scholarly journals An irregular hourglass pattern describes the tempo of phenotypic development in placental mammal evolution

2020 ◽  
Vol 16 (5) ◽  
pp. 20200087
Author(s):  
Gerardo A. Cordero ◽  
Marcelo R. Sánchez-Villagra ◽  
Ingmar Werneburg

Organismal development is defined by progressive transformations that ultimately give rise to distinct tissues and organs. Thus, temporal shifts in ontogeny often reflect key phenotypic differences in phylogeny. Classical theory predicts that interspecific morphological divergence originates towards the end of embryonic or fetal life stages, i.e. the early conservation model. By contrast, the hourglass model predicts interspecific variation early and late in prenatal ontogeny, though with a phylogenetically similar mid-developmental period. This phylotypic period, however, remains challenging to define within large clades such as mammals. Thus, molecular and morphological tests on a mammalian hourglass have not been entirely congruent. Here, we report an hourglass-like pattern for mammalian developmental evolution. By comparing published data on the timing of 74 homologous characters across 51 placental species, we demonstrated that variation in the timing of development decreased late in embryogenesis––when organ formation is highly active. Evolutionary rates of characters related to this timeframe were lowest, coinciding with a phylotypic period that persisted well beyond the pharyngula ‘stage’. The trajectory culminated with elevated variation in a handful of fetal and perinatal characters, yielding an irregular hourglass pattern. Our study invites further quantification of ontogeny across diverse amniotes and thus challenges current ideas on the universality of developmental patterns.

2019 ◽  
Vol 36 (7) ◽  
pp. 1373-1383 ◽  
Author(s):  
Longjun Wu ◽  
Kailey E Ferger ◽  
J David Lambert

Abstract It has been proposed that animals have a pattern of developmental evolution resembling an hourglass because the most conserved development stage—often called the phylotypic stage—is always in midembryonic development. Although the topic has been debated for decades, recent studies using molecular data such as RNA-seq gene expression data sets have largely supported the existence of periods of relative evolutionary conservation in middevelopment, consistent with the phylotypic stage and the hourglass concepts. However, so far this approach has only been applied to a limited number of taxa across the tree of life. Here, using established phylotranscriptomic approaches, we found a surprising reverse hourglass pattern in two molluscs and a polychaete annelid, representatives of the Spiralia, an understudied group that contains a large fraction of metazoan body plan diversity. These results suggest that spiralians have a divergent midembryonic stage, with more conserved early and late development, which is the inverse of the pattern seen in almost all other organisms where these phylotranscriptomic approaches have been reported. We discuss our findings in light of proposed reasons for the phylotypic stage and hourglass model in other systems.


2020 ◽  
Vol 4 (6) ◽  
pp. 1131-1144 ◽  
Author(s):  
Anna L. Brown ◽  
Peer Arts ◽  
Catherine L. Carmichael ◽  
Milena Babic ◽  
Julia Dobbins ◽  
...  

Abstract First reported in 1999, germline runt-related transcription factor 1 (RUNX1) mutations are a well-established cause of familial platelet disorder with predisposition to myeloid malignancy (FPD-MM). We present the clinical phenotypes and genetic mutations detected in 10 novel RUNX1-mutated FPD-MM families. Genomic analyses on these families detected 2 partial gene deletions, 3 novel mutations, and 5 recurrent mutations as the germline RUNX1 alterations leading to FPD-MM. Combining genomic data from the families reported herein with aggregated published data sets resulted in 130 germline RUNX1 families, which allowed us to investigate whether specific germline mutation characteristics (type, location) could explain the large phenotypic heterogeneity between patients with familial platelet disorder and different HMs. Comparing the somatic mutational signatures between the available familial (n = 35) and published sporadic (n = 137) RUNX1-mutated AML patients showed enrichment for somatic mutations affecting the second RUNX1 allele and GATA2. Conversely, we observed a decreased number of somatic mutations affecting NRAS, SRSF2, and DNMT3A and the collective genes associated with CHIP and epigenetic regulation. This is the largest aggregation and analysis of germline RUNX1 mutations performed to date, providing a unique opportunity to examine the factors underlying phenotypic differences and disease progression from FPD to MM.


2021 ◽  
Vol 27 (02) ◽  
pp. 101-110
Author(s):  
I.-K. Penner ◽  
H. Schreiber

Zusammenfassung Obgleich sich die Zahl und die Wirkansätze der verfügbaren Immuntherapien zur Behandlung der MS in den letzten zehn Jahren deutlich vergrößert haben, ist die Datenlage zur Wirkung der verschiedenen Behandlungsformen auf Fatigue nach wie vor lückenhaft und kaum durch kontrollierte Daten belegt. Aus den in dieser Arbeit referierten Studien kann vorläufig geschlossen werden, dass von Glatirameracetat und Natalizumab am ehesten positive Auswirkungen auf das Fatigueempfinden von MS Patienten zu erwarten sind. Bei Interferonen bietet die Datenlage keine einheitliche Orientierung. Die klinische Erfahrung lehrt jedoch, dass man immer damit rechnen muss, dass eine Interferontherapie bei einzelnen Patienten zu einer Zunahme der Fatigue führt. Ein Absetzen von Interferon und ein Wechsel auf Glatirameracetat oder eines der Oralpräparate (horizontal switch) kann deshalb unter dem Aspekt der Fatigue bei Krankheitsstabilität durchaus sinnvoll sein. Die modernen Antikörpertherapien scheinen hinsichtlich einer Fatigueauslösung oder -verschlechterung eher unkritisch zu sein. Kurzfristige Schwankungen der Fatigue können aber vorkommen. Vielversprechend sehen derzeit die Daten zu Ponesimod aus, wobei es hier zu beachten gilt, dass das Messinstrument für Fatigue neu entwickelt wurde und es hierzu keinerlei Vergleichsdaten mit anderen Präparaten – abgesehen vom aktiven Komparator Teriflunomid aus der Zulassungsstudie – gibt. Hier besteht demnach wissenschaftlicher Handlungsbedarf, um zu sicherzustellen, dass es sich um eine »echte Überlegenheit« von Ponesimod in puncto Fatigue gegenüber anderen Therapien handelt. Schlüsselwörter: Multiple Sklerose, Fatigue, Therapie der Fatigue, Immuntherapien, milde bis moderate Verlaufsformen der MS, aktive bis hochaktive Verlaufsformen der MS Abstract Although the number and the mode of action of the immunotherapies available for the treatment of MS have increased significantly in the last ten years, evidence for the effect of the various forms of treatment on fatigue is still incomplete and hardly supported by controlled data. From the studies reported in this paper, it can be tentavely concluded that glatiramer acetate and natalizumab are most likely to have positive effects on the perception of fatigue in MS patients. In the case of interferons, published data do not offer a uniform orientation. However, clinical experience shows that it must always be expected that interferon therapy will lead to an increase in fatigue in individual patients. Discontinuing interferon and switching to glatiramer acetate or one of the oral drugs (horizontal switch) can therefore make sense in terms of fatigue and disease stability. Modern antibody therapies seem to be rather uncritical in terms of triggering or worsening fatigue. However, short-term fluctuations in fatigue can occur. The data on ponesimod currently look promising, although it should be noted that the measuring instrument for fatigue was newly developed and that there are no comparative data with other disease modifying therapies – apart from the active comparator teriflunomide from the registration study. There is therefore a need for scientific action here to ensure that ponesimod has a »real superiority« in terms of fatigue compared to other therapies. Keywords: multiple sclerosis, fatigue, management of fatigue, immunotherapies, mild to moderate MS, active to highly active MS


2017 ◽  
Author(s):  
Jialin Liu ◽  
Marc Robinson-Rechavi

AbstractDevelopmental constraints on genome evolution have been suggested to follow either an early conservation model or an “hourglass” model. Both models agree that late development strongly diverges between species, but debate on which developmental period is the most conserved. Here, based on a modified “Transcriptome Age Index” approach, i.e. weighting trait measures by expression level, we analyzed the constraints acting on three evolutionary traits of protein coding genes (strength of purifying selection on protein sequences, phyletic age, and duplicability) in four species: nematode worm Caenorhabditis elegans, fly Drosophila melanogaster, zebrafish Danio rerio, and mouse Mus musculus. In general, we found that both models can be supported by different genomic properties. Sequence evolution follows an hourglass model, but the evolution of phyletic age and of duplicability follow an early conservation model. Further analyses indicate that stronger purifying selection on sequences in the middle development are driven by temporal pleiotropy of these genes. In addition, we report evidence that expression in late development is enriched with retrogenes, which usually lack efficient regulatory elements. This implies that expression in late development could facilitate transcription of new genes, and provide opportunities for acquisition of function. Finally, in C. elegans, we suggest that dosage imbalance could be one of the main factors that cause depleted expression of high duplicability genes in early development.


2009 ◽  
Vol 76 (3) ◽  
pp. 631-639 ◽  
Author(s):  
Karel Šimek ◽  
Vojtěch Kasalický ◽  
Jan Jezbera ◽  
Jitka Jezberová ◽  
Josef Hejzlar ◽  
...  

ABSTRACT The distribution of the phylogenetically narrow R-BT065 cluster (Betaproteobacteria) in 102 freshwater lakes, reservoirs, and various ponds located in central Europe (a total of 122 samples) was examined by using a cluster-specific fluorescence in situ hybridization probe. These habitats differ markedly in pH, conductivity, trophic status, surface area, altitude, bedrock type, and other limnological characteristics. Despite the broad ecological diversity of the habitats investigated, the cluster was detected in 96.7% of the systems, and its occurrence was not restricted to a certain habitat type. However, the relative proportions of the cluster in the total bacterioplankton were significantly lower in humic and acidified lakes than in pH-neutral or alkaline habitats. On average, the cluster accounted for 9.4% of the total bacterioplankton (range, 0 to 29%). The relative abundance and absolute abundance of these bacteria were significantly and positively related to higher pH, conductivity, and the proportion of low-molecular-weight compounds in dissolved organic carbon (DOC) and negatively related to the total DOC and dissolved aromatic carbon contents. Together, these parameters explained 55.3% of the variability in the occurrence of the cluster. Surprisingly, no clear relationship of the R-BT065 bacteria to factors indicating the trophic status of habitats (i.e., different forms of phosphorus and chlorophyll a content) was found. Based on our results and previously published data, we concluded that the R-BT065 cluster represents a ubiquitous, highly active segment of bacterioplankton in nonacidic lakes and ponds and that alga-derived substrates likely form the main pool of substrates responsible for its high growth potential and broad distribution in freshwater habitats.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Karl R Wotton ◽  
Eva Jiménez-Guri ◽  
Anton Crombach ◽  
Hilde Janssens ◽  
Anna Alcaine-Colet ◽  
...  

The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring ‘quantitative system drift’. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.


Author(s):  
W. Kuenzig ◽  
M. Boublik ◽  
J.J. Kamm ◽  
J.J. Burns

Unlike a variety of other animal species, such as the rabbit, mouse or rat, the guinea pig has a relatively long gestation period and is a more fully developed animal at birth. Kuenzig et al. reported that drug metabolic activity which increases very slowly during fetal life, increases rapidly after birth. Hepatocytes of a 3-day old neonate metabolize drugs and reduce cytochrome P-450 at a rate comparable to that observed in the adult animal. Moreover the administration of drugs like phenobarbital to pregnant guinea pigs increases the microsomal mixed function oxidase activity already in the fetus.Drug metabolic activity is, generally, localized within the smooth endoplasmic reticulum (SER) of the hepatocyte.


2020 ◽  
Vol 477 (15) ◽  
pp. 2921-2934
Author(s):  
Rodrigo D. Requião ◽  
Géssica C. Barros ◽  
Tatiana Domitrovic ◽  
Fernando L. Palhano

Protein segments with a high concentration of positively charged amino acid residues are often used in reporter constructs designed to activate ribosomal mRNA/protein decay pathways, such as those involving nonstop mRNA decay (NSD), no-go mRNA decay (NGD) and the ribosome quality control (RQC) complex. It has been proposed that the electrostatic interaction of the positively charged nascent peptide with the negatively charged ribosomal exit tunnel leads to translation arrest. When stalled long enough, the translation process is terminated with the degradation of the transcript and an incomplete protein. Although early experiments made a strong argument for this mechanism, other features associated with positively charged reporters, such as codon bias and mRNA and protein structure, have emerged as potent inducers of ribosome stalling. We carefully reviewed the published data on the protein and mRNA expression of artificial constructs with diverse compositions as assessed in different organisms. We concluded that, although polybasic sequences generally lead to lower translation efficiency, it appears that an aggravating factor, such as a nonoptimal codon composition, is necessary to cause translation termination events.


2004 ◽  
Vol 71 ◽  
pp. 193-202 ◽  
Author(s):  
David R Brown

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. To this end much work has focused on elucidation of the normal function and activity of PrPc. Substantial evidence supports the notion that PrPc is a copper-binding protein. In conversion to the abnormal isoform, this Cu-binding activity is lost. Instead, there are some suggestions that the protein might bind other metals such as Mn or Zn. PrPc functions currently under investigation include the possibility that the protein is involved in signal transduction, cell adhesion, Cu transport and resistance to oxidative stress. Of these possibilities, only a role in Cu transport and its action as an antioxidant take into consideration PrPc's Cu-binding capacity. There are also more published data supporting these two functions. There is strong evidence that during the course of prion disease, there is a loss of function of the prion protein. This manifests as a change in metal balance in the brain and other organs and substantial oxidative damage throughout the brain. Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies.


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