RESUMEN
The male-biased prevalence of certain neurodevelopmental disorders and the sex-biased outcomes associated with stress exposure during gestation have been previously described. Here, we hypothesized that genes distinctively targeted by only one or both homologous proteins highly conserved across therian mammals, SOX3 and SRY, could induce sexual adaptive changes that result in a differential risk for neurodevelopmental disorders. ChIP-seq/chip data showed that SOX3/SRY gene targets were expressed in different brain cell types in mice. We used orthologous human genes in rodent genomes to extend the number of SOX3/SRY set (1,721). These genes were later found to be enriched in five modules of coexpressed genes during the early and mid-gestation periods (FDR < 0.05), independent of sexual hormones. Genes with differential expression (24, p < 0.0001) and methylation (40, p < 0.047) between sexes were overrepresented in this set. Exclusive SOX3 or SRY target genes were more associated with the late gestational and postnatal periods. Using autism as a model sex-biased disorder, the SOX3/SRY set was enriched in autism gene databases (FDR ≤ 0.05), and there were more de novo variations from the male autism spectrum disorder (ASD) samples under the SRY peaks compared to the random peaks (p < 0.024). The comparison of coexpressed networks of SOX3/SRY target genes between male autism and control samples revealed low preservation in gene modules related to stress response (99 genes) and neurogenesis (78 genes). This study provides evidence that while SOX3 is a regulatory mechanism for both sexes, the male-exclusive SRY also plays a role in gene regulation, suggesting a potential mechanism for sex bias in ASD.
Asunto(s)
Trastornos del Neurodesarrollo/genética , Factores de Transcripción SOXB1/genética , Proteína de la Región Y Determinante del Sexo/genética , Animales , Trastorno del Espectro Autista/genética , Proteínas de Unión al ADN/genética , Bases de Datos Genéticas , Femenino , Regulación de la Expresión Génica/genética , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Factores de Riesgo , Factores de Transcripción SOXB1/metabolismo , Cromosomas Sexuales/genética , Factores Sexuales , Proteína de la Región Y Determinante del Sexo/metabolismo , Factores de Transcripción/genéticaRESUMEN
Cecropins and defensins are the main classes of antimicrobial peptides in the mosquito innate immune system, acting against bacteria, fungi and protozoa. There is a knowledge gap concerning these peptide genes in anopheline mosquitoes from the Brazilian Amazon. Thus, this work aimed to describe molecular techniques for detecting the genes encoding the antimicrobial peptides cecropin A (CecA) and defensin in Anopheles darlingi mosquitoes and to perform molecular phylogeny of the sequenced genes using the maximum likelihood method and Bayesian inference with other species from different geographic areas. Our results show, for the first time, a molecular biology method for detecting CecA and defensin in Anopheles darlingi that allows for the use of these molecular markers for phylogenetic analysis in anopheline species, separating the species into single and monophyletic clades.
Asunto(s)
Anopheles , Cecropinas , Animales , Anopheles/genética , Péptidos Antimicrobianos , Teorema de Bayes , Cecropinas/genética , Cecropinas/farmacología , Defensinas/genética , Defensinas/farmacología , FilogeniaRESUMEN
The Nuneztovari Complex of Anopheles (Diptera: Culicidae) comprises four species: An. nuneztovari Gabaldon, An. goeldii Rozeboom Gabaldon, An. dunhami Causey and An. nuneztovari species A. This study aimed to identify morphologically the species of the Nuneztovari Complex that occur in the area of the Belo Monte hydroelectric dam. The morphological identification of adult males and male genitalia (aedeagus and ventral claspette) was performed. A statistical analysis of the difference in aedeagal leaflet length was done using the Mann-Whitney test. Of the 38 male genitalia of specimens of the Nuneztovari Complex examined, 33 were identified as An. goeldii/An. nuneztovari A and five as An. nuneztovari s.s. A statistically significant difference in aedeagal leaflet length was detected between the species: the mean length was 1.23 µm for An. goeldii/An. nuneztovari A and 9.18 µm for An. nuneztovari s.s. This is the first record of An. nuneztovari s.s.in areas of environmental modification in the Brazilian Amazon. This study provides a measurement tool that can identify and differentiate species of the complex in the region, which can be applied to the other species of the complex as well to other anopheline species; thus, fostering the acquisition of information about the role of each species in malaria transmission.