De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser–Winter Syndrome

Actin molecules are fundamental for embryonic structural and functional differentiation; γ-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser–Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, ACTB (β-actin) or ACTG1 (γ-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness. Both ACTG1-related non-syndromic A20/A26 deafness and B-WS diagnoses are characterized by hypervariable penetrance in phenotype. Here, we identify a 28th patient worldwide carrying a mutated γ-actin ACTG1 allele, with mildly manifested cerebrofrontofacial B-WS traits, hypervariable penetrance of developmental traits and sensorineural hearing loss. This patient also displays brachycephaly and a complete absence of speech faculty, previously unreported for ACTG1-related B-WS or DFNA20/26 deafness, representing phenotypic expansion. The patient’s exome sequence analyses (ES) confirms a de novo ACTG1 variant previously unlinked to the pathology. Additional microarray analysis uncover no further mutational basis for dual molecular diagnosis in our patient. We conclude that γ-actin c.542C > T, p.Ala181Val is a dominant pathogenic variant, associated with mildly manifested facial and cerebral traits typical of B-WS, hypervariable penetrance of developmental traits and sensorineural deafness. We further posit and present argument and evidence suggesting ACTG1-related non-syndromic DFNA20/A26 deafness is a manifestation of undiagnosed ACTG1-related B-WS.

The Relationships between Plant Developmental Traits and Winter Field Survival in Rye (Secale cereale L.)

Overwintering cereals accumulate low temperature tolerance (LTT) during cold acclimation in the autumn. Simultaneously, the plants adjust to the colder season by making developmental changes at the shoot apical meristem. These processes lead to higher winter hardiness in winter rye varieties (Secale cereale L.) adapted to Northern latitudes as compared to other cereal crops. To dissect the winter-hardiness trait in rye, a panel of 96 genotypes of different origins and growth habits was assessed for winter field survival (WFS), LTT, and six developmental traits. Best Linear Unbiased Estimates for WFS determined from five field trials correlated strongly with LTT (r = 0.90, p < 0.001); thus, cold acclimation efficiency was the major contributor to WFS. WFS also correlated strongly (p < 0.001) with final leaf number (r = 0.80), prostrate growth habit (r = 0.61), plant height (r = 0.34), but showed weaker associations with top internode length (r = 0.30, p < 0.01) and days to anthesis (r = 0.25, p < 0.05). The heritability estimates (h2) for WFS-associated traits ranged from 0.45 (prostrate growth habit) to 0.81 (final leaf number) and were overall higher than for WFS (h2 = 0.48). All developmental traits associated with WFS and LTT are postulated to be regulated by phytohormone levels at shoot apical meristem.

Developmental Traits of Impulse Control Behavior in School Children under Controlled Attention, Motor Function, and Perception

This research surveyed the characteristics of the developmental traits of impulse control behavior in children through parent-report questionnaires. After matching for gender and attention behavior, as well as controlling for variables (motor and perception) which might confound impulse control, 710 participants (355 girls and 355 boys; grade, 1–5; age, 7–12 years) were recruited from a database of 1763 children. Results demonstrated that there was a significant difference between grade 1 and grade 5 in impulse control. Conversely, no significant differences were found when comparing other grades. The present findings indicate that a striking development of impulse control occurs from grade 4 to 5. Moreover, the plateau of impulse control development from grade 1 to 4 implies that a long transition period is needed to prepare children to develop future impulse control. In conclusion, the age-dependent maturation associated with stage-wise development is a critical characteristic of impulse control development in school age children. Further discussions are made regarding this characteristic, such as from the perspective of frontal lobe development.

Evolving the capacity for socially guided vocal learning in songbirds: a preliminary study

Socially guided vocal learning, the ability to use contingent reactions from social partners to guide immature vocalizations to more mature forms, is thought to be a rare ability known to be used only by humans, marmosets and two unrelated songbird species (brown-headed cowbirds and zebra finches). However, this learning strategy has never been investigated in the vast majority of species that are known to modify their vocalizations over development. We propose a novel, preliminary evolutionary modelling approach that uses ecological, reproductive and developmental traits to predict which species may incorporate social influences as part of their vocal learning system. We demonstrate our model using data from 28 passerines. We found three highly predictive traits: temporal overlap between sensory (memorization) and sensorimotor (practice) phases of song learning, song used for mate attraction, and social gregariousness outside the breeding season. Species with these traits were distributed throughout the clade, suggesting that a trait-based approach may yield new insights into the evolution of learning strategies that cannot be gleaned from phylogenetic relatedness alone. Our model suggests several previously uninvestigated and unexpected species as likely socially guided vocal learners and offers new insight into the evolution and development of vocal learning. This article is part of the theme issue ‘Vocal learning in animals and humans’.

Non-additive QTL mapping of lactation traits in 124,000 sequence-imputed cattle reveals novel recessive loci

Deleterious recessive conditions have primarily been studied in a Mendelian disease context. Recently, several large effect, deleterious recessive mutations were discovered via non-additive GWAS of quantitative growth and developmental traits in cattle. This showed quantitative traits can be used as proxies of genetic disorders if they are indicative of whole animal health status and susceptible to underlying genetic conditions. Lactation traits might also reflect genetic disorders in cattle, given the increased energy demands of lactation and the substantial stresses imposed on the animal. Here, we report a screen of over 124,000 cows for recessive effects based on lactation traits. We discovered novel loci associated with five large recessive impacts on milk yield traits represented by missense variants (DOCK8, IL4R, KIAA0556, and SLC25A4) or premature stop variants (ITGAL, LRCH4, and RBM34) as candidate causal mutations. On milk composition traits, we identified several small effect dominance contributions to previously reported additive QTL. In contrasting analyses of milk yield and milk composition phenotypes, we note differing genetic architectures. Milk yield phenotypes presented lower heritabilities and fewer additive QTL, but higher non-additive genetic variance and a higher proportion of loci exhibiting dominance compared to milk composition phenotypes. Large-effect recessive QTL are segregating at surprisingly high frequencies in cattle. We speculate that the differences in genetic architecture between milk yield and milk composition phenotypes derive from underlying dissimilarities in the cellular and molecular representation of these traits. Lactation yields may act as a better proxy than milk composition traits for a wide range of underlying biological disorders affecting animal fitness

Genome Size Dynamics in Marine Ribbon Worms (Nemertea, Spiralia)

Nemertea is a phylum consisting of 1300 mostly marine species. Nemertea is distinguished by an eversible muscular proboscis, and most of the species are venomous. Genomic resources for this phylum are scarce despite their value in understanding biodiversity. Here, we present genome size estimates of Nemertea based on flow cytometry and their relationship to different morphological and developmental traits. Ancestral genome size estimations were done across the nemertean phylogeny. The results increase the available genome size estimates for Nemertea three-fold. Our analyses show that Nemertea has a narrow genome size range (0.43–3.89 pg) compared to other phyla in Lophotrochozoa. A relationship between genome size and evolutionary rate, developmental modes, and habitat was found. Trait analyses show that the highest evolutionary rate of genome size is found in upper intertidal, viviparous species with direct development. Despite previous findings, body size in nemerteans was not correlated with genome size. A relatively small genome (1.18 pg) is assumed for the most recent common ancestor of all extant nemerteans. The results provide an important basis for future studies in nemertean genomics, which will be instrumental to understanding the evolution of this enigmatic and often neglected phylum.

On heterosis, inbreeding depression and general combining ability in annual caraway (Carum carvi)

Caraway (Carum carvi) is a medicinal and aromatic plant of the Apiaceae family with a long history of cultivation. To this day, improvements in yield and essential oil content are desirable. In the past, line breeding was used to increase essential oil content with the final intention of combining inbred lines to a synthetic variety by outcrossing. Outcrossing should overcome inbreeding depression and exploit heterosis vice versa. In this study, we wanted to detect whether and to what extent heterosis can be exploited in caraway. In a randomized complete block design with two years of growing and four repetitions per year and genotype, we compared 18 inbred lines with 18 corresponding F1 populations produced in a polycross. In addition to yield, we estimated the beginning of flowering, the end of flowering, maturity, height, thousand-grain weight, stalk attachment rate, shattering rate and essential oil content. Linear mixed models were used to compute variance components, heritability and best linear unbiased estimates. As major result, we detected the existence of better parent heterosis in caraway. To summarize, outcrossing led to a significant increase in yield, thousand-grain weight and height and to an earlier beginning of flowering, end of flowering and maturity. In two-year data, no effect of outcrossing on the essential oil content was observed, but single year data revealed slight effects. We found strong negative correlations between developmental traits and yield. Hence, selection of early developing genotypes seems highly recommendable. Results make us confident that improved annual varieties can be introduced soon.

Transgenerational Effects of Parental Diet on Offspring Development and Disease Resistance in Flies

The environmental conditions experienced by parents influence next generations, with the parental nutritional status playing an important role in shaping offspring phenotypes. Our understanding of transgenerational effects of parental diet on offspring pathogen resistance is, however, poorly documented. We manipulated the quality of parental diet (i.e., mother, father, or both) and measured effects on offspring development and survival after an immune challenge by septic infection. We used Bactrocera tryoni as host model infected with the pathogenic bacterium, Serratia marcescens. Our results showed no significant effect of maternal, or paternal, diet on offspring resistance. Interestingly, when the diet of both parents was manipulated, sons from parents fed either carbohydrate- or protein-biased diets had higher survival upon pathogen infection than sons from parents fed balanced diets. The quality of the parental diet had no effect on offspring developmental traits with the exception of egg hatching percentage which decreased when mothers were fed a protein-biased diet. Our results emphasised the complexity of nutritional transgenerational effects on offspring pathogen resistance and development.

ERK1/2 is an ancestral organising signal in spiral cleavage

Embryonic organisers are signalling centres that instruct the establishment of body plans during animal embryogenesis, thus underpinning animal morphological diversity. In spiral cleavage - a stereotypic developmental programme ancestral to 14, nearly half, of the animal phyla (e.g., molluscs, annelids and flatworms), a cell known as the D-quadrant organiser defines cell fates and the body axes. ERK1/2 specifies the embryonic organiser in molluscs, yet how this signalling cascade exerts organising activity and whether this role is conserved in other spiral cleaving groups is unclear. Here, we demonstrate that ERK1/2 promotes the specification and inductive activity of the D-quadrant organiser in Owenia fusiformis, an early-branching annelid exhibiting ancestral developmental traits. In this species, active di-phosphorylated ERK1/2 mediated by FGF receptor activity localises to the 4d micromere, establishing the bilateral symmetry and specifying the hindgut and trunk mesodermal progenitor. Accordingly, impairing FGFR and ERK1/2 activity, as well as cell communication results in embryos developing anteroventrally radialised. Differential transcriptomic profiling shows the ParaHox cdx and the Notch ligand delta as FGFR/ERK1/2 downstream targets in 4d, further revealing that 4d specification instructs the expression of mesodermal and posterodorsal genes in neighbouring cells, putatively via the Notch pathway. The instructing role of ERK1/2 in the D-quadrant organiser is thus shared between O. fusiformis and molluscs, representing an ancestral trait of spiral cleavage. Altogether, our study begins to dissect the gene network promoting axial patterning and posterior growth in spiral cleavage, revealing extensive mechanistic diversification in body plan specification despite overall conservation of cleavage patterns in Spiralia.

Thyroid hormones regulate the formation and environmental plasticity of white bars in clownfishes

Determining how plasticity of developmental traits responds to environmental conditions is a challenge that must combine evolutionary sciences, ecology, and developmental biology. During metamorphosis, fish alter their morphology and color pattern according to environmental cues. We observed that juvenile clownfish (Amphiprion percula) modulate the developmental timing of their adult white bar formation during metamorphosis depending on the sea anemone species in which they are recruited. We observed an earlier formation of white bars when clownfish developed with Stichodactyla gigantea (Sg) than with Heteractis magnifica (Hm). As these bars, composed of iridophores, form during metamorphosis, we hypothesized that timing of their development may be thyroid hormone (TH) dependent. We treated clownfish larvae with TH and found that white bars developed earlier than in control fish. We further observed higher TH levels, associated with rapid white bar formation, in juveniles recruited in Sg than in Hm, explaining the faster white bar formation. Transcriptomic analysis of Sg recruits revealed higher expression of duox, a dual oxidase implicated in TH production as compared to Hm recruits. Finally, we showed that duox is an essential regulator of iridophore pattern timing in zebrafish. Taken together, our results suggest that TH controls the timing of adult color pattern formation and that shifts in duox expression and TH levels are associated with ecological differences resulting in divergent ontogenetic trajectories in color pattern development.