Predicting evolutionary targets and parameters of gene deletion from expression data.

Motivation: Gene deletion is traditionally thought of as a nonadaptive process that removes functional redundancy from genomes, such that it generally receives less attention than duplication in evolutionary turnover studies. Yet, mounting evidence suggests that deletion may promote adaptation via the "less-is-more" evolutionary hypothesis, as it often targets genes harboring unique sequences, expression profiles, and molecular functions. Hence, predicting the relative prevalence of redundant and unique functions among genes targeted by deletion, as well as the parameters underlying their evolution, can shed light on the role of gene deletion in adaptation. Results: Here, we present CLOUDe, a suite of machine learning methods for predicting evolutionary targets of gene deletion events from expression data. Specifically, CLOUDe models expression evolution as an Ornstein-Uhlenbeck process, and uses multi-layer neural network, extreme gradient boosting, random forest, and support vector machine architectures to predict whether deleted genes are "redundant" or "unique", as well as several parameters underlying their evolution. We show that CLOUDe boasts high power and accuracy in differentiating between classes, and high accuracy and precision in estimating evolutionary parameters, with optimal performance achieved by its neural network architecture. Application of CLOUDe to empirical data from Drosophila suggests that deletion primarily targets genes with unique functions, with further analysis showing these functions to be enriched for protein deubiquitination. Thus, CLOUDe represents a key advance in learning about the role of gene deletion in functional evolution and adaptation. Availability and implementation: CLOUDe is freely available on GitHub (https://github.com/anddssan/CLOUDe).

Robust phylogenetic regression.

Modern comparative biology owes much to phylogenetic regression. At its conception, this technique sparked a revolution that armed biologists with phylogenetic comparative methods (PCMs) for disentangling evolutionary correlations from those arising from hierarchical phylogenetic relationships. Over the past few decades, the phylogenetic regression framework has become a paradigm of modern comparative biology that has been widely embraced as a remedy for shared ancestry. However, recent evidence has sown doubt over the efficacy of phylogenetic regression, and PCMs more generally, with the suggestion that many of these methods fail to provide an adequate defense against unreplicated evolution-the primary justification for using them in the first place. Importantly, some of the most compelling examples of biological innovation in nature result from abrupt lineage-specific evolutionary shifts, which current regression models are largely ill-equipped to deal with. Here we explore a solution to this problem by applying robust linear regression to comparative trait data. We formally introduce robust phylogenetic regression to the PCM toolkit with linear estimators that are less sensitive to model violations than the standard least-squares estimator, while still retaining high power to detect true trait associations. Our analyses also highlight an ingenuity of the original algorithm for phylogenetic regression based on independent contrasts, whereby robust estimators are particularly effective. Collectively, we find that robust estimators hold promise for improving tests of trait associations and offer a path forward in scenarios where classical approaches may fail. Our study joins recent arguments for increased vigilance against unreplicated evolution and a better understanding of evolutionary model performance in challenging-yet biologically important-settings.

Predicting gene expression divergence between single-copy orthologs in two species.

Predicting gene expression divergence is integral to understanding the emergence of new biological functions and associated traits. Whereas several sophisticated methods have been developed for this task, their applications are either limited to duplicate genes or require expression data from more than two species. Thus, here we present PiXi, the first machine learning framework for predicting gene expression divergence between single-copy orthologs in two species. PiXi models gene expression evolution as an Ornstein-Uhlenbeck process, and overlays this model with multi-layer neural network, random forest, and support vector machine architectures for making predictions. It outputs the predicted class "conserved" or "diverged" for each pair of orthologs, as well as their predicted expression optima in the two species. We show that PiXi has high power and accuracy in predicting gene expression divergence between single-copy orthologs, as well as high accuracy and precision in estimating their expression optima in the two species, across a wide range of evolutionary scenarios, with the globally best performance achieved by a multi-layer neural network. Moreover, application of our best performing PiXi predictor to empirical gene expression data from single-copy orthologs residing at different loci in two species of Drosophila reveals that approximately 23% underwent expression divergence after positional relocation. Further analysis shows that several of these "diverged" genes are involved in the electron transport chain of the mitochondrial membrane, suggesting that new chromatin environments may impact energy production in Drosophila. Thus, by providing a toolkit for predicting gene expression divergence between single-copy orthologs in two species, PiXi can shed light on the origins of novel phenotypes across diverse biological processes and study systems.

Models for the retention of duplicate genes and their biological underpinnings.

Gene content in genomes changes through several different processes, with gene duplication being an important contributor to such changes. Gene duplication occurs over a range of scales from individual genes to whole genomes, and the dynamics of this process can be context dependent. Still, there are rules by which genes are retained or lost from genomes after duplication, and probabilistic modeling has enabled characterization of these rules, including their context-dependence. Here, we describe the biology and corresponding mathematical models that are used to understand duplicate gene retention and its contribution to the set of biochemical functions encoded in a genome.

Epistasis-Driven Evolution of the SARS-CoV-2 Secondary Structure.

Epistasis is an evolutionary phenomenon whereby the fitness effect of a mutation depends on the genetic background in which it arises. A key source of epistasis in an RNA molecule is its secondary structure, which contains functionally important topological motifs held together by hydrogen bonds between Watson-Crick (WC) base pairs. Here we study epistasis in the secondary structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by examining properties of derived alleles arising from substitution mutations at ancestral WC base-paired and unpaired (UP) sites in 15 conserved topological motifs across the genome. We uncover fewer derived alleles and lower derived allele frequencies at WC than at UP sites, supporting the hypothesis that modifications to the secondary structure are often deleterious. At WC sites, we also find lower derived allele frequencies for mutations that abolish base pairing than for those that yield G·U "wobbles," illustrating that weak base pairing can partially preserve the integrity of the secondary structure. Last, we show that WC sites under the strongest epistatic constraint reside in a three-stemmed pseudoknot motif that plays an essential role in programmed ribosomal frameshifting, whereas those under the weakest epistatic constraint are located in 3' UTR motifs that regulate viral replication and pathogenicity. Our findings demonstrate the importance of epistasis in the evolution of the SARS-CoV-2 secondary structure, as well as highlight putative structural and functional targets of different forms of natural selection.

Assistência de enfermagem ao paciente politraumatizado / Nursing assistance to the polytraumated patient / Asistencia de enfermería al paciente politraumado

Introdução: Politrauma é uma das maiores causas de mortalidade em pessoas adolescentes e adultos jovens, podendo levar a consequências e danos permanentes e gerar mudanças significativas na rotina pessoal, quando não ocorre o óbito. O cuidado de enfermagem é fundamental e importante a esses pacientes, a ser realizado por meio de conhecimentos específicos, visando auxiliar a qualidade assistencial. Objetivo: Descrever e destacar a importância da assistência de enfermagem a pacientes politraumatizados. Material e Método: Estudo de revisão de literatura, descritiva com abordagem qualitativa, sendo a coleta de dados realizada na base de dados BVS. Resultados: Os 8 artigos selecionados foram submetidos a Análise Temática de Conteúdo, sendo trabalhadas duas categorias temáticas: Assistência de enfermagem ao paciente politraumatizado e, Processo de enfermagem na assistência a politraumatizados. Identificou-se que o cuidado assistencial de enfermagem a esses pacientes é essencial, devendo ser prestado de maneira ágil, eficaz e segura, exigindo, portanto, treinamento e capacitação prévia do enfermeiro para identificar junto a equipe, lesões existentes, garantir a estabilização no menor tempo possível e manter a sobrevida, durante o atendimento pré-hospitalar e posteriormente no ambiente hospitalar. O processo de enfermagem inclui avaliação primária no atendimento, seguida pela secundária e as fases do processo de enfermagem devem ser asseguradas contemplando os objetivos propostos, durante todo o tratamento. Conclusão: A assistência a pacientes politraumatizados deve ser desenvolvida por meio de protocolos específicos, ordenados sequencialmente, buscando-se como medida, determinar a responsividade do indivíduo. A temática é significativa, complexa e requer novos estudos e atualizações. (AU)

Introduction: Polytrauma is one of the major causes of mortality in adolescents and young adults, and can lead to permanent consequences and damage and generate significant changes in personal routine, when death does not occur. Nursing care is fundamental and important for these patients, to be carried out through specific knowledge, aiming to help the quality of care. Objective: To describe and highlight the importance of nursing care for polytraumatized patients. Material and Method: A descriptive literature review study with a qualitative approach, with data collection carried out in the VHL database. Results: The 8 selected articles were submitted to Thematic Content Analysis, with two thematic categories being worked on: Nursing care for the polytraumatized patient and, Nursing process in the care of polytraumatized patients. It was identified that nursing care care for these patients is essential, and must be provided in an agile, effective and safe way, therefore requiring training and prior qualification of nurses to identify existing injuries with the team, ensure stabilization in the smallest possible time and maintain survival, during pre-hospital care and later in the hospital environment. The nursing process includes primary assessment in care, followed by secondary and the phases of the nursing process must be ensured, considering the proposed objectives, throughout the treatment. Conclusion: Assistance to polytraumatized patients must be developed through specific protocols, ordered sequentially, seeking as a measure, to determine the individual's responsiveness. The theme is significant, complex and requires further studies and updates.(AU)

Introducción: El politraumatismo es una de las principales causas de mortalidad en adolescentes y adultos jóvenes, pudiendo tener secuelas y daños permanentes y generar cambios significativos en la rutina personal, cuando la muerte no se presenta. El cuidado de enfermería es fundamental e importante para estos pacientes, siendo realizado a través de conocimientos específicos, con el objetivo de ayudar y mejorar la calidad del cuidado. Objetivo: Describir y resaltar la importancia del cuidado de enfermería al paciente politraumatizado. Material y Método: Estudio descriptivo de revisión bibliográfica con abordaje cualitativo, con recolección de datos realizada en la base de datos de la BVS. Resultados: Los 8 artículos seleccionados fueron sometidos al Análisis de Contenido Temático, siendo trabajadas dos categorías temáticas: Atención de Enfermería al politraumatizado y Proceso de Enfermería en el cuidado al politraumatizado. Se identificó que el cuidado de enfermería a estos pacientes es fundamental, y debe ser brindado de forma ágil, eficaz y segura, por lo que se requiere de capacitación y calificación previa de los enfermeros para identificar las lesiones existentes con el equipo, garantizar la estabilización en los más pequeños en tanto posible...(AU)

No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals.

Nested protein-coding genes accumulated throughout metazoan evolution, with early analyses of human and Drosophila microarray data indicating that this phenomenon was simply due to the presence of large introns. However, a recent study employing RNA-seq data uncovered evidence of transcriptional interference driving rapid expression divergence between Drosophila nested genes, illustrating that accurate expression estimation of overlapping genes can enhance detection of their relationships. Hence, here I apply an analogous approach to strand-specific RNA-seq data from human and mouse to revisit the role of transcriptional interference in the evolution of mammalian nested genes. A genomic survey reveals that whereas mammalian nested genes indeed accrued over evolutionary time, they are retained at lower frequencies than in Drosophila. Though several properties of mammalian nested genes align with observations in Drosophila and with expectations under transcriptional interference, contrary to both, their expression divergence is not statistically different from that between unnested genes, and also does not increase after nesting. Together, these results support the hypothesis that lower selection efficiencies limit rates of gene expression evolution in mammals, leading to their reliance on immediate eradication of deleterious nested genes to avoid transcriptional interference.

BLAST from the Past: Impacts of Evolving Approaches on Studies of Evolution by Gene Duplication.

In 1970, Susumu Ohno hypothesized that gene duplication was a major reservoir of adaptive innovation. However, it was not until over two decades later that DNA sequencing studies uncovered the ubiquity of gene duplication across all domains of life, highlighting its global importance in the evolution of phenotypic complexity and species diversification. Today, it seems that there are no limits to the study of evolution by gene duplication, as it has rapidly coevolved with numerous experimental and computational advances in genomics. In this perspective, we examine word stem usage in PubMed abstracts to infer how evolving discoveries and technologies have shaped the landscape of studying evolution by gene duplication, leading to a more refined understanding of its role in the emergence of novel phenotypes.

Impasses na aprendizagem e inibição intelectual / Impasses dans l'apprentissage et inhibition intellectuelle / Impasses in learning and intellectual inhibition

O presente artigo descreve os resultados de uma pesquisa-intervenção de orientação psicanalítica por meio do relato de um estudo de caso de um aluno do ensino fundamental de uma escola pública da rede estadual de ensino da cidade de Itabira-MG. O estudante enfrenta vários entraves na aprendizagem que dificultam sua alfabetização e seu processo de letramento. O caso visa demonstrar a contribuição de um dos instrumentos utilizados nessa pesquisa que é o diagnóstico clínico-pedagógico (DCP), cuja intervenção realiza a leitura daquilo que o menino ensinaao educador sobre sua subjetividade e a forma como suas particularidades podem interferir na relação com o saber. Os resultados obtidos na pesquisa permitiram perceber como a angústia de castração, os temores infantis e as fobias podem se constituir no fenômeno da inibição intelectual e comprometer toda a trajetória escolar do aluno.

Impasses dans l'apprentissage et inhibition intellectuelle: Cet article décrit les résultats d'une recherche-intervention psychanalytique à travers le rapport d'une étude de cas d'un élève dans la primaire d'une école publique de la ville d'Itabira-MG. L'élève fait face à plusieurs obstacles dans l'apprentissage qui entravent son processus d'alphabétisation. L'étude de cas vise à démontrer l'apport d'un méthode d'investigation utilisé dans cette recherche, qui est le diagnostic clinico-pédagogique (DCP), dont l'idée est d'apprendre avec le garçon ce qu'il enseigne à l'éducateur sur sadifficulté et compris les éléments de subjectivité que sont en tant d' interférer dans sa relation avec l'apprentissage. Les résultats obtenus dans la recherche ont permis de percevoir comment l'angoisse de castration, les peurs infantiles et les phobies peuvent être à l'origine de l'inhibition intellectuelle, en compromettant toute la trajectoire scolaire de l'élève.

mpasses in learning and intellectual inhibition: This article describes the results of a psychoanalytic-oriented research-intervention through the report of a case study of an elementary school student at a public school in the state school in the city of Itabira-MG. The student faces several obstacles in learning, which hinder his literacy and his literacy process. The aim is to demonstrate the contribution of one of the instruments used in this research, which is the clinical-pedagogical diagnosis (CDP). It's intervention reads what the boy teaches the educator about his subjectivity and how his particularities can interfere in the relationship with knowledge. The results obtained by the research allowed us to perceive how castration anxiety, infantile fears and phobias can constitute the phenomenon of intellectual inhibition and compromise the student's entire school journey.

Psicologia Pedagógica e desenvolvimento das funções psicológicas complexas: uma proposta entre tradição e renovação educacional / Pedagogical Psychology and development of complex psychological functions: a proposal between tradition and educational renewal

Esse artigo analisa a proposta de psicologia articulada à educação da obra Psychologie Pédagogique. L'enfant. L'adolescent. Le jeune homme (1916/1938a), à luz de um Aviso publicado na Revista do Ensino, em 1930, que indicava esse livro como leitura para professores no contexto de reforma educacional em Minas Gerais. O artigo investiga essas duas fontes, utilizando como referencial a definição de campo cultural da ciência de Feldhay, o conceito de acomodação proposto por Massimi e elaborações de Chartier sobre táticas de leitores, práticas de leitura e escolhas editoriais. O texto é organizado em três tópicos: recomendação de leituras para formação de professores; o valor e o limite do método científico na educação; psicologia pedagógica e funcionamento das funções superiores complexas. A pesquisa evidencia que a leitura de Psychologie Pédagogique foi recomendada por realizar uma acomodação entre a doutrina católica e os saberes pedagógicos modernos, bem como por apresentar uma Psicologia científica capaz de considerar a dimensão espiritual e sobrenatural do ser humano.

This article analyzes the proposal of psychology linked to education in the work Psychologie Pédagogique. L'enfant. L'adolescent. Le jeune homme(1916/1938a), in the light of a Notice published in the Revista do Ensino [Teaching Magazine], in 1930, which recommended the reading of this book to teachers in the context of educational reform in Minas Gerais state. The article investigates these two sources using as reference Feldhay's definition of science cultural field, the concept of accommodation proposed by Massimi and Chartier's elaborations on readers' tactics, reading practices and editorial choices. The text is organized into three topics: recommending readings for teachers' education, the value and limits of the scientific method in education, pedagogical psychology, and the functioning of complex higher functions. The research shows that the reading of Psychologie Pédagogiquewas recommended due to the fact that it establishes a settlement between Catholic doctrine and modern pedagogical knowledge, as well asfor presenting a scientific psychology capable of considering the spiritual and supernatural dimension of the human being.Keywords: History of Psychology; education; Jesuits.

Learning Retention Mechanisms and Evolutionary Parameters of Duplicate Genes from Their Expression Data.

Learning about the roles that duplicate genes play in the origins of novel phenotypes requires an understanding of how their functions evolve. A previous method for achieving this goal, CDROM, employs gene expression distances as proxies for functional divergence and then classifies the evolutionary mechanisms retaining duplicate genes from comparisons of these distances in a decision tree framework. However, CDROM does not account for stochastic shifts in gene expression or leverage advances in contemporary statistical learning for performing classification, nor is it capable of predicting the parameters driving duplicate gene evolution. Thus, here we develop CLOUD, a multi-layer neural network built on a model of gene expression evolution that can both classify duplicate gene retention mechanisms and predict their underlying evolutionary parameters. We show that not only is the CLOUD classifier substantially more powerful and accurate than CDROM, but that it also yields accurate parameter predictions, enabling a better understanding of the specific forces driving the evolution and long-term retention of duplicate genes. Further, application of the CLOUD classifier and predictor to empirical data from Drosophila recapitulates many previous findings about gene duplication in this lineage, showing that new functions often emerge rapidly and asymmetrically in younger duplicate gene copies, and that functional divergence is driven by strong natural selection. Hence, CLOUD represents a major advancement in classifying retention mechanisms and predicting evolutionary parameters of duplicate genes, thereby highlighting the utility of incorporating sophisticated statistical learning techniques to address long-standing questions about evolution after gene duplication.

Population-Specific Genetic and Expression Differentiation in Europeans.

Much of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here, we explore this problem by simultaneously examining population-specific genetic and expression differentiation in four human populations. In particular, we derive a branch-based estimator of population-specific differentiation in four populations, and apply this statistic to single-nucleotide polymorphism and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of genetic and expression differentiation each independently recapitulate the known relationships among these four human populations, highlighting the utility of our statistic for identifying putative targets of population-specific adaptations. Moreover, genes with large copy number variations display elevated levels of population-specific genetic and expression differentiation, consistent with the hypothesis that gene duplication and deletion events are key reservoirs of adaptive variation. Further, many top-scoring genes are well-known targets of adaptation in Europeans, including those involved in lactase persistence and vitamin D absorption, and a handful of novel candidates represent promising avenues for future research. Together, these analyses reveal that our statistic can aid in uncovering genes involved in population-specific genetic and expression differentiation, and that such genes often play important roles in a diversity of adaptive and disease-related phenotypes in humans.

Out of the testis, into the ovary: biased outcomes of gene duplication and deletion in Drosophila.

Gene turnover is a key source of adaptive variation. Yet most evolutionary studies have focused on gene duplication, dismissing gene deletion as a mechanism that simply eradicates redundancy. Here, I use genome-scale sequence and multi-tissue expression data from Drosophila melanogaster and Drosophila pseudoobscura to simultaneously assess the evolutionary outcomes of gene duplication and deletion in Drosophila. I find that gene duplication is more frequent than gene deletion in both species, indicating that it may play a more important role in Drosophila evolution. However, examination of several genic properties reveals that genes likely possess distinct functions after duplication that diverge further before deletion, suggesting that loss of redundancy cannot explain a majority of gene deletion events in Drosophila. Moreover, in addition to providing support for the well-known "out of the testis" origin of young duplicate genes, analyses of gene expression profiles uncover a preferential bias against deletion of old ovary-expressed genes. Therefore, I propose a novel "into the ovary" hypothesis for gene deletion in Drosophila, in which gene deletion may promote adaptation by salvaging genes that contribute to the evolution of female reproductive phenotypes. Under this combined "out of the testis, into the ovary" evolutionary model, gene duplication and deletion work in concert to generate and maintain a balanced repertoire of genes that promote sex-specific adaptation in Drosophila.

Rapid functional divergence after small-scale gene duplication in grasses.

BACKGROUND: Gene duplication has played an important role in the evolution and domestication of flowering plants. Yet little is known about how plant duplicate genes evolve and are retained over long timescales, particularly those arising from small-scale duplication (SSD) rather than whole-genome duplication (WGD) events. RESULTS: We address this question in the Poaceae (grass) family by analyzing gene expression data from nine tissues of Brachypodium distachyon, Oryza sativa japonica (rice), and Sorghum bicolor (sorghum). Consistent with theoretical predictions, expression profiles of most grass genes are conserved after SSD, suggesting that functional conservation is the primary outcome of SSD in grasses. However, we also uncover support for widespread functional divergence, much of which occurs asymmetrically via the process of neofunctionalization. Moreover, neofunctionalization preferentially targets younger (child) duplicate gene copies, is associated with RNA-mediated duplication, and occurs quickly after duplication. Further analysis reveals that functional divergence of SSD-derived genes is positively correlated with both sequence divergence and tissue specificity in all three grass species, and particularly with anther expression in B. distachyon. CONCLUSIONS: Our results suggest that SSD-derived grass genes often undergo rapid functional divergence that may be driven by natural selection on male-specific phenotypes. These observations are consistent with those in several animal species, suggesting that duplicate genes take similar evolutionary trajectories in plants and animals.

Lineage-Specific Expression Divergence in Grasses Is Associated with Male Reproduction, Host-Pathogen Defense, and Domestication.

Poaceae (grasses) is an agriculturally important and widely distributed family of plants with extraordinary phenotypic diversity, much of which was generated under recent lineage-specific evolution. Yet, little is known about the genes and functional modules involved in the lineage-specific divergence of grasses. Here, I address this question on a genome-wide scale by applying a novel branch-based statistic of lineage-specific expression divergence, LED, to RNA-seq data from nine tissues of the wild grass Brachypodium distachyon and its domesticated relatives Oryza sativa japonica (rice) and Sorghum bicolor (sorghum). I find that LED is generally smallest in B. distachyon and largest in O. sativa japonica, which underwent domestication earlier than S. bicolor, supporting the hypothesis that domestication may increase the rate of lineage-specific expression divergence in grasses. Moreover, in all three species, LED is positively correlated with protein-coding sequence divergence and tissue specificity, and negatively correlated with network connectivity. Further analysis reveals that genes with large LED are often primarily expressed in anther, implicating lineage-specific expression divergence in the evolution of male reproductive phenotypes. Gene ontology enrichment analysis also identifies an overrepresentation of terms related to male reproduction in the two domesticated grasses, as well as to those involved in host-pathogen defense in all three species. Last, examinations of genes with the largest LED reveal that their lineage-specific expression divergence may have contributed to antimicrobial functions in B. distachyon, to enhanced adaptation and yield during domestication in O. sativa japonica, and to defense against a widespread and devastating fungal pathogen in S. bicolor. Together, these findings suggest that lineage-specific expression divergence in grasses may increase under domestication and preferentially target rapidly evolving genes involved in male reproduction, host-pathogen defense, and the origin of domesticated phenotypes.

Natural Selection Drives Rapid Functional Evolution of Young Drosophila Duplicate Genes.

Gene duplication is thought to play a major role in phenotypic evolution. Yet the forces involved in the functional divergence of young duplicate genes remain unclear. Here, we use population-genetic inference to elucidate the role of natural selection in the functional evolution of young duplicate genes in Drosophila melanogaster. We find that negative selection acts on young duplicates with ancestral functions, and positive selection on those with novel functions, suggesting that natural selection may determine whether and how young duplicate genes are retained. Moreover, evidence of natural selection is strongest in protein-coding regions and 3' UTRs of young duplicates, indicating that selection may primarily target encoded proteins and regulatory sequences specific to 3' UTRs. Further analysis reveals that natural selection acts immediately after duplication and weakens over time, possibly explaining the observed bias toward the acquisition of new functions by young, rather than old, duplicate gene copies. Last, we find an enrichment of testis-related functions in young duplicates that underwent recent positive selection, but not in young duplicates that did not undergo recent positive selection, or in old duplicates that either did or did not undergo recent positive selection. Thus, our findings reveal that natural selection is a key player in the functional evolution of young duplicate genes, acts rapidly and in a region-specific manner, and may underlie the origin of novel testis-specific phenotypes in Drosophila.

Exercitar as Funções Psíquicas: Ortopedia Mental como Método de Ensino das Classes Especiais (1930)1 / Exercising Psychic Functions: Mental Orthopedics as a Teaching Method for Students with Especial Needs (1930)

RESUMO: a pesquisa apresentada investigou o método de Ortopedia Mental elaborado pela educadora Helena Antipoff, enfocando seus fundamentos teóricos. Utilizamos como fontes os textos da educadora escritos na década de 1930 e compilados em dois volumes da Coletânea das obras escritas de Helena Antipoff: Psicologia Experimental e Educação do excepcional. Helena Antipoff dirigiu o Laboratório de Psicologia da Escola de Aperfeiçoamento de Belo Horizonte, instituição de formação de professores e técnicos em Educação. Processos de homogeneização de classes faziam parte da reforma proposta a partir de 1927. Durante a implantação das classes homogêneas, entre 1930 e 1935, a psicóloga russa fez uma crítica à limitação dessa ação isolada e concluiu que apenas a homogeneização não traria resultados suficientes para a aprendizagem e o desenvolvimento dos alunos. Antipoff empenhou-se em propor programas que pudessem oferecer à criança um ensino que respeitasse suas particularidades, ao mesmo tempo que treinasse professores para sua execução. Um desses programas era a Ortopedia Mental, técnica utilizada por Binet, e para a qual a educadora adaptou princípios educacionais e procedimentos de vários autores. Na aplicação da Ortopedia Mental, Helena Antipoff valorizava o empenho, a criatividade e o envolvimento que o professor deveria ter com sua classe na elaboração de atividades capazes de despertar o interesse das crianças e desenvolver, ao mesmo tempo, suas faculdades mentais.

ABSTRACT: The present research investigated the Mental Orthopedics method developed by the educator Helena Antipoff, focusing on its theoretical foundations. As sources, we have used the educator's texts written in the 1930's and compiled into two volumes of The Collection of Helena Antipoff's writings: Experimental Psychology and Education of Exceptional Students. Helena Antipoff directed the Psychology Laboratory of Belo Horizonte Improvement School, an institution designed for training teachers and technicians in education. Class homogenization was part of the proposed reform from 1927 on. During the implementation of homogeneous classes, between 1930 and 1935, the Russian psychologist criticized the limitations of this isolated action and concluded that homogenization alone would not bring sufficient results to the students' learning and development. Antipoff endeavored to propose programs that could offer the child an education that respected the students' particularities and offered the teachers the required training to carry out the program. One of these programs was the Mental Orthopedics, a technique used by Binet, and to which the educator adapted educational principles and procedures from several authors. In the application of the Mental Orthopedics, Helena Antipoff valued the commitment, the creativity and the involvement the teacher should have before their students when developing activities that stimulated children's interest and, at the same time, developed their mental skills.

Transcriptional Interference Promotes Rapid Expression Divergence of Drosophila Nested Genes.

Nested genes are the most common form of protein-coding overlap in eukaryotic genomes. Previous studies have shown that nested genes accumulate rapidly over evolutionary time, typically via the insertion of short young duplicate genes into long introns. However, the evolutionary relationship between nested genes remains unclear. Here, I compare RNA-seq expression profiles of nested, proximal intra-chromosomal, intermediate intra-chromosomal, distant intra-chromosomal, and inter-chromosomal gene pairs in two Drosophila species. I find that expression profiles of nested genes are more divergent than those of any other class of genes, supporting the hypothesis that concurrent expression of nested genes is deleterious due to transcriptional interference. Further analysis reveals that expression profiles of derived nested genes are more divergent than those of their ancestral un-nested orthologs, which are more divergent than those of un-nested genes with similar genomic features. Thus, gene expression divergence between nested genes is likely caused by selection against nesting of genes with insufficiently divergent expression profiles, as well as by continued expression divergence after nesting. Moreover, expression divergence and sequence evolutionary rates are elevated in young nested genes and reduced in old nested genes, indicating that a burst of rapid evolution occurs after nesting. Together, these findings suggest that similarity between expression profiles of nested genes is deleterious due to transcriptional interference, and that natural selection addresses this problem both by eradicating highly deleterious nestings and by enabling rapid expression divergence of surviving nested genes, thereby quickly limiting or abolishing transcriptional interference.

CDROM: Classification of Duplicate gene RetentiOn Mechanisms.

BACKGROUND: Gene duplication is a major source of new genes that is thought to play an important role in phenotypic innovation. Though several mechanisms have been hypothesized to drive the functional evolution and long-term retention of duplicate genes, there are currently no software tools for assessing their genome-wide contributions. Thus, the evolutionary mechanisms by which duplicate genes acquire novel functions remain unclear in a number of taxa. RESULTS: In a recent study, researchers developed a phylogenetic approach that uses gene expression data from two species to classify the mechanisms underlying the retention of duplicate genes (Proc Natl Acad Sci USA 110:1740917414, 2013). We have implemented their classification method, as well as a more generalized method, in the R package CDROM, enabling users to apply these methods to their data and gain insights into the origin of novel biological functions after gene duplication. The CDROM R package, source code, and user manual for the R package are available for download from CRAN at https://cran.rstudio.com/web/packages/CDROM/ . Additionally, the CDROM R source code, user manual for running CDROM from the source code, and sample dataset used in this manuscript can be accessed at www.personal.psu.edu/rua15/software.html . CONCLUSIONS: CDROM is the first software package that enables genome-wide classification of the mechanisms driving the long-term retention of duplicate genes. It is user-friendly and flexible, providing researchers with a tool for studying the functional evolution of duplicate genes in a variety of taxa.

Rapid divergence and diversification of mammalian duplicate gene functions.

BACKGROUND: Gene duplication provides raw material for the evolution of functional innovation. We recently developed a phylogenetic method that classifies evolutionary processes driving the retention of duplicate genes by quantifying divergence between their spatial gene expression profiles and that of their single-copy orthologous gene in a closely related sister species. RESULTS: Here, we apply our classification method to pairs of duplicate genes in eight mammalian genomes, using data from 11 tissues to construct spatial gene expression profiles. We find that young mammalian duplicates are often functionally conserved, and that expression divergence rapidly increases over evolutionary time. Moreover, expression divergence results in increased tissue specificity, with an overrepresentation of expression in male kidney, underrepresentation of expression in female liver, and strong underrepresentation of expression in testis. Thus, duplicate genes acquire a diversity of new tissue-specific functions outside of the testis, possibly contributing to the origin of a multitude of complex phenotypes during mammalian evolution. CONCLUSIONS: Our findings reveal that mammalian duplicate genes are initially functionally conserved, and then undergo rapid functional divergence over evolutionary time, acquiring diverse tissue-specific biological roles. These observations are in stark contrast to the much faster expression divergence and acquisition of broad housekeeping roles we previously observed in Drosophila duplicate genes. Due to the smaller effective population sizes of mammals relative to Drosophila, these analyses implicate natural selection in the functional evolution of duplicate genes.