Non-collinear Hox gene expression in bivalves and the evolution of morphological novelties in mollusks

Hox genes are key developmental regulators that are involved in establishing morphological features during animal ontogeny. They are commonly expressed along the anterior–posterior axis in a staggered, or collinear, fashion. In mollusks, the repertoire of body plans is widely diverse and current data suggest their involvement during development of landmark morphological traits in Conchifera, one of the two major lineages that comprises those taxa that originated from a uni-shelled ancestor (Monoplacophora, Gastropoda, Cephalopoda, Scaphopoda, Bivalvia). For most clades, and bivalves in particular, data on Hox gene expression throughout ontogeny are scarce. We thus investigated Hox expression during development of the quagga mussel, Dreissena rostriformis, to elucidate to which degree they might contribute to specific phenotypic traits as in other conchiferans. The Hox/ParaHox complement of Mollusca typically comprises 14 genes, 13 of which are present in bivalve genomes including Dreissena. We describe here expression of 9 Hox genes and the ParaHox gene Xlox during Dreissena development. Hox expression in Dreissena is first detected in the gastrula stage with widely overlapping expression domains of most genes. In the trochophore stage, Hox gene expression shifts towards more compact, largely mesodermal domains. Only few of these domains can be assigned to specific developing morphological structures such as Hox1 in the shell field and Xlox in the hindgut. We did not find traces of spatial or temporal staggered expression of Hox genes in Dreissena. Our data support the notion that Hox gene expression has been coopted independently, and to varying degrees, into lineage-specific structures in the respective conchiferan clades. The non-collinear mode of Hox expression in Dreissena might be a result of the low degree of body plan regionalization along the bivalve anterior–posterior axis as exemplified by the lack of key morphological traits such as a distinct head, cephalic tentacles, radula apparatus, and a simplified central nervous system.

The ParaHox gene Cdx4 induces acute erythroid leukemia in mice

Key Points CDX4 induces AEL in mice and suppresses expression of genes associated with erythroid differentiation. Mutations detectable in the Cdx4-induced AEL model occur in genes reported mutated in patients with AEL.

Comparative Phylogenomic Synteny Network Analysis of Mammalian and Angiosperm Genomes

BackgroundSynteny analysis is a valuable approach for understanding eukaryotic gene and genome evolution, but still relies largely on pairwise or reference-based comparisons. Network approaches can be utilized to expand large-scale phylogenomic microsynteny studies. There is now a wealth of completed mammalian (animal) and angiosperm (plant) genomes, two very important lineages that have evolved and radiated over the last ~170 million years. Genomic organization and conservation differs greatly between these two groups; however, a systematic and comparative characterization of synteny between the two lineages using the same approaches and metrics has not been undertaken.ResultsWe have built complete microsynteny networks for 87 mammalian and 107 angiosperm genomes, which contain 1,464,753 nodes (genes) and 49,426,268 edges (syntenic connections between genes) for mammals, and 2,234,461 nodes and 46,938,272 edges for angiosperms, respectively. Exploiting network statistics, we present the functional characteristics of extremely conserved and diversified gene families. We summarize the features of all syntenic gene clusters and present lineage-wide phylogenetic profiling, revealing intriguing sub-clade lineage-specific clusters. We depict several representative clusters of important developmental genes in humans, such as CENPJ, p53 and NFE2. Finally, we present the complete homeobox gene family networks for both mammals (including Hox and ParaHox gene clusters) and angiosperms.ConclusionsOur results illustrate and quantify overall synteny conservation and diversification properties of all annotated genes for mammals and angiosperms and show that plant genomes are in general more dynamic.

Lampreys, the jawless vertebrates, contain only two ParaHox gene clusters

ParaHox genes (Gsx, Pdx, and Cdx) are an ancient family of developmental genes closely related to the Hox genes. They play critical roles in the patterning of brain and gut. The basal chordate, amphioxus, contains a single ParaHox cluster comprising one member of each family, whereas nonteleost jawed vertebrates contain four ParaHox genomic loci with six or seven ParaHox genes. Teleosts, which have experienced an additional whole-genome duplication, contain six ParaHox genomic loci with six ParaHox genes. Jawless vertebrates, represented by lampreys and hagfish, are the most ancient group of vertebrates and are crucial for understanding the origin and evolution of vertebrate gene families. We have previously shown that lampreys contain six Hox gene loci. Here we report that lampreys contain only two ParaHox gene clusters (designated as α- and β-clusters) bearing five ParaHox genes (Gsxα, Pdxα, Cdxα, Gsxβ, and Cdxβ). The order and orientation of the three genes in the α-cluster are identical to that of the single cluster in amphioxus. However, the orientation of Gsxβ in the β-cluster is inverted. Interestingly, Gsxβ is expressed in the eye, unlike its homologs in jawed vertebrates, which are expressed mainly in the brain. The lamprey Pdxα is expressed in the pancreas similar to jawed vertebrate Pdx genes, indicating that the pancreatic expression of Pdx was acquired before the divergence of jawless and jawed vertebrate lineages. It is likely that the lamprey Pdxα plays a crucial role in pancreas specification and insulin production similar to the Pdx of jawed vertebrates.

Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster

The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1. The sequence of sand rat Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests that mutational heterogeneity within genomes could influence the course of evolution.

Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster

The sand rat Psammomys obesus is a gerbil native to deserts of North Africa and the Middle East1. Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese and develop type II diabetes2 which, in extreme cases, leads to pancreatic failure and death3,4. Previous studies have reported inability to detect the Pdx1 gene or protein in gerbils5–7, suggesting that absence of this key insulin-regulating homeobox gene might underlie diabetes susceptibility. Here we report sequencing of the sand rat genome and discovery of an extensive, mutationally-biased GC-rich genomic domain encompassing many essential genes, including the elusive Pdx1. The sequence of Pdx1 has been grossly affected by GC-biased mutation leading to the highest divergence observed in the animal kingdom. In addition to molecular insights into restricted caloric intake in a desert species, the discovery that specific chromosomal regions can be subject to elevated mutation rate has widespread significance to evolution.