Gene phylogenies and protein–protein interactions: possible artifacts resulting from shared protein interaction partners

Abstract

The study of gene families critically depends on the correct reconstruction of gene genealogies, as for instance in the case of transcription factor genes like Hox genes and Dlx gene families. Proteins belonging to the same family are likely to share some of the same protein interaction partners and may thus face a similar selective environment. This common selective environment can induce co-evolutionary pressures and thus can give rise to correlated rates and patterns of evolution among members of a gene family. In this study we simulate the evolution of a family of sequences which share a set of interaction partners. Depending on the amount of sequence dedicated to protein-protein interaction and the relative rate parameters of sequence evolution three outcomes are possible: if the fraction of the sequence dedicated to interaction with common co-factors is low and the time since divergence is small, the trees based on sequence information tend to be correct. If the time since gene duplication is long two possible outcomes are observed in our simulations. If the rate of evolution of the interaction partner is small compared to the rate of evolution of the focal protein family, the reconstructed trees tend towards star phylogenies. As the rate of evolution of the interaction partner approaches that of the focal protein family the reconstructed phylogenies tend to be incorrectly resolved. We conclude that the genealogies of gene families can be hard to estimate, in particular if the proteins interact with a conserved set of binding partners, as is likely the case for transcription factors.

The amphioxus Hox cluster: characterization, comparative genomics, and evolution

“…The only prominent differences are the introns of the posterior AmphiHox14-AmphiHox10 genes, which are much longer than the introns of posterior vertebrate Hox genes (Supplemental Material). Note, however, that we do not know whether the genes with the same PG designation in amphioxus and vertebrates are true orthologs or whether they arose from an independent expansion of the cluster (Ferrier et al, 2000;Campos et al, 2004;Ferrier, 2004;Powers and Amemiya, 2004). This issue may well be impossible to resolve with phylogenies owing to the extent of sequence divergence between the genes in question.…”

“…In most phylogenetic analyses, the posterior AmphiHox genes neither group unambiguously with the corresponding paralog groups (PG) of vertebrates nor support clearly independent duplication events; see e.g. Ferrier et al (2000), Campos et al (2004), Ferrier (2004, Peterson (2004), and Cameron et al (2006). Despite the discovery of PG14 genes in some vertebrates (Powers and Amemiya, 2004), the question is still open how exactly the posterior genes AmphiHox14-AmphiHox10 are related to the vertebrate PG14-PG10 Hox genes.…”

A Conserved Mammalian Protein Interaction Network

“…In fact, under some models, such co-evolution may be sufficient to result in misleading phylogenetic signals due to correlated substitutions between interacting proteins [31]. Here again, however, the fact that interacting proteins also tend to be co-expressed may drive the similarities in rates of evolution [32].…”

Evolutionary Biology: Biodiversification from Genotype to Phenotype

“…Such coevolution has relevance for other fields as well: For instance, it can interfere with sequence divergence in such a manner as to give misleading phylogenetic signals(Campos et al 2004).…”