Journal Description
Genes
Genes
is a peer-reviewed, open access journal of genetics and genomics published monthly online by MDPI. The Spanish Society for Biochemistry and Molecular Biology (SEBBM) is affiliated with Genes and their members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, AGRIOLA, and many other databases.
- Journal Rank: JCR - Q2 (Genetics & Heredity) / CiteScore - Q2 (Genetics)
- Rapid Publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 17.4 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2021).
- Recognition of Reviewers: Reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.096 (2020)
;
5-Year Impact Factor:
4.339 (2020)
Latest Articles
Gene Annotation and Transcriptome Delineation on a De Novo Genome Assembly for the Reference Leishmania major Friedlin Strain
Genes 2021, 12(9), 1359; https://doi.org/10.3390/genes12091359 - 29 Aug 2021
Abstract
Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The
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Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The objective was successfully attained in 2005, and this represented a milestone for Leishmania molecular biology studies around the world. Although the LmjF genome sequence was done following a shotgun strategy and using classical Sanger sequencing, the results were excellent, and this genome assembly served as the reference for subsequent genome assemblies in other Leishmania species. Here, we present a new assembly for the genome of this strain (named LMJFC for clarity), generated by the combination of two high throughput sequencing platforms, Illumina short-read sequencing and PacBio Single Molecular Real-Time (SMRT) sequencing, which provides long-read sequences. Apart from resolving uncertain nucleotide positions, several genomic regions were reorganized and a more precise composition of tandemly repeated gene loci was attained. Additionally, the genome annotation was improved by adding 542 genes and more accurate coding-sequences defined for around two hundred genes, based on the transcriptome delimitation also carried out in this work. As a result, we are providing gene models (including untranslated regions and introns) for 11,238 genes. Genomic information ultimately determines the biology of every organism; therefore, our understanding of molecular mechanisms will depend on the availability of precise genome sequences and accurate gene annotations. In this regard, this work is providing an improved genome sequence and updated transcriptome annotations for the reference L. major Friedlin strain.
Full article
(This article belongs to the Special Issue Genetics and Genomics of Leishmania)
Open AccessArticle
Highly Conservative Pattern of Sex Chromosome Synapsis and Recombination in Neognathae Birds
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, , , , , and
Genes 2021, 12(9), 1358; https://doi.org/10.3390/genes12091358 - 29 Aug 2021
Abstract
We analyzed the synapsis and recombination between Z and W chromosomes in the oocytes of nine neognath species: domestic chicken Gallus gallus domesticus, grey goose Anser anser, black tern Chlidonias niger, common tern Sterna hirundo, pale martin Riparia diluta
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We analyzed the synapsis and recombination between Z and W chromosomes in the oocytes of nine neognath species: domestic chicken Gallus gallus domesticus, grey goose Anser anser, black tern Chlidonias niger, common tern Sterna hirundo, pale martin Riparia diluta, barn swallow Hirundo rustica, European pied flycatcher Ficedula hypoleuca, great tit Parus major and white wagtail Motacilla alba using immunolocalization of SYCP3, the main protein of the lateral elements of the synaptonemal complex, and MLH1, the mismatch repair protein marking mature recombination nodules. In all species examined, homologous synapsis occurs in a short region of variable size at the ends of Z and W chromosomes, where a single recombination nodule is located. The remaining parts of the sex chromosomes undergo synaptic adjustment and synapse non-homologously. In 25% of ZW bivalents of white wagtail, synapsis and recombination also occur at the secondary pairing region, which probably resulted from autosome−sex chromosome translocation. Using FISH with a paint probe specific to the germline-restricted chromosome (GRC) of the pale martin on the oocytes of the pale martin, barn swallow and great tit, we showed that both maternally inherited songbird chromosomes (GRC and W) share common sequences.
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(This article belongs to the Special Issue Sex Chromosome Evolution and Meiosis)
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Open AccessArticle
Complete Chloroplast Genomes of Fagus sylvatica L. Reveal Sequence Conservation in the Inverted Repeat and the Presence of Allelic Variation in NUPTs
Genes 2021, 12(9), 1357; https://doi.org/10.3390/genes12091357 - 29 Aug 2021
Abstract
Growing amounts of genomic data and more efficient assembly tools advance organelle genomics at an unprecedented scale. Genomic resources are increasingly used for phylogenetic analyses of many plant species, but are less frequently used to investigate within-species variability and phylogeography. In this study,
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Growing amounts of genomic data and more efficient assembly tools advance organelle genomics at an unprecedented scale. Genomic resources are increasingly used for phylogenetic analyses of many plant species, but are less frequently used to investigate within-species variability and phylogeography. In this study, we investigated genetic diversity of Fagus sylvatica, an important broadleaved tree species of European forests, based on complete chloroplast genomes of 18 individuals sampled widely across the species distribution. Our results confirm the hypothesis of a low cpDNA diversity in European beech. The chloroplast genome size was remarkably stable (158,428 ± 37 bp). The polymorphic markers, 12 microsatellites (SSR), four SNPs and one indel, were found only in the single copy regions, while inverted repeat regions were monomorphic both in terms of length and sequence, suggesting highly efficient suppression of mutation. The within-individual analysis of polymorphisms showed >9k of markers which were proportionally present in gene and non-gene areas. However, an investigation of the frequency of alternate alleles revealed that the source of this diversity originated likely from nuclear-encoded plastome remnants (NUPTs). Phylogeographic and Mantel correlation analysis based on the complete chloroplast genomes exhibited clustering of individuals according to geographic distance in the first distance class, suggesting that the novel markers and in particular the cpSSRs could provide a more detailed picture of beech population structure in Central Europe.
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(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle
A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
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, , , , , , , , , , , , , , and
Genes 2021, 12(9), 1356; https://doi.org/10.3390/genes12091356 - 29 Aug 2021
Abstract
The cell–cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on
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The cell–cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The Rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
Open AccessReview
Targeting the CDK6 Dependence of Ph+ Acute Lymphoblastic Leukemia
Genes 2021, 12(9), 1355; https://doi.org/10.3390/genes12091355 - 29 Aug 2021
Abstract
Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190- or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy,
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Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190- or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in <5-year overall survival. Thus, new therapies are needed to address relapsed/TKI-resistant Ph+ ALL. We have shown that expression of cell cycle regulatory kinase CDK6, but not of the highly related CDK4 kinase, is required for the proliferation and survival of Ph+ ALL cells. Comparison of leukemia suppression induced by treatment with the clinically-approved dual CDK4/6 inhibitor palbociclib versus CDK6 silencing revealed that the latter treatment was markedly more effective, probably reflecting inhibition of CDK6 kinase-independent effects. Thus, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that preferentially degrade CDK6 over CDK4. One compound termed PROTAC YX-2-107, which degrades CDK6 by recruiting the Cereblon ubiquitin ligase, markedly suppressed leukemia burden in mice injected with de novo or TKI-resistant Ph+ ALL. The effect of PROTAC YX-2-107 was comparable or superior to that of palbociclib. The development of CDK6-selective PROTACs represents an effective strategy to exploit the “CDK6 dependence” of Ph+ ALL cells while sparing a high proportion of normal hematopoietic progenitors that depend on both CDK6 and CDK6 for their survival. In combination with other agents, CDK6-selective PROTACs may be valuable components of chemotherapy-free protocols for the therapy of Ph+ ALL and other CDK6-dependent hematological malignancies.
Full article
(This article belongs to the Special Issue Genetics and Genomics of Blood Disorders)
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Open AccessArticle
GDF6 Knockdown in a Family with Multiple Synostosis Syndrome and Speech Impairment
Genes 2021, 12(9), 1354; https://doi.org/10.3390/genes12091354 - 29 Aug 2021
Abstract
Multiple synostoses syndrome type 4 (SYNS4; MIM 617898) is an autosomal dominant disorder characterized by carpal-tarsal coalition and otosclerosis-associated hearing loss. SYSN4 has been associated with GDF6 gain-of-function mutations. Here we report a five-generation SYNS4 family with a reduction in GDF6 expression resulting
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Multiple synostoses syndrome type 4 (SYNS4; MIM 617898) is an autosomal dominant disorder characterized by carpal-tarsal coalition and otosclerosis-associated hearing loss. SYSN4 has been associated with GDF6 gain-of-function mutations. Here we report a five-generation SYNS4 family with a reduction in GDF6 expression resulting from a chromosomal breakpoint 3′ of GDF6. A 30-year medical history of the family indicated bilateral carpal-tarsal coalition in ~50% of affected family members and acquired otosclerosis-associated hearing loss in females only, whereas vertebral fusion was present in all affected family members, most of whom were speech impaired. All vertebral fusions were acquired postnatally in progressive fashion from a very early age. Thinning across the 2nd cervical vertebral interspace (C2-3) in the proband during infancy progressed to block fusion across C2-7 and T3-7 later in life. Carpal-tarsal coalition and pisiform expansion were bilaterally symmetrical within, but varied greatly between, affected family members. This is the first report of SYNS4 in a family with reduced GDF6 expression indicating a prenatal role for GDF6 in regulating development of the joints of the carpals and tarsals, the pisiform, ears, larynx, mouth and face and an overlapping postnatal role in suppression of aberrant ossification and synostosis of the joints of the inner ear (otosclerosis), larynx and vertebrae. RNAseq gene expression analysis indicated >10 fold knockdown of NOMO3, RBMXL1 and NEIL2 in both primary fibroblast cultures and fresh white blood cells. Together these results provide greater insight into the role of GDF6 in skeletal joint development.
Full article
(This article belongs to the Special Issue Genotype-Phenotype Study in Disease)
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Open AccessReview
Bardet–Biedl Syndrome—Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype–Phenotype Correlations
Genes 2021, 12(9), 1353; https://doi.org/10.3390/genes12091353 - 29 Aug 2021
Abstract
Bardet–Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It
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Bardet–Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet–Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.
Full article
(This article belongs to the Special Issue Genotype-Phenotype Study in Disease)
Open AccessArticle
Extended Phenotyping and Functional Validation Facilitate Diagnosis of a Complex Patient Harboring Genetic Variants in MCCC1 and GNB5 Causing Overlapping Phenotypes
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Genes 2021, 12(9), 1352; https://doi.org/10.3390/genes12091352 - 29 Aug 2021
Abstract
Identifying multiple ultra-rare genetic syndromes with overlapping phenotypes is a diagnostic conundrum in clinical genetics. This study investigated the pathogenicity of a homozygous missense variant in GNB5 (GNB5L; NM_016194.4: c.920T > G (p. Leu307Arg); GNB5S; NM_006578.4: c.794T > G (p. Leu265Arg)) identified
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Identifying multiple ultra-rare genetic syndromes with overlapping phenotypes is a diagnostic conundrum in clinical genetics. This study investigated the pathogenicity of a homozygous missense variant in GNB5 (GNB5L; NM_016194.4: c.920T > G (p. Leu307Arg); GNB5S; NM_006578.4: c.794T > G (p. Leu265Arg)) identified through exome sequencing in a female child who also had 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (newborn screening positive) and hemoglobin E trait. The proband presented with early-onset intellectual disability, the severity of which was more in keeping with GNB5-related disorder than 3-MCC deficiency. She later developed bradycardia and cardiac arrest, and upon re-phenotyping showed cone photo-transduction recovery deficit, all known only to GNB5-related disorders. Patient-derived fibroblast assays showed preserved GNB5S expression, but bioluminescence resonance energy transfer assay showed abolished function of the variant reconstituted Gβ5s containing RGS complexes for deactivation of D2 dopamine receptor activity, confirming variant pathogenicity. This study highlights the need for precise phenotyping and functional assays to facilitate variant classification and clinical diagnosis in patients with complex medical conditions.
Full article
(This article belongs to the Special Issue Functional Studies for Interpreting Genetic Variants Associated with Genetic Disorders)
Open AccessArticle
Identification of Key Transcription Factors Related to Bacterial Spot Resistance in Pepper through Regulatory Network Analyses
Genes 2021, 12(9), 1351; https://doi.org/10.3390/genes12091351 - 29 Aug 2021
Abstract
Bacterial spot (BS), caused by Xanthomonas campestris pv. Vesicatoria (Xcv), severely affects the quality and yield of pepper. Thus, breeding new pepper cultivars with enhanced resistance to BS can improve economic benefits for pepper production. Identification of BS resistance genes is
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Bacterial spot (BS), caused by Xanthomonas campestris pv. Vesicatoria (Xcv), severely affects the quality and yield of pepper. Thus, breeding new pepper cultivars with enhanced resistance to BS can improve economic benefits for pepper production. Identification of BS resistance genes is an essential step to achieve this goal. However, very few BS resistance genes have been well characterized in pepper so far. In this study, we reanalyzed public multiple time points related to RNA-seq data sets from two pepper cultivars, the Xcv-susceptible cultivar ECW and the Xcv-resistant cultivar VI037601, post Xcv infection. We identified a total of 3568 differentially expressed genes (DEGs) between two cultivars post Xcv infection, which were mainly involved in some biological processes, such as Gene Ontology (GO) terms related to defense response to bacterium, immune system process, and regulation of defense response, etc. Through weighted gene co-expression network analysis (WGCNA), we identified 15 hub (Hub) transcription factor (TF) candidates in response to Xcv infection. We further selected 20 TFs from the gene regulatory network (GRN) potentially involved in Xcv resistance response. Finally, we predicted 4 TFs, C3H (p-coumarate 3-hydroxylase), ERF (ethylene-responsive element binding factor), TALE (three-amino-acid-loop-extension), and HSF (heat shock transcription factor), as key factors responsible for BS disease resistance in pepper. In conclusion, our study provides valuable resources for dissecting the underlying molecular mechanism responsible for Xcv resistance in pepper. Additionally, it also provides valuable references for mining transcriptomic data to identify key candidates for disease resistance in horticulture crops.
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(This article belongs to the Section Plant Genetics and Genomics)
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Multi-Dimensional Scaling Analysis of Key Regulatory Genes in Prostate Cancer Using the TCGA Database
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, , , , and
Genes 2021, 12(9), 1350; https://doi.org/10.3390/genes12091350 - 29 Aug 2021
Abstract
Prostate cancer (PC) is a polygenic disease with multiple gene interactions. Therefore, a detailed analysis of its epidemiology and evaluation of risk factors can help to identify more accurate predictors of aggressive disease. We used the transcriptome data from a cohort of 243
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Prostate cancer (PC) is a polygenic disease with multiple gene interactions. Therefore, a detailed analysis of its epidemiology and evaluation of risk factors can help to identify more accurate predictors of aggressive disease. We used the transcriptome data from a cohort of 243 patients from the Cancer Genome Atlas (TCGA) database. Key regulatory genes involved in proliferation activity, in the regulation of stress, and in the regulation of inflammation processes of the tumor microenvironment were selected to test a priori multi-dimensional scaling (MDS) models and create a combined score to better predict the patients’ survival and disease-free intervals. Survival was positively correlated with cortisol expression and negatively with Mini-Chromosome Maintenance 7 (MCM7) and Breast-Related Cancer Antigen2 (BRCA2) expression. The disease-free interval was negatively related to the expression of enhancer of zeste homolog 2 (EZH2), MCM7, BRCA2, and programmed cell death 1 ligand 1 (PD-L1). MDS suggested two separate pathways of activation in PC. Within these two dimensions three separate clusters emerged: (1) cortisol and brain-derived neurotrophic factor BDNF, (2) PD-L1 and cytotoxic-T-lymphocyte-associated protein 4 (CTL4); (3) and finally EZH2, MCM7, BRCA2, and c-Myc. We entered the three clusters of association shown in the MDS in several Kaplan–Meier analyses. It was found that only Cluster 3 was significantly related to the interval-disease free, indicating that patients with an overall higher activity of regulatory genes of proliferation and DNA repair had a lower probability to have a longer disease-free time. In conclusion, our data study provided initial evidence that selecting patients with a high grade of proliferation and DNA repair activity could lead to an early identification of an aggressive PC with a potentials for metastatic development.
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(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
Thousands of CpGs Show DNA Methylation Differences in ACPA-Positive Individuals
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, , , , , , , , and
Genes 2021, 12(9), 1349; https://doi.org/10.3390/genes12091349 - 29 Aug 2021
Abstract
High levels of anti-citrullinated protein antibodies (ACPA) are often observed prior to a diagnosis of rheumatoid arthritis (RA). We undertook a replication study to confirm CpG sites showing evidence of differential methylation in subjects positive vs. negative for ACPA, in a new subset
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High levels of anti-citrullinated protein antibodies (ACPA) are often observed prior to a diagnosis of rheumatoid arthritis (RA). We undertook a replication study to confirm CpG sites showing evidence of differential methylation in subjects positive vs. negative for ACPA, in a new subset of 112 individuals sampled from the population cohort and biobank CARTaGENE in Quebec, Canada. Targeted custom capture bisulfite sequencing was conducted at approximately 5.3 million CpGs located in regulatory or hypomethylated regions from whole blood; library and protocol improvements had been instituted between the original and this replication study, enabling better coverage and additional identification of differentially methylated regions (DMRs). Using binomial regression models, we identified 19,472 ACPA-associated differentially methylated cytosines (DMCs), of which 430 overlapped with the 1909 DMCs reported by the original study; 814 DMRs of relevance were clustered by grouping adjacent DMCs into regions. Furthermore, we performed an additional integrative analysis by looking at the DMRs that overlap with RA related loci published in the GWAS Catalog, and protein-coding genes associated with these DMRs were enriched in the biological process of cell adhesion and involved in immune-related pathways.
Full article
(This article belongs to the Special Issue GWAS on Special Human Phenotypes)
Open AccessReview
Mitochondrial Dysfunction in Diseases, Longevity, and Treatment Resistance: Tuning Mitochondria Function as a Therapeutic Strategy
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, , , , , and
Genes 2021, 12(9), 1348; https://doi.org/10.3390/genes12091348 - 29 Aug 2021
Abstract
Mitochondria are very important intracellular organelles because they have various functions. They produce ATP, are involved in cell signaling and cell death, and are a major source of reactive oxygen species (ROS). Mitochondria have their own DNA (mtDNA) and mutation of mtDNA or
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Mitochondria are very important intracellular organelles because they have various functions. They produce ATP, are involved in cell signaling and cell death, and are a major source of reactive oxygen species (ROS). Mitochondria have their own DNA (mtDNA) and mutation of mtDNA or change the mtDNA copy numbers leads to disease, cancer chemo/radioresistance and aging including longevity. In this review, we discuss the mtDNA mutation, mitochondrial disease, longevity, and importance of mitochondrial dysfunction in cancer first. In the later part, we particularly focus on the role in cancer resistance and the mitochondrial condition such as mtDNA copy number, mitochondrial membrane potential, ROS levels, and ATP production. We suggest a therapeutic strategy employing mitochondrial transplantation (mtTP) for treatment-resistant cancer.
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(This article belongs to the Special Issue Alterations in mtDNA and Mitochondrial Quality Control)
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Open AccessArticle
Genome Size Dynamics in Marine Ribbon Worms (Nemertea, Spiralia)
Genes 2021, 12(9), 1347; https://doi.org/10.3390/genes12091347 - 28 Aug 2021
Abstract
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
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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.
Full article
(This article belongs to the Section Animal Genetics and Genomics)
Open AccessReview
Alternative Splicing Role in New Therapies of Spinal Muscular Atrophy
Genes 2021, 12(9), 1346; https://doi.org/10.3390/genes12091346 - 28 Aug 2021
Abstract
It has been estimated that 80% of the pre-mRNA undergoes alternative splicing, which exponentially increases the flow of biological information in cellular processes and can be an attractive therapeutic target. It is a crucial mechanism to increase genetic diversity. Disturbed alternative splicing is
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It has been estimated that 80% of the pre-mRNA undergoes alternative splicing, which exponentially increases the flow of biological information in cellular processes and can be an attractive therapeutic target. It is a crucial mechanism to increase genetic diversity. Disturbed alternative splicing is observed in many disorders, including neuromuscular diseases and carcinomas. Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. Homozygous deletion in 5q13 (the region coding for the motor neuron survival gene (SMN1)) is responsible for 95% of SMA cases. The nearly identical SMN2 gene does not compensate for SMN loss caused by SMN1 gene mutation due to different splicing of exon 7. A pathologically low level of survival motor neuron protein (SMN) causes degeneration of the anterior horn cells in the spinal cord with associated destruction of α-motor cells and manifested by muscle weakness and loss. Understanding the regulation of the SMN2 pre-mRNA splicing process has allowed for innovative treatment and the introduction of new medicines for SMA. After describing the concept of splicing modulation, this review will cover the progress achieved in this field, by highlighting the breakthrough accomplished recently for the treatment of SMA using the mechanism of alternative splicing.
Full article
(This article belongs to the Special Issue Alternative Splicing in Human Physiology and Disease)
Open AccessArticle
Three ParA Dimers Cooperatively Assemble on Type Ia Partition Promoters
Genes 2021, 12(9), 1345; https://doi.org/10.3390/genes12091345 - 28 Aug 2021
Abstract
Accurate DNA segregation is essential for faithful inheritance of genetic material. In bacteria, this process is mainly ensured by partition systems composed of two proteins, ParA and ParB, and a centromere site. Auto-regulation of Par operon expression is important for efficient partitioning and
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Accurate DNA segregation is essential for faithful inheritance of genetic material. In bacteria, this process is mainly ensured by partition systems composed of two proteins, ParA and ParB, and a centromere site. Auto-regulation of Par operon expression is important for efficient partitioning and is primarily mediated by ParA for type Ia plasmid partition systems. For the F-plasmid, four ParAF monomers were proposed to bind to four repeated sequences in the promoter region. By contrast, using quantitative surface-plasmon-resonance, we showed that three ParAF dimers bind to this region. We uncovered that one perfect inverted repeat (IR) motif, consisting of two hexamer sequences spaced by 28-bp, constitutes the primary ParAF DNA binding site. A similar but degenerated motif overlaps the former. ParAF binding to these motifs is well supported by biochemical and modeling analyses. Molecular dynamics simulations predict that the winged-HTH domain displays high flexibility, which may favor the cooperative ParA binding to the promoter. We propose that three ParAF dimers bind cooperatively to overlapping motifs, thus covering the promoter region. A similar organization is found on closely related and distant plasmid partition systems, suggesting that such promoter organization for auto-regulated Par operons is widespread and may have evolved from a common ancestor.
Full article
(This article belongs to the Special Issue Bacterial DNA Organization and Segregation)
Open AccessArticle
The Stress-Dependent Dynamics of Saccharomyces cerevisiae tRNA and rRNA Modification Profiles
Genes 2021, 12(9), 1344; https://doi.org/10.3390/genes12091344 - 28 Aug 2021
Abstract
RNAs are key players in the cell, and to fulfil their functions, they are enzymatically modified. These modifications have been found to be dynamic and dependent on internal and external factors, such as stress. In this study we used nucleic acid isotope labeling
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RNAs are key players in the cell, and to fulfil their functions, they are enzymatically modified. These modifications have been found to be dynamic and dependent on internal and external factors, such as stress. In this study we used nucleic acid isotope labeling coupled mass spectrometry (NAIL-MS) to address the question of which mechanisms allow the dynamic adaptation of RNA modifications during stress in the model organism S. cerevisiae. We found that both tRNA and rRNA transcription is stalled in yeast exposed to stressors such as H2O2, NaAsO2 or methyl methanesulfonate (MMS). From the absence of new transcripts, we concluded that most RNA modification profile changes observed to date are linked to changes happening on the pre-existing RNAs. We confirmed these changes, and we followed the fate of the pre-existing tRNAs and rRNAs during stress recovery. For MMS, we found previously described damage products in tRNA, and in addition, we found evidence for direct base methylation damage of 2′O-ribose methylated nucleosides in rRNA. While we found no evidence for increased RNA degradation after MMS exposure, we observed rapid loss of all methylation damages in all studied RNAs. With NAIL-MS we further established the modification speed in new tRNA and 18S and 25S rRNA from unstressed S. cerevisiae. During stress exposure, the placement of modifications was delayed overall. Only the tRNA modifications 1-methyladenosine and pseudouridine were incorporated as fast in stressed cells as in control cells. Similarly, 2′-O-methyladenosine in both 18S and 25S rRNA was unaffected by the stressor, but all other rRNA modifications were incorporated after a delay. In summary, we present mechanistic insights into stress-dependent RNA modification profiling in S. cerevisiae tRNA and rRNA.
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(This article belongs to the Special Issue Functions and Dynamics of RNA Modifications)
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Open AccessReview
Progress in Research on the Mechanisms Underlying Chloroplast-Involved Heat Tolerance in Plants
Genes 2021, 12(9), 1343; https://doi.org/10.3390/genes12091343 - 28 Aug 2021
Abstract
Global warming is a serious challenge plant production has to face. Heat stress not only affects plant growth and development but also reduces crop yield and quality. Studying the response mechanisms of plants to heat stress will help humans use these mechanisms to
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Global warming is a serious challenge plant production has to face. Heat stress not only affects plant growth and development but also reduces crop yield and quality. Studying the response mechanisms of plants to heat stress will help humans use these mechanisms to improve the heat tolerance of plants, thereby reducing the harm of global warming to plant production. Research on plant heat tolerance has gradually become a hotspot in plant molecular biology research in recent years. In view of the special role of chloroplasts in the response to heat stress in plants, this review is focusing on three perspectives related to chloroplasts and their function in the response of heat stress in plants: the role of chloroplasts in sensing high temperatures, the transmission of heat signals, and the improvement of heat tolerance in plants. We also present our views on the future direction of research on chloroplast related heat tolerance in plants.
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(This article belongs to the Section Genes & Environments)
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Genetic Diversity and Identification of Homozygosity-Rich Genomic Regions in Seven Italian Heritage Turkey (Meleagris gallopavo) Breeds
by
, , , , and
Genes 2021, 12(9), 1342; https://doi.org/10.3390/genes12091342 - 28 Aug 2021
Abstract
Italian autochthonous turkey breeds are an important reservoir of genetic biodiversity that should be maintained with an in vivo approach. The aim of this study, part of the TuBAvI national project on biodiversity, was to use run of homozygosity (ROH), together with others
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Italian autochthonous turkey breeds are an important reservoir of genetic biodiversity that should be maintained with an in vivo approach. The aim of this study, part of the TuBAvI national project on biodiversity, was to use run of homozygosity (ROH), together with others statistical approaches (e.g., Wright’s F-statistics, principal component analysis, ADMIXTURE analysis), to investigate the genomic diversity in several heritage turkey breeds. We performed a genome-wide characterization of ROH-rich regions in seven autochthonous turkey breeds, i.e., Brianzolo (Brzl), Bronzato Comune Italiano (BrCI), Bronzato dei Colli Euganei (CoEu), Parma e Piacenza (PrPc), Nero d’Italia (NeIt), Ermellinato di Rovigo (ErRo) and Romagnolo (Roma). ROHs were detected based on a 650K SNP genotyping. ROH_islands were identified as homozygous ROH regions shared by at least 75% of birds (within breed). Annotation of genes was performed with DAVID. The admixture analyses revealed that six breeds are unique populations while the Roma breed consists in an admixture of founder populations. Effective population size estimated on genomic data shows a numeric contraction. ROH_islands harbour genes that may be interesting for target selection in commercial populations also. Among them the PTGS2 and PLA2G4A genes on chr10 were related to reproduction efficiency. This is the first study mapping genetic variation in autochthonous turkey populations. Breeds were genetically different among them, with the Roma breed proving to be a mixture of the other breeds. The ROH_islands identified harboured genes peculiar to the selection that occurred in heritage breeds. Finally, this study releases previously undisclosed information on existing genetic variation in the turkey species.
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(This article belongs to the Special Issue Poultry Genetics, Breeding and Biotechnology)
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Open AccessReview
Lizards as Model Organisms of Sex Chromosome Evolution: What We Really Know from A Systematic Distribution of Available Data?
Genes 2021, 12(9), 1341; https://doi.org/10.3390/genes12091341 - 28 Aug 2021
Abstract
Lizards represent unique model organisms in the study of sex determination and sex chromosome evolution. Among tetrapods, they are characterized by an unparalleled diversity of sex determination systems, including temperature-dependent sex determination (TSD) and genetic sex determination (GSD) under either male or female
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Lizards represent unique model organisms in the study of sex determination and sex chromosome evolution. Among tetrapods, they are characterized by an unparalleled diversity of sex determination systems, including temperature-dependent sex determination (TSD) and genetic sex determination (GSD) under either male or female heterogamety. Sex chromosome systems are also extremely variable in lizards. They include simple (XY and ZW) and multiple (X1X2Y and Z1Z2W) sex chromosome systems and encompass all the different hypothesized stages of diversification of heterogametic chromosomes, from homomorphic to heteromorphic and completely heterochromatic sex chromosomes. The co-occurrence of TSD, GSD and different sex chromosome systems also characterizes different lizard taxa, which represent ideal models to study the emergence and the evolutionary drivers of sex reversal and sex chromosome turnover. In this review, we present a synthesis of general genome and karyotype features of non-snakes squamates and discuss the main theories and evidences on the evolution and diversification of their different sex determination and sex chromosome systems. We here provide a systematic assessment of the available data on lizard sex chromosome systems and an overview of the main cytogenetic and molecular methods used for their identification, using a qualitative and quantitative approach.
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(This article belongs to the Special Issue Sex Chromosome Evolution and Meiosis)
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Association Analysis of Polymorphic Variants of the BDNF Gene in Athletes
by
, , , , , , , , , , , , and
Genes 2021, 12(9), 1340; https://doi.org/10.3390/genes12091340 - 28 Aug 2021
Abstract
As BDNF is one of the group of neurotrophins highly influencing the processes happening in the brain, such as the processes of learning and personality creation, we decided to look closer at its genetic variations in association with the personality of a group
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As BDNF is one of the group of neurotrophins highly influencing the processes happening in the brain, such as the processes of learning and personality creation, we decided to look closer at its genetic variations in association with the personality of a group of athletes and their controls. The study group consisted of 305 volunteers: martial arts athletes (n = 153; mean age = 24.06) and healthy non-athletes as controls (n = 152; mean age = 22.23). Thirty-eight percent of the martial arts group achieved the championship level. Both the martial arts and control subjects were examined using the NEO Five-Factor Personality Inventory (NEO-FFI) and the State-Trait Anxiety Inventory (STAI) scales. The results of the NEO-FFI and STAI inventories were given as sten scores. The conversion of the raw score to the sten scale was performed according to Polish norms for adults. Genomic DNA was extracted from blood leukocytes and then genotyped using a PCR method for the following polymorphisms: BDNF rs10767664 and BDNF rs2030323. We observed statistical significance for both polymorphisms when comparing martial arts athletes with the control group in relation to the conscientiousness and extraversion scales. However, since few extant articles consider this association, our results still require further analysis, probably by considering a larger group.
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(This article belongs to the Special Issue Genetics and Genomics in Sport)
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