Evolutionary genomics of the Fox genes: Origin of gene families and the ancestry of gene clusters

Abstract

Over the past decade genomic approaches have begun to revolutionise the study of animal diversity. In particular, genome sequencing programmes have spread beyond the traditional model species to encompass an increasing diversity of animals from many different phyla, as well as unicellular eukaryotes that are closely related to the animals. Whole genome sequences allow researchers to establish, with reasonable confidence, the full complement of any particular family of genes in a genome. Comparison of gene complements from appropriate genomes can reveal the evolutionary history of gene families, indicating when both gene diversification and gene loss have occurred. More than that, however, assembled genomes allow the genomic environment in which individual genes are found to be analysed and compared between species. This can reveal how gene diversification occurred. Here, we focus on the Fox genes, drawing from multiple animal genomes to develop an evolutionary framework explaining the timing and mechanism of origin of the diversity of animal Fox genes. Ancient linkages between genes are a prominent feature of the Fox genes, depicting a history of gene clusters, some of which may be relevant to understanding Fox gene function.

Foxk1 promotes cell proliferation and represses myogenic differentiation by regulating Foxo4 and Mef2 factors

“…To date there are more than 300 members that belong to the forkhead/winged helix transcription factor family based on relative homology of a 110 amino acid DNA-binding domain (also referred to as winged helix domain) since the discovery of the original member Fkh in Drosophila (Clark et al, 1993;Shimeld et al, 2010;Weigel and Jäckle, 1990;Weigel et al, 1989). Many of the forkhead/winged helix factors bind directly to cognate binding motifs of genes and transactivate or repress gene expression (Wijchers et al, 2006 …”

Too many ways to make a muscle: Evolution of GRNs governing myogenesis

“…FoxF and FoxC orthologs are highly conserved classes among diverse metazoans and they are clustered in both protostomes and deuterostomes together with FoxQ and FoxL genes (Mazet et al, 2006;Shimeld et al, 2010). This cluster was probably ancestrally expressed in the developing endo-mesodermal derivatives; given that all these Fox genes show conserved expression in developing endo-mesodermal tissues and play roles in mesoderm differentiation and muscle development.…”

DNA-binding specificity changes in the evolution of forkhead transcription factors

“…The Fox family of TFs shares a conserved DBD that is structurally identifiable as a subgroup of the much larger winged helix superfamily, which includes both sequence-specific DNA-binding proteins and linker histones, which appear to bind DNA nonspecifically (4,5). Proteins with unambiguous sequence homology to the forkhead domain are present throughout opisthokontsthe phylogenetic grouping that includes all descendants of the last common ancestor of animals and fungi-but have diverged so extensively over approximately 1 billion years of evolution that distantly related Fox proteins are not generally alignable outside the forkhead domain (6,7). Moreover, distantly related Fox-like domains have been found in Amoebozoa, a sister group to opisthokonts (8).…”