of a chromosome, entire chromosomes and even whole genomes, provide duplicate copies of genomic regions that constitute the raw material where evolution can act to create novel functions. The fate of most duplicate genes is to be lost by pseudogenization. However, certain mutations may generate a novel functionality in one of the duplicates or render each duplicate specialized in one of the functions carried out by the ancestor. If these changes provide selective advantages, such mutations will be selected and both gene copies will be maintained. These duplications leave a footprint in the genome that we can interpret through phylogenetic analyses. In this way we can discover when each gene family experienced duplications. Through the functional analysis of the encoded functions of families expanded at different evolutionary periods we can infer what evolutionary innovations played a role.

Species phylogeny
. The evolutionary relationship among a group of species is usually represented by species phylogeny or tree of life. Such phylogenies were historically reconstructed by grouping organisms based on morphological characters. With the advent of sequencing techniques, species phylogenies are inferred from the reconstructed evolutionary histories of genes shared by the species of interest. However, it has been found that different genes may provide conflicting topological arrangements of the species considered. Currently there is much research being done about how the information contained in entire genomes can be used to resolve particularly conflicting evolutionary relationships.

Orthology prediction
. Reliable orthology prediction, that is finding correspondences among genes in different genomes, is central to comparative genomics. Most automated methods to predict orthology are based on pair‐wise comparisons, for instance finding pairs of genes in different genomes that are, reciprocally, most similar to each other. However, orthology is defined by phylogenetic criteria and therefore inspecting the evolutionary history of a gene family would be the most appropriate way to unravel orthology relationships. Automated phylogeny‐based orthology prediction has recently emerged as a feasible alternative for genome‐wide studies. The species‐overlap algorithm used in this study was specifically designed to cope with the large topological diversity found among gene trees.