Evolution of Homeobox Gene Clusters in Animals: The Giga-Cluster and Primary vs. Secondary Clustering

Abstract

The Hox gene cluster has been a major focus in evolutionary developmental biology. This is because of its key role in patterning animal development and widespread examples of changes in Hox genes being linked to the evolution of animal body plans and morphologies. Also, the distinctive organization of the Hox genes into genomic clusters in which the order of the genes along the chromosome corresponds to the order of their activity along the embryo, or during a developmental process, has been a further source of great interest. This is known as collinearity, and it provides a clear link between genome organization and the regulation of genes during development, with distinctive changes marking evolutionary transitions. The Hox genes are not alone, however. The homeobox genes are a large super-class, of which the Hox genes are only a small subset, and an ever-increasing number of further gene clusters besides the Hox are being discovered. This is of great interest because of the potential for such gene clusters to help understand major evolutionary transitions, both in terms of changes to development and morphology as well as evolution of genome organization. However, there is uncertainty in our understanding of homeobox gene cluster evolution at present. This relates to our still rudimentary understanding of the dynamics of genome rearrangements and evolution over the evolutionary timescales being considered when we compare lineages from across the animal kingdom. A major goal is to deduce whether particular instances of clustering are primary (conserved from ancient ancestral clusters) or secondary (reassortment of genes into clusters in lineage-specific fashion). The following summary of the various instances of homeobox gene clusters in animals, and the hypotheses about their evolution, provides a framework for the future resolution of this uncertainty.

Bsx controls pineal complex development

“…Analysis of flh and bsx double-mutant embryos revealed that Flh and Bsx act in parallel in specification of the pineal anlage, because only double mutants lacked otx5 expression completely, suggesting an absence of PhR cells. The transcription factor Flh can be grouped together with Bsx into the ANTP class of homeodomain proteins (Ferrier, 2016), and might share target specificity, providing a potential molecular basis for partial redundancy of both transcription factors.…”

Dynamics of genomic innovation in the unicellular ancestry of animals

“…Suggestively, detailed analyses of the transcriptomic and proteomic regulatory dynamics of Capsaspora and Salpingoeca showed that these genes are frequently implicated in the transition to life stages reminiscent of multicellularity – aggregative in Capsaspora ( Sebé-Pedrós et al, 2013 , Sebé-Pedrós et al, 2016a ), and clonal colonies in Salpingoeca ( Fairclough et al, 2013 ). Furthermore, the genome architectures of extant Metazoa are, in many aspects, markedly different from most other eukaryotes: they have larger genomes ( Elliott and Gregory, 2015a ), containing more ( Csuros et al, 2011 ) and longer introns ( Elliott and Gregory, 2015a ) that can sustain alternative splicing-rich transcriptomes ( McGuire et al, 2008 ; Irimia and Roy, 2014 ), have richer complements of repetitive sequences such as transposable elements ( Elliott and Gregory, 2015b ) and are structured in ancient patterns of gene linkage associated with transcriptional co-regulation ( Irimia et al, 2012 ; Simakov et al, 2013 ) – e.g., the Homeobox clusters ( Ferrier, 2016 ). The relationship between these patterns of genome evolution and multicellularity is, however, unclear: these traits are not exclusive of animals ( cf.…”

A novel homology-based algorithm for the identification of physically linked clusters of paralogous genes

“…For example, by using previously known sequences of the prolactin gene cluster in mouse, CGPFinder was able to find novel prolactin CGPs in goat and sheep (Supplemental data; Supplemental Table S2), providing further evidence supporting the independent evolution of prolactin clusters in ruminants and rodents (Miller & Eberhardt, 1983). Thus, coupled with robust phylogenetic analysis at the gene and species levels, CGPFinder could be very useful for distinguishing between different types of clusters (e.g., primary, secondary, and independently evolved) comprised of paralogous genes and the evolutionary history of their assemblies (Ferrier, 2016).…”