Universal nomenclature for oxytocin–vasotocin ligand and receptor families

Oxytocin (OXT; hereafter OT) and arginine vasopressin or vasotocin (AVP or VT; hereafter VT) are neurotransmitter ligands that function through specific receptors to control diverse functions1,2. Here we performed genomic analyses on 35 species that span all major vertebrate lineages, including newly generated high-contiguity assemblies from the Vertebrate Genomes Project3,4. Our findings support the claim5 that OT (also known as OXT) and VT (also known as AVP) are adjacent paralogous genes that have resulted from a local duplication, which we infer was through DNA transposable elements near the origin of vertebrates and in which VT retained more of the parental sequence. We identified six major oxytocin–vasotocin receptors among vertebrates. We propose that all six of these receptors arose from a single receptor that was shared with the common ancestor of invertebrates, through a combination of whole-genome and large segmental duplications. We propose a universal nomenclature based on evolutionary relationships for the genes that encode these receptors, in which the genes are given the same orthologous names across vertebrates and paralogous names relative to each other. This nomenclature avoids confusion due to differential naming in the pre-genomic era and incomplete genome assemblies, furthers our understanding of the evolution of these genes, aids in the translation of findings across species and serves as a model for other gene families.

A local duplication of the Melanocortin receptor 1 locus in Astyanax

In this study, we report evidence of a novel duplication of Melanocortin receptor 1 (Mc1r) in the cavefish genome. This locus was discovered following the observation of excessive allelic diversity in a ∼820 bp fragment of Mc1r amplified via degenerate PCR from a natural population of Astyanax aeneus fish from Guerrero, Mexico. The cavefish genome reveals the presence of two closely related Mc1r open reading frames separated by a 1.46 kb intergenic region. One open reading frame corresponds to the previously reported Mc1r receptor, and the other open reading frame (duplicate copy) is 975 bp in length, encoding a receptor of 325 amino acids. Sequence similarity analyses position both copies in the syntenic region of the single Mc1r locus in 16 representative craniate genomes spanning bony fish (including Astyanax) to mammals, suggesting we discovered tandem duplicates of this important gene. The two Mc1r copies share ∼89% sequence similarity and, within Astyanax, are more similar to one another compared to other melanocortin family members. Future studies will inform the precise functional significance of the duplicated Mc1r locus and if this novel copy number variant may have adaptive significance for the Astyanax lineage.

Double maternal effect: duplicated nucleoplasmin 2 genes,npm2aandnpm2b, are shared by fish and tetrapods, and have distinct and essential roles in early embryogenesis

Nucleoplasmin 2(npm2) is an essential maternal-effect gene that mediates early embryonic events through its function as a histone chaperone that remodels chromatin. Here we report the existence of twonpm2(npm2aandnpm2b) genes in zebrafish. We examined the evolution ofnpm2aandnpm2bin a variety of vertebrates, their potential phylogenetic relationships, and their biological functions using knockout models via the CRISPR/cas9 system. We demonstrated that the twonpm2duplicates exist in a wide range of vertebrates, including sharks, ray-finned fish, amphibians, and sauropsids, whilenpm2awas lost in Coelacanth and mammals, as well as some specific teleost lineages. Using phylogeny and synteny analyses, we traced their origins to the early stages of vertebrate evolution. Our findings suggested thatnpm2aandnpm2bresulted from an ancient local gene duplication, and their functions diverged although key protein domains were conserved. We then investigated their functions by examining their tissue distribution in a wide variety of species and found that they shared ovarian-specific expression, a key feature of maternal-effect genes. We also showed that bothnpm2aandnpm2bare maternally-inherited transcripts in vertebrates. Moreover, we used zebrafish knockouts to demonstrate thatnpm2aandnpm2bplay essential, but distinct, roles in early embryogenesis.npm2afunctions very early during embryogenesis, at or immediately after fertilization, whilenpm2bis involved in processes leading up to or during zygotic genome activation. These novel findings will broaden our knowledge on the evolutionary diversity of maternal-effect genes and underlying mechanisms that contribute to vertebrate reproductive success.Author SummaryThe protein and transcript of thenpm2gene have been previously demonstrated as maternal contributions to embryos of several vertebrates. Recently, twonpm2genes, denoted here asnpm2aandnpm2b, were discovered in zebrafish. This study was conducted to explore the evolutionary origin and changes that occurred that culminated in their current functions. We found that an ancient local duplication of the ancestralnpm2gene created the current two forms, and while most vertebrates retained both genes, notably, mammals and certain species of fish lostnpm2aand, albeit rarely, bothnpm2aandnpm2b. Our functional analyses showed thatnpm2aandnpm2bhave diverse but essential functions during embryogenesis, asnpm2amutants failed to undergo development at the earliest stage whilenpm2bmutants developed, although abnormally, until the zygotic genome activation stage after which their development was arrested followed subsequently by death. Our study is the first to clearly demonstrate the evolution, diversification, and functional analyses of thenpm2genes, which are essential maternal factors that are required for proper embryonic development and survival.

60 YEARS OF POMC: POMC: an evolutionary perspective

Proopiomelanocortin (POMC) is a complex precursor that comprises several peptidic hormones, including melanocyte-stimulating hormones (MSHs), adrenocorticotropic hormone (ACTH), and β-endorphin. POMC belongs to the opioid/orphanin gene family, whose precursors include either opioid (YGGF) or the orphanin/nociceptin core sequences (FGGF). This gene family diversified during early tetraploidizations of the vertebrate genome to generate four different precursors: proenkephalin (PENK), prodynorphin (PDYN), and nociceptin/proorphanin (PNOC) as well as POMC, although both PNOC and POMC seem to have arisen due to a local duplication event. POMC underwent complex evolutionary processes, including internal tandem duplications and putative coevolutionary events. Controversial and conflicting hypotheses have emerged concerning the sequenced genomes. In this article, we summarize the different evolutionary hypotheses proposed for POMC evolution.

Transposable Elements Are a Significant Contributor to Tandem Repeats in the Human Genome

Sequence repeats are an important phenomenon in the human genome, playing important roles in genomic alteration often with phenotypic consequences. The two major types of repeat elements in the human genome are tandem repeats (TRs) including microsatellites, minisatellites, and satellites and transposable elements (TEs). So far, very little has been known about the relationship between these two types of repeats. In this study, we identified TRs that are derived from TEs either based on sequence similarity or overlapping genomic positions. We then analyzed the distribution of these TRs among TE families/subfamilies. Our study shows that at least 7,276 TRs or 23% of all minisatellites/satellites is derived from TEs, contributing ∼0.32% of the human genome. TRs seem to be generated more likely from younger/more active TEs, and once initiated they are expanded with time via local duplication of the repeat units. The currently postulated mechanisms for origin of TRs can explain only 6% of all TE-derived TRs, indicating the presence of one or more yet to be identified mechanisms for the initiation of such repeats. Our result suggests that TEs are contributing to genome expansion and alteration not only by transposition but also by generating tandem repeats.

Smart Nearest Neighbors

This document presents an implementation of two algorithms, Voronoi Neighbors and Binary Space Partition (BSP) Neighbors. These algorithms find neighbors of a point in a point set that are somehow better'' than aK nearest neighbors’’ or a ``all neighbors within a radius’’ query. This type of nearest neighbor query is more computationally expensive, but results in set of neighbors with more desirable properties. The BSP Neighbors search ensures that there is less local duplication, while the Voronoi Neighbors search ensures that the spatial arrangement of the neighbors is as uniform as possible.These algorithms are explained in ``Point Primitives for Interactive Modeling and Processing of 3D Geometry’’.The code is available here: https://github.com/daviddoria/SmartNearestNeighbors

Evidence and structural mechanism for late lung alveolarization

According to the current view, the formation of new alveolar septa from preexisting ones ceases due to the reduction of a double- to a single-layered capillaries network inside the alveolar septa (microvasculature maturation postnatal days 14– 21 in rats). We challenged this view by measuring stereologically the appearance of new alveolar septa and by studying the alveolar capillary network in three-dimensional (3-D) visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. We observed that new septa are formed at least until young adulthood (rats, days 4– 60) and that roughly half of the new septa are lifted off of mature septa containing single-layered capillary networks. At the basis of newly forming septa, we detected a local duplication of the capillary network. We conclude that new alveoli may be formed in principle at any time and at any location inside the lung parenchyma and that lung development continues into young adulthood. We define two phases during developmental alveolarization. Phase one ( days 4– 21), lifting off of new septa from immature preexisting septa, and phase two ( day 14 through young adulthood), formation of septa from mature preexisting septa. Clinically, our results ask for precautions using drugs influencing structural lung development during both phases of alveolarization.