Genetic Diversity Research Articles

Dairy Cattle Reproduction, Production, and Disease Resistance in the Omics Era: Genome-Wide Selection Signatures Identify Candidate Genes in Sahiwal Cattle.

Climate emergency and ecological sustainability call for new ways of thinking livestock health, including the dairy cattle. This study unpacks the genetic diversity and selection sweeps of Sahiwal cattle in relation to adaptability, production, and disease resistance. Using nucleotide diversity (π) calculated from 10 kb windows across the genome with VCFtools, 716 regions of genetic diversity were identified across 29 chromosomes, and importantly, with chromosome 15 showing the highest density. A total of 92 quantitative trait loci (QTL) linked genes were analyzed, with chromosome 1 harboring the highest number. Trait association analysis using the Cattle QTL database showed that 14 genes were linked to production traits, 10 to reproduction traits, and 8 to disease susceptibility. Notable genes included CSMD2 and EFNA1, which influence milk production traits such as fat percentage and yield, and PCBP3 and SGCD, which affect reproductive traits. Additionally, the genes TBXAS1 and ASTN2 were associated with disease traits such as bovine respiratory disease and sole ulcers. Selection sweeps, identified using Tajima's D, revealed 728 sweeps across the genome, with chromosomes 6 and 8 showing the highest frequencies. These sweeps indicate regions under strong selective pressure, likely due to the breed's adaptation to arid environments and specific trait selection. The present study highlights how genetic diversity and selection sweeps contribute to Sahiwal cattle's adaptability, production efficiency, and disease resistance. The insights reported here provide a foundation for livestock health and targeted breeding strategies in the case of Sahiwal cattle under diverse ecological conditions such as tropical climate.

Genetic Diversity and Yield Traits Analysis Using Multivariate Approach in Bread Wheat Varieties

The present study was carried out at Nawabganj Farm, CSAUAT, Kanpur during Rabi season 2023-24. In this study, 24 wheat genotypes were tested using the complete randomized block design in five random plants per genotype for 19 traits. The harvest index had the highest coefficient of variability, while ear-bearing tillers per plant had the lowest. Results showed that PCV and GCV were high for Leaf area index and Flag leaf length. Additionally, all of the traits exhibit high heritability and some traits exhibit high genetic advance per cent of mean thus confirming additive gene action. Highly positive correlation was observed between grain yield per plant and days to 50% heading (0.50**), days to maturity (0.52**), ear weight (0.70**), spikelets per spike (0.73**), grains per spike (0.67**), biological yield per plant (0.73**) and harvest index (0.68**) indicating that the selection for these traits will increase yield. Eleven traits, including biological yield (0.7899), leaf area index (0.1094), harvest index (0.714), and grain width (0.0949) exerted positive direct effect on grain yield. The genotypes were grouped into five clusters using the Tocher's method and the distance between clusters IV and V was the highest, note genetic diversity high among these clusters, proof that hybridization should be productive to take advantage of heterosis and transgression segregation between these clusters. Principal component analysis (PCA) produced six principal components with eigenvalues > 1.0, which accounted for 83.3% of the total variation. PC1 contributed 28.7% of the variation with the highest eigenvalue (5.46). Traits associated with PC1 and PC2 are ideal candidates for selection.

Abstract 6963: The impact of aPKC inhibitors on PKC-ι/ζ; and connexin 43 in glioblastoma multiforme

Abstract Glioblastoma multiforme (GBM) is the most aggressive brain cancer in adults, arising from astrocytes. Its treatment is complicated by the blood-brain barrier, tumor infiltration, and genetic diversity, highlighting the urgent need for novel therapies. Our research group focuses on understanding the impact of ICA-S((-Amino-1-[(1R, 2S, 3R, 4R)-2, 3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl]-1H-imidazole-4-carboxamide), an atypical inhibitor of PKC-ι, and ζ ;-Stat (8-hydroxy-1, 3, 6-naphthalenetrisulfonic acid) inhibitor of PKC- ζ ; on GBM proliferation and invasion, as well as their effects on Connexin 43 (Cx43). PKC-ι / ζ ; plays a crucial role in GBM tumorigenesis by regulating cell proliferation and invasion. Its overexpression is directly influenced by phosphoinositide 3-kinase (PI3K). PKC-ι/ ζ ; and its upstream regulator, Src tyrosine kinase, regulate Cx 43, a gap junction protein that facilitates communication between astrocytic cancer cells and surrounding normal cells, thereby promoting cancer progression. The effects of aPKC inhibitors were assessed through proliferation assays on glioblastoma cell lines T98G and U87MG, revealing the impressive efficacy of both ICA-1S and ζ ;-Stat. ICA-1S achieved a statistically significant 50% reduction in T98G cell proliferation (p <0.001), while ζ ;-Stat resulted in a decrease of approximately 40% in proliferation within T98G cells (p< 0.001). Furthermore, ICA-1S also achieved around 40% reduction in proliferation in the U87 cell line (p< 0.001). Co-immunoprecipitation experiments provided evidence of the association between PKC-ι and Cx 43, as well as between PKC-ζ and Cx 43, in both cell lines. This suggests a direct interaction between these proteins, demonstrating their potential role in mediating cellular signaling and communication in GBM. Western blot analysis showed that ICA-1S downregulated PKC-ι and Cx43, while ζ ;-Stat downregulated PKC-ζ and its phosphorylation of Cx43, impacting the PI3K/AKT pathway. Immunofluorescence Analysis of T98G cells showed decreased Cx43 distribution following treatment, suggesting potential disruption of cell communication. Further analysis will investigate the effects of ICA-1S and ζ-Stat on the U87MG cell line, specifically examining the PI3K/AKT pathway using western blotting and immunofluorescence. Moreover, High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) will be essential for identifying phosphorylation sites directly impacted by aPKCs and Src in Cx 43. These innovative therapeutic strategies hold promise for overcoming chemical resistance challenges and may enhance patient survival outcomes. Citation Format: Grazielly Caroline Teodoro, Mildred Acevedo-Duncan. The impact of aPKC inhibitors on PKC-ι/ ζ ; and connexin 43 in glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6963.

Abstract 5481: A 3D bioprinted vascularized human tumor-on-a-Chip model for simultaneous evaluation of immunotherapeutic efficacy and safety

Abstract Immuno-oncology has revolutionized cancer treatment by harnessing the immune system to target tumors. However, developing effective therapies is challenging due to the complexity of the tumor microenvironment (TME), which influences therapy response, and toxicity risks like vascular injury and off-tumor effects. Traditional preclinical models fail to replicate human-specific immune responses and TME complexities, such as immune cell trafficking and tumor immune evasion. Additionally, current safety assessments for immunotherapies are inadequate in predicting systemic risks. These limitations highlight the need for more accurate, human-relevant tumor models. To address these challenges, we developed a 3D vascularized tumor-on-a-chip platform that incorporates key TME features for enhanced clinical relevance. Using 3D bioprinting, we integrated vascular structures with our human vascularized integrated organ system (h-VIOS™), enabling dynamic perfusion and simulating immune cell flow. The vasculature, endothelialized with primary human endothelial cells, forms a functional barrier expressing junctional markers and adhesion molecules, supporting immune cell interactions during T cell trafficking and tumor infiltration, while facilitating immunotherapy safety evaluation. Our model also integrates patient-derived tumor organoids that replicate key tumor characteristics, including heterogeneity and genetic diversity, and simulates TME interactions through co-culture with endothelial and immune cells. In a colorectal cancer model, we demonstrated chemokine-driven T cell infiltration from the endothelialized vasculature into the tumor, confirmed by confocal imaging and flow cytometry. We also modeled T cell responses to immune checkpoint inhibition with pembrolizumab, showing increased tumor killing, evidenced by elevated markers such as IFN-γ, Granzyme B, and cleaved-caspase 3. These results validate anti-PD-1 therapy in our model, highlighting its ability to capture T cell reactivation and tumor killing. In a TROP-2-expressing lung cancer model, we recapitulated the efficacy of the TROP-2 antibody-drug conjugate Sacituzumab govitecan, shown by increased cleaved-caspase 3 and reduced tumoroid viability. We also observed drug-induced vascular injury (DIVI) and off-tumor toxicity, evidenced by upregulation of inflammatory markers (ICAM-1, PECAM, P-selectin, IL-6, TNF-α) in endothelial cells. In conclusion, our 3D vascularized tumor-on-a-chip model outperforms traditional models by accurately replicating the TME and enabling the simultaneous assessment of drug-induced toxicities. This customizable platform facilitates mechanism-of-action studies and holds significant potential for personalized medicine, offering a powerful tool for advancing immuno-oncology research and improving therapeutic outcomes. Citation Format: Juliana Navarro-Yepes, Queeny Dasgupta, Purboja Purkayastha, Clara Erice, Carly Truong, Kim Phan, YongDuk Han, Michael Doerfert, Cassio Mello, Kevin Janson, Alma Antonio, Tracy Lin, Ameya Narkar, Sammy Datwani, SoonSeng Ng, Taci Pereira. A 3D bioprinted vascularized human tumor-on-a-Chip model for simultaneous evaluation of immunotherapeutic efficacy and safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5481.

The effects of agroforestry and conventional banana plantations on multiple dimensions of butterfly diversity in the Atlantic Forest

Abstract Environmental changes, particularly in agriculture, contribute significantly to biodiversity loss, with habitat fragmentation hindering dispersal and reducing biological diversity. Specific land uses can confine evolutionary groups to certain areas, decreasing local genetic and phylogenetic diversity but potentially increasing them at a larger spatial scale. Utilising genetic information at the population level, along with richness, phylogenetic and composition data at the community level, offers a comprehensive understanding of agriculture’s impact on biodiversity. In this study, we compared the effects of conventional and agroforestry banana plantations on butterflies’ dispersal and diversity relative to native forests. Analysing ddRAD genomic data from Heliconius ethilla narcaea at the population level and assessing richness, abundance, phylogenetic and species diversity of the Nymphalidae family at the community level, we found that agroforestry plantations exhibited the highest butterfly abundance and maintained the rarest genetic groups from H. ethilla narcaea. These genetic groups appeared in both native forests and agroforestry areas, more often in native forests, but were absent in conventional plantations despite evidence for extensive genetic dispersal. Regarding species composition, both banana plantations shared similar species but differed from the native forest, which contained a distinct and phylogenetically clustered group of species, possibly due to its unique microhabitat conditions and more complex structure. The presence of the rarest genetic groups in the population and the occurrence of distinct biological species emphasise the critical role of native forests within an anthropogenic landscape. Agroforestry demonstrates the potential to sustain biodiversity alongside food production.

Abstract 5931: Unraveling the genetic complexity of Ph-like ALL: development of a cost-effective diagnostic qPCR panel

Abstract Background: Advancements in high-throughput sequencing have significantly expanded our understanding of B-cell Acute Lymphoblastic Leukemia (B-ALL). In particular, whole-transcriptome sequencing (WTS) has facilitated the discovery of the Ph-like ALL subtype. However, clinical integration of WTS remains challenging due to high costs and lack of standardized workflows. Ph-like ALL is marked by genetic heterogeneity, including diverse fusions and mutations, which complicates its diagnosis and limits targeted therapeutic options. This genetic complexity correlates with poor prognosis, emphasizing the need for accessible and effective diagnostic approaches. Aim: To develop a cost-effective, qPCR-based diagnostic panel for its detection and classification in clinical settings. Methods: A cohort of 394 newly diagnosed B-ALL cases were analyzed using RT-PCR and FISH for initial genetic screening. WTS was employed for comprehensive fusion detection, mutation analysis, and subtype classification. Kaplan-Meier survival analysis was used to evaluate patient outcomes, and a qPCR-based likelihood scoring model was developed based on differential gene expression (DEGs) to identify Ph-like ALL. Results: Whole transcriptome sequencing revealed that 13.1% of the B-ALL cases have Ph-like phenotype, found in different age groups: 9.7% in pediatric patients (n=15), 20.5% in adolescents and young adults (AYA, n=8), and 50% in adults (n=3). Ph-like ALL cases predominantly exhibited fusions involving JAK-STAT pathway genes (n=10), ABL-class genes (n=9), or NTRK1 (n=1), in addition to a novel RUNX1::FGF13 fusion (n=2). Differentially expressed genes were tested for diagnostic potential, with 9 genes (FZH2, PON2, CA6, OLFML2A, BAALC, PRKCZ, ZFPM2, TCFL5 and ENPP2) demonstrating significant ROC (p<0.0001 and sensitivity and specificity >80%) curves in a discovery cohort (n=79). This likelihood model also effectively distinguished Ph-like ALL in a validation cohort (n=150). Additionally, survival analysis revealed significantly worse event-free survival (EFS) and overall survival (OS) in Ph-like ALL patients compared to non-Ph-like patients (EFS: 0% vs. 43.3%, HR 3.40, p=0.006; OS: 0% vs. 45.4%, HR 3.57, p=0.005). Conclusion: This study underscores the genetic diversity of Ph-like ALL. The poor prognosis of Ph-like ALL, marked by significantly reduced EFS and OS, highlights the need for targeted therapeutic approaches. The cost-effective qPCR-based diagnostic panel provides a promising tool for the early detection of Ph-like ALL, offering potential for improved patient outcomes through timely intervention. Citation Format: Anita Chopra, Jay Singh, Mercilena Benjamin, Avanish Pandey, Jayanth Kumar Palanichamy, Sameer Bakhshi, Deepam Pushpam, Akash Kumar Jha, Pranay Tanwar. Unraveling the genetic complexity of Ph-like ALL: development of a cost-effective diagnostic qPCR panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5931.

Building Biodiverse Urban Forests in the Post-Soviet City

This visual essay outlines how Ruderal, a studio based in Tbilisi, Georgia, has developed new approaches to urban forestry applicable to the legacy of Soviet-era forests. The collapse of the Georgian Soviet Socialist Republic and the resulting rapid privatization led to the reduction and degradation of Tbilisi’s public spaces. Ruderal’s approach to urban forestry is presented in three projects: the Mtatsminda Pilot Project (including Narikala Ridge), the Betania House Forest Garden, and the Arsenal Oasis Project. The projects illustrate how a new practice of urban forestry has grown from the limitations and opportunities of Tbilisi’s urban context. Ruderal’s practice pursues interventions at multiple scales along the following forestry principles: 1) grafting into baseline conditions; 2) utilising and expanding the ‘fertile section’; 3) incorporating genetic diversity and species competition.

Abstract 4073: Massively parallel barcoding as an alternative to genetic demultiplexing in large cohort scRNA-Seq studies

Abstract Single-cell RNA sequencing (scRNA-Seq) studies with large sample cohorts are expensive, and prone to batch effects. Genetic demultiplexing allows for pooling of distinct samples beforehand and then using bioinformatic tools post sequencing to identify individual samples based on their genetic makeup. This allows for super-loading conventional scRNA-seq runs while reducing costs and batch effects. However, these strategies often lead to up to 30% doublets and are limited by the quality of the reference genome used, and the genetic diversity of the input. Additional bulk sequencing and computational analyses add on costs and times to identify individual samples. This problem becomes more acute in diseases with heavy mutational burden like cancer - tumor-driven mutations might overshadow natural genetic variation between samples and extra sequencing and analyses might be warranted. Scale Bio has pioneered the use of massively parallelized barcoding and novel multiplexing strategies (ScalePlex) to boost throughput and circumvent the need for additional sample demultiplexing strategies to identify individual samples. Typical doublet rates in a Scale Bio scRNA-Seq library are around 5% and the protocol allows for simultaneous profiling of up to thousands of samples with Scaleplex, with significantly lower per sample inputs and no additional bulk sequencing required. Here we demonstrate the utility of the Scale Bio scRNA-Seq with and without Scaleplex in sample demultiplexing 12 samples from diseased and non-diseased individuals with similar genetic backgrounds when compared to super loading a conventional scRNA-seq run. Furthermore, we compare our data with current on market, publicly available computational tools for genetic demultiplexing with ScalePlex readouts as the ground truth. We observe low doublet rates in the Scale Bio data along with maximum utilization of possible sequencing reads, and clear, unambiguous sample identification when compared to conventional scRNA-seq techniques and analyses tools. Thus, the Scale Bio scRNA-seq platform offers a viable, low cost and effort platform for conventional genetic demultiplexing techniques with better resolution and higher sample multiplexing capacity. Furthermore, ScalePlex provides an alternative to easily, distinctly barcode and multiplex samples without genetic demultiplexing where researchers can gain the same benefits of reduced cost and batch effects while removing sample heterogeneity considerations and bioinformatics barrier of genetic demultiplexing. Citation Format: Sanika Khare, Dominic Skinner, Austin Holmes, Felix Schlesinger, Keith Jackson. Massively parallel barcoding as an alternative to genetic demultiplexing in large cohort scRNA-Seq studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4073.

Ecological characteristics of the coastal dune plant Artemisia stelleriana, along with genetic diversity of populations at Niigata Prefecture in Japan

AbstractCoastal dune plants play an important role in maintaining the stability of coastal dune areas. Artemisia stelleriana Besser. is a coastal dune plant with a northern distribution, and populations are scattered and isolated in Japan due to habitat loss, leading to its classification as an endangered species in several prefectures. However, very few ecological and genetic studies of A. stelleriana have been conducted worldwide. This study was performed to investigate the self‐compatibility, flower structure, and flowering phenology, seed thalassochory potential, and clonal propagation ability of A. stelleriana, along with the genetic diversity of four populations in Niigata Prefecture. Our results showed that A. stelleriana is self‐compatible, with a flower head composed of female and hermaphrodite florets that have overlapping flowering periods. The species also exhibits a relatively short seed floating period, which leads to limited seed dispersal by sea currents, and possesses a weak clonal structure due to its low ability for clonal propagation. In four populations in Niigata Prefecture, most individuals were fixed for a single homozygous genotype at all loci. Artemisia stelleriana is considered to have a flower structure suitable for self‐pollination, and it is assumed that this extremely low genetic diversity has been established through repeated self‐pollination within the population, with little gene flow between populations. Investigation of the genetic diversity and structure is necessary in the other four prefectures, where A. stelleriana is classified as an endangered species, in the future.

Establishment and characterization of NCC-PS2-C1: a novel cell line of high-grade pleomorphic spindle cell sarcoma, most consistent with myxofibrosarcoma.

Pleomorphic sarcoma (PS) is a heterogeneous group of malignant mesenchymal tumors that lack specific histological differentiation. PS is characterized by genetic instability and diversity and unique histological features such as pronounced morphologic pleomorphism. PS is one of the most common soft tissue sarcomas. Complete surgical resection remains the only curative treatment and is often combined with neoadjuvant radiotherapy. Effective systemic chemotherapy is yet to be established, and PS frequently recurs locally and metastasizes to the lungs. Patient-derived cancer cell lines are invaluable tools for basic and preclinical research for developing novel chemotherapies. Herein, we report a high-grade pleomorphic spindle cell sarcoma, most consistent with myxofibrosarcoma cell line, NCC-PS2-C1, which was derived from a primary tumor specimen. NCC-PS2-C1 cells exhibited a range of copy number alterations. This cell line demonstrated consistent proliferation, spheroid formation, and invasive capabilities in vitro. Drug screening using NCC-PS2-C1 cells revealed that cobimetinib, crenolanib, and ixazomib were effective against PS. In conclusion, we established NCC-PS2-C1 cells from primary tumors of PS. This cell line is a valuable resource for developing novel chemotherapies.

Assessment of Genetic Variability and Character Association and Path-Coefficient Analysis in Wheat (Triticum aestivum L.) under Timely Sown Irrigated Condition

Wheat (Triticum aestivum L. em Thell.), a key staple crop globally, contributes significantly to food security and nutrition by providing 20% of the world’s resources. This study aimed to evaluate the genetic variability, heritability, and path analysis of 105 wheat genotypes, including four checks, under timely sown irrigated conditions in Uttar Pradesh, India during the rabi season 2022-23. The experiment was conducted using an Augmented Block Design across seven blocks, assessing traits such as days to flowering, days to maturity, plant height, tillers per plant, spike length, spikelets per spike, peduncle length, grains per spike, 1000-grain weight, biological yield, harvest index, and grain yield per plant. The results revealed significant variation among genotypes for all traits. High heritability was observed for traits such as number of grains per spike (99.82%) and grain yield per plant (99.35%). Genetic advance was notably high for grain yield per plant (65.49%) and biological yield (61.52%). The phenotypic coefficient of variation (PCV) generally exceeded the genotypic coefficient of variation (GCV), indicating environmental influence on trait expression. Grain yield per plant showed strong positive correlations with biological yield, grains per spike, and other yield-related traits. Path coefficient analysis indicated that biological yield had the highest direct effect on grain yield. This study provides valuable insights into the genetic diversity and variability of wheat genotypes, essential for breeding programs aiming to improve yield and adaptability.

Genetic diversity, core collection construction and genotype–environment associations of Eucalyptus cloeziana germplasm based on EST-SSR markers

Genetic diversity, core collection construction and genotype–environment associations of Eucalyptus cloeziana germplasm based on EST-SSR markers

Recent habitat modification of a tropical dry forest hotspot drives population genetic divergence in the Mexican leaf frog: a landscape genetics approach.

Tropical dry forests (TDF) are among the ecosystems with the highest deforestation and transformation rates. Because of habitat loss and fragmentation, modified landscapes can impose resistance to the movement of individuals, with important genetic consequences. One of the most affected taxa due to habitat alteration are amphibians, which currently face extreme population declines globally. Here, we used single nucleotide polymorphisms (SNPs) to evaluate genetic diversity, genetic structure, and the effect of landscape elements on genetic connectivity of the Mexican tree frog (Agalychnis dacnicolor) in a TDF biodiversity hotspot in Mexico. We collected samples of 96 individuals from 16 sites located within fragmented areas of TDF and within continuous forest in the Chamela-Cuixmala region. Sampling sites from the fragmented forest showed slightly lower genetic diversity and effective population size compared to those in the continuous forest. We detected three admixed genetic groups, in which most of the sites within the fragmented forest were differentiated from the sites within continuous forest. Although these analyses suggest historical gene flow, we did not detect significant recent migration among the three genetic groups. While original vegetation (TDF + tropical evergreen forest), and in some areas, agriculture facilitated genetic connectivity, open-areas (grasslands + human settlements + exposed soil), and agriculture in other areas limited genetic connectivity in A. dacnicolor. This study helps to understand the factors shaping contemporary population divergence in highly modified complex landscapes, and highlights the importance to maintain connectivity in a rapidly changing ecosystem.

Whole-Genome Sequencing Unveils the Uniqueness of Yushu Yaks (Bos grunniens)

The Yushu yak is one of China’s distinctive yak breeds, primarily distributed in the Yushu Tibetan Autonomous Prefecture of Qinghai Province and its surrounding areas. Yushu yaks are not only economically and culturally significant but also play a crucial role in protecting the ecosystem of the Qinghai-Tibet Plateau and promoting sustainable development. However, there are no clear records regarding the ancestry, population structure, and unique traits of Yushu yaks. Therefore, this study conducted an analysis of genetic diversity, population structure, and selection signals in Yushu yak populations, aiming to provide references for the conservation and utilization of the breed genetic resources. The results of the analysis showed that the Yushu yak population has high genetic diversity and low inbreeding coefficients, indicating a stable genetic structure. Population structure analysis revealed that the Yushu yak lineage is unique, with limited gene flow between domestic and wild yaks. Functional enrichment analysis of positively selected genes in Yushu yaks indicated prominent selection features related to growth and development as well as energy metabolism. Additionally, we classified the Yushu yak breeding bulls into family lineages based on kinship, which is essential for improving the efficiency of utilizing genetic resources and scientifically managing the population.

Tradeoffs between proliferation and transmission in virus evolution– insights from evolutionary and functional analyses of SARS-CoV-2

To be successful, a virus must maintain high between-host transmissibility while also effectively adapting within hosts. The impact of these potentially conflicting demands on viral genetic diversity and adaptation remains largely unexplored. These modes of adaptation can induce uncorrelated selection, bring mutations that enhance certain fitness aspects at the expense of others to high freqency, and contribute to the maintenance of genetic variation. The vast wealth of SARS-CoV-2 genetic data gathered from within and across hosts offers an unparalleled opportunity to test the above hypothesis. By analyzing a large set of SARS-CoV-2 sequences (~ 2 million) collected from early 2020 to mid-2021, we found that high frequency mutations within hosts are sometimes detrimental during between-host transmission. This highlights potential inverse selection pressures within- versus between-hosts. We also identified a group of nonsynonymous changes likely maintained by pleiotropy, as their frequencies are significantly higher than neutral expectation, yet they have never experienced clonal expansion. Analyzing one such mutation, spike M1237I, reveals that spike I1237 boosts viral assembly but reduces in vitro transmission, highlighting its pleiotropic effect. Though they make up about 2% of total changes, these types of variants represent 37% of SARS-CoV-2 genetic diversity. These mutations are notably prevalent in the Omicron variant from late 2021, hinting that pleiotropy may promote positive epistasis and new successful variants. Estimates of viral population dynamics, such as population sizes and transmission bottlenecks, assume neutrality of within-host variation. Our demonstration that these changes may affect fitness calls into question the robustness of these estimates.

Molecular mapping of a novel locus S68 for intrasubspecific hybrid sterility in indica-indica hybrid

Oryza. sativa subsp. indica, a subspecies of Asian cultivated rice, plays a crucial role in global rice production, particularly in the utilization of hybrid vigor. However, the genetic basis of hybrid sterility among indica-indica intrasubspecific hybrids remains elusive, hindering the effective exploitation of heterosis in rice breeding programs. In this study, a near isogenic line (NIL) was developed using the indica variety Swarna as the donor parent and the indica variety IR64 as the recurrent parent. A novel locus, designated S68, responsible for intrasubspecific hybrid sterility was mapped to the region between RM14247 and RM3413 on the short arm of chromosome 3, spanning approximately 190 kb. S68 followed one-locus allelic interaction model. In IR64/NIL-S68 hybrids, the gametes from IR64 exhibit a transmission advantage, while those from Swarna are aborted in the heterozygote. This is the first hybrid sterile locus identified in indica-indica intrasubspecific hybrids, which enhances our understanding of the genetic mechanisms underlying intrasubspecific hybrid sterility and the genetic divergence within indica rice, thereby providing guidance for hybrid breeding programs within the indica subspecies.

Evidence for a Role of Extraintestinal Pathogenic Escherichia coli, Enterococcus faecalis and Streptococcus gallolyticus in the Aetiology of Exudative Cloacitis in the Critically Endangered Kākāpō (Strigops habroptilus).

The kākāpō is a critically endangered flightless parrot which suffers from exudative cloacitis, a debilitating disease resulting in inflammation of the vent margin or cloaca. Despite this disease emerging over 20 years ago, the cause of exudative cloacitis remains elusive. We used total RNA sequencing and metatranscriptomic analysis to characterise the infectome of lesions and cloacal swabs from nine kākāpō affected with exudative cloacitis, and compared this to cloacal swabs from 45 non-diseased kākāpō. We identified three bacterial species-Streptococcus gallolyticus, Enterococcus faecalis and Escherichia coli-as significantly more abundant in diseased kākāpō compared to healthy individuals. The genetic diversity observed in both S. gallolyticus and E. faecalis among diseased kākāpō suggests that these bacteria originate from exogenous sources rather than from kākāpō-to-kākāpō transmission. The presence of extraintestinal pathogenic E. coli (ExPEC)-associated virulence factors in the diseased kākāpō population suggests that E. coli may play a critical role in disease progression by facilitating iron acquisition and causing DNA damage in host cells, possibly in association with E. faecalis. No avian viral, fungal nor other parasitic species were identified. These results, combined with the consistent presence of one E. coli gnd sequence type across multiple diseased birds, suggest that this species may be the primary cause of exudative cloacitis. These findings shed light on possible causative agents of exudative cloacitis, and offer insights into the interplay of microbial factors influencing the disease.

Understanding genetic diversity and population structure of CIMMYT and IITA early maturing provitamin A maize (Zea mays L.) inbred lines using phenotypic traits and SNP markers for variable tolerance to drought and heat stress

Understanding genetic relationships of maize inbred lines before integrating them into a breeding program is crucial for optimizing heterosis. In this study we assessed the genetic diversity and population structure of 188 early maturing provitamin A maize inbred lines sourced from CIMMYT and IITA using 3.3 K SNPs markers and phenotypic traits data. The results showed highly significant statistical variability (p < 0.000) for key phenotypic traits such as, anthesis date (AD), anthesis-silking interval (ASI), senescence (SEN), ears per plant (EPP) and grain yield (GYD). Inbred lines DS19753, TZMI1989, DS197-206 and DS197-338 had high grain yield under drought and heat stress conditions whilst CML 486, DS197-308, DS197-185, and DS197-318 performed better under non-drought and heat stress conditions. The genetic diversity analysis revealed moderate genetic diversity (GD) of 0.24, and a polymorphic information content (PIC) of 0.20. A minor allele frequency (MAF) of 18% suggested relatively low genetic variation amongst the inbred lines whilst observed heterozygosity (Ho) of 0.02 and Fixation Index (F) of 0.90 indicated fixation of most loci in the inbred lines. Delta K was highest at K = 2 suggesting presence of two distinct genetic sub-populations. Analysis of Molecular Variance indicated that the estimated variance amongst the two populations (0.001) was minimal whilst most of the genetic variance occurs within populations (0.499). The phenotypic diversity revealed supported by genotypic variations among the assessed genotypes suggests a possibility of successful selection of superior drought and heat tolerant provitamin A maize inbred lines that can be used for developing hybrids.

Systematic analysis of population studies performed with the ForenSeq™ DNA Signature Prep kit.

Many forensic laboratories have conducted sequence-based population studies to support the integration of massively parallel sequencing (MPS). However, the data remain limited concerning African populations. MPS enhances allelic representation compared to CE methods. It is hypothesized that this increase will be more pronounced for African populations due to their greater genetic diversity. A systematic review and meta-analysis were conducted to compile data from population genetic studies using the ForenSeq™ DNA Signature Prep kit, frequently employed in forensic MPS population studies. The aim of the review was to gain insight into global forensic sequence-based population data, focusing on African and underrepresented populations. The search spanned three databases, resulting in 582 records, where 40 articles met inclusion criteria for the systematic review and 20 qualified for the meta-analysis. The meta-analysis aimed to quantify the increase in genetic variation in autosomal short tandem repeat (A-STR) markers using allele counts and random match probability (RMP). Most population studies were conducted in high-income countries (65%, 26/40), with none from Africa. Only 14 out of 40 studies included concordance data, with 13 of these reporting rates above 99%. The meta-analysis covered 35 population groups and found that of the 27 A-STR markers evaluated, mean allele counts increased by 53.08% from length-to-sequence-based analyses. African ancestry groups showed the highest increase in allele counts and the biggest reduction in RMP. Despite substantial genetic diversity in African populations, their representation in MPS studies is minimal. Addressing this gap is crucial to justify further research in African countries.

Phylogenomics and population genomics of Nothobranchius in lowland Tanzania: Species delimitation and comparative genetic structure.

Phylogenomics and population genomics of Nothobranchius in lowland Tanzania: Species delimitation and comparative genetic structure.