Genetic Innovation Research Articles

Deciphering recent transposition patterns in plants through comparison of 811 genome assemblies.

Transposable elements (TEs) are significant drivers of genome evolution, yet their recent dynamics and impacts within and among species, as well as the roles of host genes and non-coding RNAs in the transposition process, remain elusive. With advancements in large-scale pan-genome sequencing and the development of open data sharing, large-scale comparative genomics studies have become feasible. Here, we performed complete de novo TE annotations and identified active TEs in 310 plant genome assemblies across 119 species and seven crop populations. Using 811 high-quality genomes, we detected 13 844 553 TE-induced structural variants (TE-SVs), providing unprecedented resolution in delineating recent TE activities. Our integrative analysis revealed a mutual evolutionary relationship between TEs and host genomes. On one hand, host genes and ncRNAs are involved in the transposition process, as evidenced by their colocalization and coactivation with TEs, and may play a role in chromatin regulation. On the other hand, TEs drive genetic innovation by promoting the duplication of host genes and inserting into regulatory regions. Moreover, genes influenced by active TEs are linked to plant growth, nutrient absorption, storage metabolism and environmental adaptation, aiding in crop domestication and adaptation. This TE dynamics atlas not only reveals evolutionary and functional features linked to transposition activity but also highlights the role of TEs in crop domestication and adaptation, paving the way for future exploration of TE-mediated genome evolution and crop improvement strategies.

Enhancing the nutritional profile of rice by targeting starch branching enzymes using CRISPR/Cas9

Rice is a fundamental staple in many Asian countries; however, excessive consumption can lead to significant health concerns, including diabetes. One effective strategy to mitigate these concerns is to increase the amylose content in rice, which enhances its resistant starch (RS) levels. Higher RS not only improves the nutritional profile of rice but also positively impacts its cooking qualities, offering various health benefits. Recent research highlights the role of dietary fibers like RS in modulating gut microbiota composition, presenting a promising approach for addressing non-communicable diseases. RS enhances the fermentation activity of gut microbiota, leading to production of beneficial metabolites that support gut barrier function, exhibit anti-inflammatory properties and influence metabolic pathways related to obesity and diabetes. This multifaceted impact on chronic disease outcomes emphasizes the need for rice varieties with increased amylose and consequently higher RS levels, to meet consumer nutritional demands. CRISPR/Cas9, a powerful genome editing tool, allows precise modifications of the targeted genes. This technology can effectively edit starch synthesis-related genes in rice to enhance starch content. This review focuses on the application of CRISPR/Cas9 in increasing RS content in rice and the potential health benefits it could provide to populations that rely on rice as a dietary staple. By integrating genetic innovation with nutritional science, healthier rice varieties can be developed, that align with the dietary needs of consumers.

Initiation and stability of self-harm in adolescence and early adulthood: investigating social and aetiological factors in twins.

Almost one in five (18.8%) UK adolescents are estimated to self-harm and many young people initiate self-harm early (average age 13 years). Prevention of self-harm should be informed by knowledge about risk factors (e.g. socio-demographic indices), characteristics (i.e. motivation for self-harm and help-seeking behaviours), as well as relative aetiological genetic and environmental processes. Previous twin studies evidence both genetic and environmental influences on self-harm. However, to date, there has been no genetically informed research on self-harm aetiology across development, nor studies identifying risk factors for initiating self-harm at a younger age. We examined self-harm in the Twins Early Development Study, a birth cohort twin study. Using clustered regression models, we tested associations of socio-demographic factors and victimisation with lifetime self-harm and age of self-harm initiation, both reported at 21. To investigate stability and/or change in genetic and environmental influences on self-harm we interpreted a multivariate Cholesky decomposition across ages ≤16, 21, and 26. Self-harm was more common in adolescence than early adulthood, and the incidence of self-harm in early adulthood was low (1.4%). The most common motivation for self-harm was 'to get relief from a terrible state of mind' (83.4%). Independent predictors of self-harm and earlier initiation of self-harm were being female, belonging to a gender and/or sexual minority group, and experience of bullying victimisation. Sexual minority status was still significantly associated with self-harm after controlling for familial factors in co-twin control analyses. The Cholesky decomposition showed stability in genetic influences and innovation in non-shared environmental influences on self-harm. Adolescence should be a key period for self-harm interventions. Women, sexual, and gender minorities, and those experiencing victimisation may need targeted support early in adolescence. Furthermore, it should be acknowledged that different individuals can be at risk at different stages as environmental factors influencing self-harm change across time.

Comprehensive Exploration of Biomedical Science in Transforming Global Health

Biomedical science has supervised tremendous changes in what the world considers health and how diseases are prevented, diagnosed, and treated. From the discovery of vaccines and diagnostic aids to innovations in genetics and genomic personalized medicine, spot the discipline as a key determinant of advancing the delivery and models of health Systems globally. This paper aims to review the effect of biomedical science on global health with a focus on retrospect and prospects of diseases, health, and crises. Thus, relying on up-to-date research, cases, and world health studies, the work reveals successes and failures. As for recommendations, they are to encourage innovation, extend the usage of biomedical technologies and involve individuals and disciplines expecting to make a positive change in the coming years that is stable and effective.Biomedical Science

The lawc gene emerged de novo from conserved genomic elements and acquired a broad expression pattern in Drosophila.

It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms. De novo genes frequently emerge in proximity to existing genes, forming gene overlaps. Here, we present an analysis of the evolutionary history of a putative de novo gene, lawc, which overlaps with the conserved Trf2 gene, which encodes a general transcription factor in Drosophila melanogaster. We demonstrate that lawc emerged approximately 68 million years ago in the 5'-untranslated region of Trf2 and displays an extensive spatiotemporal expression pattern. One of the most remarkable features of the lawc evolutionary history is that its emergence was facilitated by the engagement of Drosophilidae-specific short highly conserved regions located in Trf2 introns. This represents a unique example of putative de novo gene birth involving conserved DNA regions localized in introns of conserved gene. The observed lawc expression pattern may be due to overlap of lawc with the 5'-untranslated region of Trf2. This study not only enriches our understanding of gene evolution but also highlights the complex interplay between genetic conservation and innovation.

Hidden evolutionary constraints dictate the retention of coronavirus accessory genes.

Coronaviruses exhibit many mechanisms of genetic innovation, including the acquisition of accessory genes that originate by capture of cellular genes or through duplication of existing viral genes. Accessory genes influence viral host range and cellular tropism, but little is known about how selection acts on these variable regions of virus genomes. We used experimental evolution of mouse hepatitis virus (MHV) encoding a cellular AKAP7 phosphodiesterase and an inactive native phosphodiesterase, NS2, to model the evolutionary fate of accessory genes. After courses of serial infection, the gene encoding inactive NS2, ORF2, unexpectedly remained intact, suggesting it is under cryptic constraint uncoupled from the function of NS2. By contrast, AKAP7 was retained under strong selection but rapidly lost under relaxed selection. Experimental evolution also led to altered viral replication in a cell-type-specific manner and changed the relative proportions of subgenomic viral RNA in plaque-purified viral isolates, revealing additional mechanisms of adaptation. Guided by the retention of MHV ORF2 and similar patterns in related betacoronaviruses, we analyzed ORF8 of SARS-CoV-2, which is proposed to have arisen via gene duplication and contains premature stop codons in several globally successful lineages. As with MHV ORF2, the coding-defective SARS-CoV-2 ORF8 gene remained largely intact in these lineages, mirroring patterns observed during MHV experimental evolution, challenging assumptions on the dynamics of gene loss in virus genomes, and extending these findings to viruses currently adapting to humans.

Function and Evolution of the Plant MES Family of Methylesterases.

Land plant evolution has been marked by numerous genetic innovations, including novel catalytic reactions. Plants produce various carboxyl methyl esters using carboxylic acids as substrates, both of which are involved in diverse biological processes. The biosynthesis of methyl esters is catalyzed by SABATH methyltransferases, and understanding of this family has broadened in recent years. Meanwhile, the enzymes catalyzing demethylation-known as methylesterases (MESs)-have received less attention. Here, we present a comprehensive review of the plant MES family, focusing on known biochemical and biological functions, and evolution in the plant kingdom. Thirty-two MES genes have been biochemically characterized, with substrates including methyl esters of plant hormones and several other specialized metabolites. One characterized member demonstrates non-esterase activity, indicating functional diversity in this family. MES genes regulate biological processes, including biotic and abiotic defense, as well as germination and root development. While MES genes are absent in green algae, they are ubiquitous among the land plants analyzed. Extant MES genes belong to three groups of deep origin, implying ancient gene duplication and functional divergence. Two of these groups have yet to have any characterized members. Much remains to be uncovered about the enzymatic functions, biological roles, and evolution of the MES family.

From decay to decadence: Fungal alchemy in waste valorization

Fungal alchemy harnesses fungi's enzymatic efficiency to naturally degrade synthetic plastics. Enzymes like cutinase and lipase, secreted by Aspergillus and Penicillium, break down plastics, while lignocellulolytic enzymes and oxidant ions aid in this process. Aspergillus nidulans, Bjerkandera adusta, and Pleurotus ostreatus drive bioenergy and genetic engineering innovations for a sustainable eco-friendly approach to plastic waste management and waste valorization.

Molecular Innovations Shaping Beak Morphology in Birds.

The beak, a pivotal evolutionary trait characterized by high morphological diversity and plasticity, has enabled birds to survive mass extinction events and subsequently radiate into diverse ecological niches worldwide. This remarkable ecological adaptability underscores the importance of uncovering the molecular mechanisms shaping avian beak morphology, particularly benefiting from the rapidly advancing archives of genomics and epigenomics. We review the latest advancements in understanding how genetic and epigenetic innovations control or regulate beak development and drive beak morphological adaptation and diversification over the past two decades. We conclude with several recommendations for future endeavors, expanding to more bird lineages, with a focus on beak shape and the lower beak, and conducting functional experiments. By directing research efforts toward these aspects and integrating advanced omics techniques, the complex molecular mechanisms involved in avian beak evolution and morphogenesis will be deeply interpreted.

Impact of Polyploidy on Crop Improvement and Plant Breeding Strategies: A Review

Polyploidy, the condition of possessing multiple sets of chromosomes, is a widespread phenomenon in plants that has had a profound impact on crop evolution and improvement. This review explores the role of polyploidy in plant breeding strategies, emphasizing its contributions to enhancing agronomic traits, overcoming genetic barriers, and expanding genetic diversity. Polyploid crops, such as wheat, cotton, and Brassica species, exhibit superior yield, increased biomass, and enhanced stress tolerance compared to their diploid counterparts. Polyploidy can arise naturally or be induced artificially, providing breeders with opportunities to create novel crop varieties through synthetic polyploidization. The complexity of polyploid genomes poses significant challenges, including fertility issues, meiotic instability, and difficulties in genome management. Advances in genomic and biotechnological tools, such as genomic selection and CRISPR-based genome editing, are beginning to address these obstacles, allowing for precise manipulation of polyploid genomes and improved breeding outcomes. Additionally, polyploidy plays a crucial role in overcoming reproductive barriers in interspecific hybrids, facilitating the transfer of desirable traits between species that would otherwise be genetically incompatible. The potential of polyploidy for developing climate-resilient crops is particularly noteworthy, as polyploid plants often exhibit greater tolerance to drought, salinity, and extreme temperatures. This makes polyploid breeding a promising approach for addressing the challenges of climate change and ensuring food security. Future research should focus on understanding the genetic and epigenetic mechanisms underlying polyploid genome stability and trait expression, as well as integrating advanced computational tools to predict and manipulate polyploid gene function. Emerging areas such as synthetic biology and multi-omics integration will further enhance our ability to engineer polyploid crops with complex trait architectures. Polyploidy remains a powerful and versatile tool for plant breeders, offering immense potential for crop improvement, genetic innovation, and the development of resilient agricultural systems. As the understanding and technological capabilities in polyploid breeding continue to advance, polyploid crops will play a central role in sustainable agricultural development and global food production.

The clinical actionability of genes: A concept for rare diseases and the first objective assessment for myopathies

High-throughput sequencing has introduced the concept of "actionable genes". These genes are linked to diseases for which specific treatments or care exist. Accurate genetic diagnosis is therefore crucial for initiating interventions that can prevent or delay the progression of rare diseases. High-throughput sequencing has considerably increased the capacities of genetic analyses, but it has also led to an increase in requests for analyses, lengthening the time taken to obtain results. It is becoming necessary to prioritize analyses, especially when "actionable genes" are suspected to be implicated. In the case of myopathies, a French national study has identified 63 actionable genes, implicated in diseases for which a targeted treatment and/or priority care can be initiated, thereby improving the patient's prognosis. Despite advances, many rare diseases remain without specific treatments, underlining the continuing importance of research and innovation in medical genetics.

Advances in Soybean Genetic Improvement.

The soybean (Glycine max) is a globally important crop due to its high protein and oil content, which serves as a key resource for human and animal nutrition, as well as bioenergy production. This review assesses recent advancements in soybean genetic improvement by conducting an extensive literature analysis focusing on enhancing resistance to biotic and abiotic stresses, improving nutritional profiles, and optimizing yield. We also describe the progress in breeding techniques, including traditional approaches, marker-assisted selection, and biotechnological innovations such as genetic engineering and genome editing. The development of transgenic soybean cultivars through Agrobacterium-mediated transformation and biolistic methods aims to introduce traits such as herbicide resistance, pest tolerance, and improved oil composition. However, challenges remain, particularly with respect to genotype recalcitrance to transformation, plant regeneration, and regulatory hurdles. In addition, we examined how wild soybean germplasm and polyploidy contribute to expanding genetic diversity as well as the influence of epigenetic processes and microbiome on stress tolerance. These genetic innovations are crucial for addressing the increasing global demand for soybeans, while mitigating the effects of climate change and environmental stressors. The integration of molecular breeding strategies with sustainable agricultural practices offers a pathway for developing more resilient and productive soybean varieties, thereby contributing to global food security and agricultural sustainability.

A review on achromatopsia: Exploring genetic basis, diagnostic innovations, and therapeutic prospects

Achromatopsia (ACHM) is a rare inherited retinal disorder characterized by partial or complete color blindness, which impacts individuals' quality of life and daily functioning. This review delves into the genetic basis, diagnostic innovations, and therapeutic prospects associated with ACHM. The main objective is to comprehensively explore the current understanding of ACHM, including genetic mutations, diagnostic techniques, and management approaches, while also discussing potential therapeutic interventions. Achromatopsia primarily results from mutations in genes encoding cone photoreceptor proteins, such as GNAT2, ATF6, PDE6H, PDE6C, CNGA3, and CNGB3. Various diagnostic methods, including electroretinography (ERG) and optical coherence tomography (OCT), are pivotal in confirming ACHM diagnosis by assessing cone function and structural abnormalities in dysfunctional cone cells. This review also highlights gene therapy interventions aimed at restoring cone function, highlighting promising advancements in preclinical and clinical settings. Additionally, it discusses the clinical features of ACHM, such as reduced visual acuity, photophobia, and color vision impairment, emphasizing the need for tailored management strategies to increase patients' quality of life. This review underscores the complex genetic landscape of ACHM and the importance of accurate diagnosis through advanced diagnostic modalities such as ERG and OCT. While there is currently no cure for ACHM, management approaches focus on symptom alleviation and improving patients' daily functioning. Gene therapy has emerged as a promising avenue for potential treatment, with ongoing research aiming to address the underlying genetic defects and restore cone photoreceptor function. The findings of this review hold clinical relevance by providing insights into the pathogenesis, diagnosis, and management of ACHM, guiding healthcare professionals in delivering personalized care to affected individuals. Continued research and advancements in gene therapy offer hope for future therapeutic interventions, highlighting the importance of updating the latest developments in the field of ACHM.

Hidden evolutionary constraints dictate the retention of coronavirus accessory genes.

Coronaviruses exhibit many mechanisms of genetic innovation, including the acquisition of accessory genes that originate by capture of cellular genes or through duplication of existing viral genes. Accessory genes influence viral host range and cellular tropism, but little is known about how selection acts on these variable regions of virus genomes. We used experimental evolution of mouse hepatitis virus (MHV) encoding a cellular AKAP7 phosphodiesterase and an inactive native phosphodiesterase, NS2 to model the evolutionary fate of accessory genes. After courses of serial infection, the gene encoding inactive NS2, ORF2, unexpectedly remained intact, suggesting it is under cryptic constraint uncoupled from the function of NS2. In contrast, AKAP7 was retained under strong selection but rapidly lost under relaxed selection. Experimental evolution also led to altered viral replication in a cell type-specific manner and changed the relative proportions of subgenomic viral RNA in plaque-purified viral isolates, revealing additional mechanisms of adaptation. Guided by the retention of ORF2 and similar patterns in related betacoronaviruses, we analyzed ORF8 of SARS-CoV-2, which arose via gene duplication and contains premature stop codons in several globally successful lineages. As with MHV ORF2, the coding-defective SARS-CoV-2 ORF8 gene remains largely intact, mirroring patterns observed during MHV experimental evolution, challenging assumptions on the dynamics of gene loss in virus genomes and extending these findings to viruses currently adapting to humans.

9269 Retrotranscribed sequences, a missing piece in the puzzle of Differences/Disorders of Sex Development with unknown genetic causes

Abstract Disclosure: R.L. Batista: None. N.D. D’Alessandre: None. F.O. Rego: None. G.D. Guardia: None. B. Leitao Braga: None. M.Y. Nishi: None. S. Domenice: None. B.B. Mendonca: None. P.A. Galante: None. Background: The human genome is a complex and dynamic structure. These two characteristics have a major contribution from the Mobile Elements (MEs), which comprise at least 50% of the human genome and are sources of genetic novelties. LINE1 (L1), Alu elements, SVA, and LTR elements (HERVs) are MEs highly frequent in the human genome. MEs can create genomic structural variations with consequent roles in health and diseases. Differences of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual’s sex chromosomes, gonads, or anatomic sex. DSDs are caused by genomic variations in genes involved in gonadal or genital development.Objective: We comprehensively examine the potential contributions of MEs as a source of genetic novelties in genes related to sexual development and in the etiology of 46,XY DSD. Subjects and methods: First, we investigate the potential role of fixed MEs, including L1, Alu elements, and retroCNVs, present in DSD genes using whole exome sequencing (WES) data. By applying bioinformatics tools and appropriate pipelines, we parallelly analyzed local WES data from 443 individuals from our lab and a public database (GnomAD). Second, we seek unfixed (polymorphic or somatically acquired) MEs in WES data from a cohort of 41 unrelated DSD patients with undetermined molecular etiology. We found 2,408 L1 elements, 3,587 Alu elements, and 14 SVAs inserted in 75 out of 81 DSD-related genes (92.6%) of the DSD genes. When examining by element class, we identified 3,587 fixed Alus that affected over 70 DSD genes, resulting in an average of approximately 47 Alu element insertions per gene. For L1 elements, 2,408 fixed elements were found in about 60 genes (∼37 insertions per gene). Subsequently, the number of fixed elements identified in SVAs (n=14) and HERVKs (n=8) decreased significantly. Among these insertions, seven genes were identified harboring one retrocopy each and four genes with two or more retrocopies each. In total, we found 19 retrocopies in 11 DSD genes. That massive presence of mobile elements in DSD genes may suggest an evolutionary contribution of MEs incorporation through evolution in human sexual development. Regarding non-fixed elements, we found two polymorphic events: an L1 insertion into WT1 and an Alu insertion into GTF2F1, two key genes to the DSD development. We also found an L1 insertion in the DNAH2 gene (related to spermatogenic failure and male infertility) and an Alu insertion in the TEX15 gene (related to male infertility in mice). Interestingly, we also identified one somatically acquired retroCNV event in a non-classical DSD gene (CHST8). In summary, our study underscores the significance of MEs as potential sources of genetic innovation in human sexual development and as molecular etiologies of DSD. Presentation: 6/1/2024

9269 Retrotranscribed sequences, a missing piece in the puzzle of Differences/Disorders of Sex Development with unknown genetic causes

Abstract Disclosure: R.L. Batista: None. N.D. D’Alessandre: None. F.O. Rego: None. G.D. Guardia: None. B. Leitao Braga: None. M.Y. Nishi: None. S. Domenice: None. B.B. Mendonca: None. P.A. Galante: None. Background: The human genome is a complex and dynamic structure. These two characteristics have a major contribution from the Mobile Elements (MEs), which comprise at least 50% of the human genome and are sources of genetic novelties. LINE1 (L1), Alu elements, SVA, and LTR elements (HERVs) are MEs highly frequent in the human genome. MEs can create genomic structural variations with consequent roles in health and diseases. Differences of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual’s sex chromosomes, gonads, or anatomic sex. DSDs are caused by genomic variations in genes involved in gonadal or genital development.Objective: We comprehensively examine the potential contributions of MEs as a source of genetic novelties in genes related to sexual development and in the etiology of 46,XY DSD. Subjects and methods: First, we investigate the potential role of fixed MEs, including L1, Alu elements, and retroCNVs, present in DSD genes using whole exome sequencing (WES) data. By applying bioinformatics tools and appropriate pipelines, we parallelly analyzed local WES data from 443 individuals from our lab and a public database (GnomAD). Second, we seek unfixed (polymorphic or somatically acquired) MEs in WES data from a cohort of 41 unrelated DSD patients with undetermined molecular etiology. We found 2,408 L1 elements, 3,587 Alu elements, and 14 SVAs inserted in 75 out of 81 DSD-related genes (92.6%) of the DSD genes. When examining by element class, we identified 3,587 fixed Alus that affected over 70 DSD genes, resulting in an average of approximately 47 Alu element insertions per gene. For L1 elements, 2,408 fixed elements were found in about 60 genes (∼37 insertions per gene). Subsequently, the number of fixed elements identified in SVAs (n=14) and HERVKs (n=8) decreased significantly. Among these insertions, seven genes were identified harboring one retrocopy each and four genes with two or more retrocopies each. In total, we found 19 retrocopies in 11 DSD genes. That massive presence of mobile elements in DSD genes may suggest an evolutionary contribution of MEs incorporation through evolution in human sexual development. Regarding non-fixed elements, we found two polymorphic events: an L1 insertion into WT1 and an Alu insertion into GTF2F1, two key genes to the DSD development. We also found an L1 insertion in the DNAH2 gene (related to spermatogenic failure and male infertility) and an Alu insertion in the TEX15 gene (related to male infertility in mice). Interestingly, we also identified one somatically acquired retroCNV event in a non-classical DSD gene (CHST8). In summary, our study underscores the significance of MEs as potential sources of genetic innovation in human sexual development and as molecular etiologies of DSD. Presentation: 6/1/2024

8703 Retrotranscribed sequences, a missing piece in the puzzle of Differences/Disorders of Sex Development with unknown genetic causes

Abstract Disclosure: R.L. Batista: None. N.D. D’Alessandre: None. F.O. Rego: None. G.D. Guardia: None. B. Leitao Braga: None. M.Y. Nishi: None. S. Domenice: None. B.B. Mendonca: None. P.A. Galante: None. Background: The human genome is a complex and dynamic structure. These two characteristics have a major contribution from the Mobile Elements (MEs), which comprise at least 50% of the human genome and are sources of genetic novelties. LINE1 (L1), Alu elements, SVA, and LTR elements (HERVs) are MEs highly frequent in the human genome. MEs can create genomic structural variations with consequent roles in health and diseases. Differences of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual’s sex chromosomes, gonads, or anatomic sex. DSDs are caused by genomic variations in genes involved in gonadal or genital development.Objective: We comprehensively examine the potential contributions of MEs as a source of genetic novelties in genes related to sexual development and in the etiology of 46,XY DSD. Subjects and methods: First, we investigate the potential role of fixed MEs, including L1, Alu elements, and retroCNVs, present in DSD genes using whole exome sequencing (WES) data. By applying bioinformatics tools and appropriate pipelines, we parallelly analyzed local WES data from 443 individuals from our lab and a public database (GnomAD). Second, we seek unfixed (polymorphic or somatically acquired) MEs in WES data from a cohort of 41 unrelated DSD patients with undetermined molecular etiology. We found 2,408 L1 elements, 3,587 Alu elements, and 14 SVAs inserted in 75 out of 81 DSD-related genes (92.6%) of the DSD genes. When examining by element class, we identified 3,587 fixed Alus that affected over 70 DSD genes, resulting in an average of approximately 47 Alu element insertions per gene. For L1 elements, 2,408 fixed elements were found in about 60 genes (∼37 insertions per gene). Subsequently, the number of fixed elements identified in SVAs (n=14) and HERVKs (n=8) decreased significantly. Among these insertions, seven genes were identified harboring one retrocopy each and four genes with two or more retrocopies each. In total, we found 19 retrocopies in 11 DSD genes. That massive presence of mobile elements in DSD genes may suggest an evolutionary contribution of MEs incorporation through evolution in human sexual development.Regarding non-fixed elements, we found two polymorphic events: an L1 insertion into WT1 and an Alu insertion into GTF2F1, two key genes to the DSD development. We also found an L1 insertion in the DNAH2 gene (related to spermatogenic failure and male infertility) and an Alu insertion in the TEX15 gene (related to male infertility in mice). Interestingly, we also identified one somatically acquired retroCNV event in a non-classical DSD gene (CHST8). In summary, our study underscores the significance of MEs as potential sources of genetic innovation in human sexual development and as molecular etiologies of DSD. Presentation: 6/1/2024

8703 Retrotranscribed sequences, a missing piece in the puzzle of Differences/Disorders of Sex Development with unknown genetic causes

Abstract Disclosure: R.L. Batista: None. N.D. D’Alessandre: None. F.O. Rego: None. G.D. Guardia: None. B. Leitao Braga: None. M.Y. Nishi: None. S. Domenice: None. B.B. Mendonca: None. P.A. Galante: None. Background: The human genome is a complex and dynamic structure. These two characteristics have a major contribution from the Mobile Elements (MEs), which comprise at least 50% of the human genome and are sources of genetic novelties. LINE1 (L1), Alu elements, SVA, and LTR elements (HERVs) are MEs highly frequent in the human genome. MEs can create genomic structural variations with consequent roles in health and diseases. Differences of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual’s sex chromosomes, gonads, or anatomic sex. DSDs are caused by genomic variations in genes involved in gonadal or genital development.Objective: We comprehensively examine the potential contributions of MEs as a source of genetic novelties in genes related to sexual development and in the etiology of 46,XY DSD. Subjects and methods: First, we investigate the potential role of fixed MEs, including L1, Alu elements, and retroCNVs, present in DSD genes using whole exome sequencing (WES) data. By applying bioinformatics tools and appropriate pipelines, we parallelly analyzed local WES data from 443 individuals from our lab and a public database (GnomAD). Second, we seek unfixed (polymorphic or somatically acquired) MEs in WES data from a cohort of 41 unrelated DSD patients with undetermined molecular etiology. We found 2,408 L1 elements, 3,587 Alu elements, and 14 SVAs inserted in 75 out of 81 DSD-related genes (92.6%) of the DSD genes. When examining by element class, we identified 3,587 fixed Alus that affected over 70 DSD genes, resulting in an average of approximately 47 Alu element insertions per gene. For L1 elements, 2,408 fixed elements were found in about 60 genes (∼37 insertions per gene). Subsequently, the number of fixed elements identified in SVAs (n=14) and HERVKs (n=8) decreased significantly. Among these insertions, seven genes were identified harboring one retrocopy each and four genes with two or more retrocopies each. In total, we found 19 retrocopies in 11 DSD genes. That massive presence of mobile elements in DSD genes may suggest an evolutionary contribution of MEs incorporation through evolution in human sexual development.Regarding non-fixed elements, we found two polymorphic events: an L1 insertion into WT1 and an Alu insertion into GTF2F1, two key genes to the DSD development. We also found an L1 insertion in the DNAH2 gene (related to spermatogenic failure and male infertility) and an Alu insertion in the TEX15 gene (related to male infertility in mice). Interestingly, we also identified one somatically acquired retroCNV event in a non-classical DSD gene (CHST8). In summary, our study underscores the significance of MEs as potential sources of genetic innovation in human sexual development and as molecular etiologies of DSD. Presentation: 6/1/2024

Duplication and sub-functionalization of flavonoid biosynthesis genes plays important role in Leguminosae root nodule symbiosis evolution.

Gene innovation plays an essential role in trait evolution. Rhizobial symbioses, the most important N2-fixing agent in agricultural systems that exists mainly in Leguminosae, is one of the most attractive evolution events. However, the gene innovations underlying Leguminosae root nodule symbiosis (RNS) remain largely unknown. Here, we investigated the gene gain event in Leguminosae RNS evolution through comprehensive phylogenomic analyses. We revealed that Leguminosae-gain genes were acquired by gene duplication and underwent a strong purifying selection. Kyoto Encyclopedia of Genes and Genomes analyses showed that the innovated genes were enriched in flavonoid biosynthesis pathways, particular downstream of chalcone synthase (CHS). Among them, Leguminosae-gain type Ⅱ chalcone isomerase (CHI) could be further divided into CHI1A and CHI1B clades, which resulted from the products of tandem duplication. Furthermore, the duplicated CHI genes exhibited exon-intron structural divergences evolved through exon/intron gain/loss and insertion/deletion. Knocking down CHI1B significantly reduced nodulation in Glycine max (soybean) and Medicago truncatula; whereas, knocking down its duplication gene CHI1A had no effect on nodulation. Therefore, Leguminosae-gain type Ⅱ CHI participated in RNS and the duplicated CHI1A and CHI1B genes exhibited RNS functional divergence. This study provides functional insights into Leguminosae-gain genetic innovation and sub-functionalization after gene duplication that contribute to the evolution and adaptation of RNS in Leguminosae.

Review on How Genetic Innovations Revolutionizing Seed Quality Production

The process of genetic engineering modifies the genes regulating various attributes of seed quality by fabricating or redesigning some of the DNA sequences within an organism which affects germination, growth, and storage performance. Providing molecular dissection as a tool for exploiting the genetic blueprint towards the crop improvement strategy as well as improved seed yield or quality is an example showing how important it is to understand these things technically. Techniques like CRISPR and prime editing that have potential to position-specific changes in DNA sequences that helped to improve different traits such as stress resistance, productivity, nutritional value etc. Applications of transgenic approaches for boosting mineral content in certain crops different methods used to deal with micronutrient for malnutrition in developing countries. Development of good quality seeds resistant to environmental conditions are very important for agricultural sustainability under climate change. It ensures crop adaptation, food security and multiplication that must be promoted in future. The regulatory framework rightly requires safety assessments adapted to genetically modified (GM) foodstuffs which not only leads to satisfied public regarding health issues but also ethical standards concerning genetic engineering are upheld. The outcome is that by adhesion to professional ethics and strict safety measures, biotechnology possessing such qualities has been able to make revolutionary contribution into development fostered by stable agriculture system.