Characterizing gene family evolution

Abstract

Gene families are widely used in comparative genomics, molecular evolution, and in systematics. However, they are constructed in different manners, their data analyzed and interpreted differently, with different underlying assumptions, leading to sometimes divergent conclusions. In systematics, concepts like monophyly and the dichotomy between homoplasy and homology have been central to the analysis of phylogenies. We critique the traditional use of such concepts as applied to gene families and give examples of incorrect inferences they may lead to. Operational definitions that have emerged within functional genomics are contrasted with the common formal definitions derived from systematics. Lastly, we question the utility of layers of homology and the meaning of homology at the character state level in the context of sequence evolution. From this, we move forward to present an idealized strategy for characterizing gene family evolution for both systematic and functional purposes, including recent methodological improvements.

Keywords: evolution, molecular; genomics; phylogeny; sequence homology.

Fig. 1:

A tree derived from Fletcher et al., 2001 as visualized with TreeView (38) shows the relationship of a C-type lectin subfamily with a subset of teleost fish sequences and the three known instances of neofunctionalization leading to an antifreeze protein. There is strong phylogenetic support for independent evolution of AFP (anti freeze protein) from an ancestral C-type lectin (CL). That this neofunctionalization has happened multiple times probably indicates a propensity for this sequence and fold to neofunctionalize in that way, but does change the sequence or functional relationships of ancestral C-type lectin molecules to each other.

Fig. 2

An evolutionary trajectory of homologous sites leading to parallel evolution and to divergent followed by convergent evolution, both generating homoplasy, is shown. Such a substitution pattern is not particularly improbable under many models of sequence evolution and can readily be found across gene families. The resulting alignments corresponding to homology and the non-homologous alternative are shown below. No standard multiple sequence alignment program will produce the alignment indicative of non-homology and this alignment is not reflective of the evolutionary history of the character. However, the non-homologous treatment is the logical conclusion of considering homoplasious sites to be nonhomologous.

Fig. 3

A flowchart for the generation and analysis of gene families is depicted. This includes applications in both systematics and functional biology.