Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus ( Branchiostoma lanceolatum ) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis -regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that—in vertebrates—over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.

All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

Brain function requires neuronal activity-dependent energy consumption. neuronal energy supply is controlled by molecular mechanisms that regulate mitochondrial dynamics, including Kinesin motors and mitofusins, miro1-2 and Trak2 proteins. Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. This family of proteins is encoded by an array of armadillo (Arm) repeat-containing genes located on the X chromosome. The Armcx cluster is unique to Eutherian mammals and evolved from a single ancestor gene (Armc10). We show that these genes are highly expressed in the developing and adult nervous system. Furthermore, we demonstrate that Armcx3 expression levels regulate mitochondrial dynamics and trafficking in neurons, and that Alex3 interacts with the Kinesin/miro/Trak2 complex in a Ca 2 + -dependent manner. our data provide evidence of a new Eutherian-specific family of mitochondrial proteins that controls mitochondrial dynamics and indicate that this key process is differentially regulated in the brain of higher vertebrates.

An important question in biology is why some animals are able to regenerate, whereas others are not. The basal chordate amphioxus is uniquely positioned to address the evolution of regeneration. We report here the high regeneration potential of the European amphioxus Branchiostoma lanceolatum. Adults regenerate both anterior and posterior structures, including neural tube, notochord, fin, and muscle. Development of a classifier based on tail regeneration profiles predicts the assignment of young and old adults to their own class with >94% accuracy. The process involves loss of differentiated characteristics, formation of an msx-expressing blastema, and neurogenesis. Moreover, regeneration is linked to the activation of satellite-like Pax3/7 progenitor cells, the extent of which declines with size and age. Our results provide a framework for understanding the evolution and diversity of regeneration mechanisms in vertebrates.invertebrate chordate-vertebrate transition | stem cells | cephalochordate R egeneration, as an evolutionary trait, is distributed widely and nonuniformly across the Metazoa; it is also highly variable in quality and structural specificity. Recently, there has been a resurgence of interest in the evolutionary distribution and basis of regeneration (1). A question of general interest is why certain lineages have lost or reduced regenerative capacity relative to their regeneration-competent sister taxa. In particular, the properties of CNS regeneration in more basal vertebrates may shed light on the reasons for reduced capacity in mammals and birds (2). Despite the plethora of hypotheses that attempt to explain the evolutionary significance of regenerative ability, the unresolved central issue is whether the ability to regenerate is adaptive or simply a byproduct of selection on other metabolic or developmental processes.Studies across phyla indicate that there is broad conservation of the developmental signaling pathways involved in regeneration (3), but the signals that initiate regeneration on injury and the downstream targets that they induce have proven more elusive. Moreover, the historical distinction between invertebrate-and vertebrate-type regeneration can make comparisons difficult. In planaria and Hydra, for example, the contribution of pluripotent stem cells has been the predominant focus of regeneration research. In contrast, among vertebrate models, studies have highlighted dedifferentiation of existing structures or the role of muscle satellite cells (3). Bridging the gap, ambulacrarian deuterostomes and urochordates show considerable regenerative capacity (1, 4-6) (Fig. 1A). However, their anatomy is not readily comparable with the vertebrate body plan, making it difficult to draw conclusions from such derived phyla. The origins and evolution of chordate regeneration mechanisms are, therefore, still unresolved.The cephalochordate amphioxus, the most basal living chordate (7), possesses many ancestral anatomical characters, whereas many derived vertebrate features, such as bona fi...