Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses. Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET). Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02). Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

On Protein Loops, Prior Molecular States and Common Ancestors of Life.

The principle of continuity demands the existence of prior molecular states and common ancestors responsible for extant macromolecular structure. Here, we focus on the emergence and evolution of loop prototypes - the elemental architects of protein domain structure. Phylogenomic reconstruction spanning superkingdoms and viruses generated an evolutionary chronology of prototypes with six distinct evolutionary phases defining a most parsimonious evolutionary progression of cellular life. Each phase was marked by strategic prototype accumulation shaping the structures and functions of common ancestors. The last universal common ancestor (LUCA) of cells and viruses and the last universal cellular ancestor (LUCellA) defined stem lines that were structurally and functionally complex. The evolutionary saga highlighted transformative forces. LUCA lacked biosynthetic ribosomal machinery, while the pivotal LUCellA lacked essential DNA biosynthesis and modern transcription. Early proteins therefore relied on RNA for genetic information storage but appeared initially decoupled from it, hinting at transformative shifts of genetic processing. Urancestral loop types suggest advanced folding designs were present at an early evolutionary stage. An exploration of loop geometric properties revealed gradual replacement of prototypes with α-helix and ß-strand bracing structures over time, paving the way for the dominance of other loop types. AlphFold2-generated atomic models of prototype accretion described patterns of fold emergence. Our findings favor a ?processual' model of evolving stem lines aligned with Woese's vision of a communal world. This model prompts discussing the 'problem of ancestors' and the challenges that lie ahead for research in taxonomy, evolution and complexity.

Seasonal effects decouple SARS-CoV-2 haplotypes worldwide.

Background: Variants of concern (VOCs) have been replacing each other during the still rampant COVID-19 pandemic. As a result, SARS-CoV-2 populations have evolved increasingly intricate constellations of mutations that often enhance transmissibility, disease severity, and other epidemiological characteristics. The origin and evolution of these constellations remain puzzling. Methods: Here we study the evolution of VOCs at the proteome level by analyzing about 12 million genomic sequences retrieved from GISAID on July 23, 2022. A total 183,276 mutations were identified and filtered with a relevancy heuristic. The prevalence of haplotypes and free-standing mutations was then tracked monthly in various latitude corridors of the world. Results: A chronology of 22 haplotypes defined three phases driven by protein flexibility-rigidity, environmental sensing, and immune escape. A network of haplotypes illustrated the recruitment and coalescence of mutations into major VOC constellations and seasonal effects of decoupling and loss. Protein interaction networks mediated by haplotypes predicted communications impacting the structure and function of proteins, showing the increasingly central role of molecular interactions involving the spike (S), nucleocapsid (N), and membrane (M) proteins. Haplotype markers either affected fusogenic regions while spreading along the sequence of the S-protein or clustered around binding domains. Modeling of protein structure with AlphaFold2 showed that VOC Omicron and one of its haplotypes were major contributors to the distortion of the M-protein endodomain, which behaves as a receptor of other structural proteins during virion assembly. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Conclusions: Our study uncovers seasonal patterns of emergence and diversification occurring amid a highly dynamic evolutionary landscape of bursts and waves. The mapping of genetically-linked mutations to structures that sense environmental change with powerful ab initio modeling tools demonstrates the potential of deep-learning for COVID-19 predictive intelligence and therapeutic intervention.

Recruitment: A Problem of Entangled Temporal Parts.

Recruitment is a pervasive activity of life that is at the center of novelty generation and persistence. Without recruitment, novelties cannot spread and biological systems cannot maintain identity through time. Here we explore the problem of identity and change unfolding in space and time. We illustrate recruitment operating at different timescales with metabolic networks, protein domain makeup, the functionome, and the rise of viral 'variants of concern' during the coronavirus disease 2019 (COVID-19) pandemic. We define persistence within a framework of fluxes of matter-energy and information and signal processing in response to internal and external challenges. A 'triangle of persistence' describing reuse, innovation and stasis defines a useful polytope in a phase space of trade-offs between economy, flexibility and robustness. We illustrate how the concept of temporal parts embraced by the perdurantist school provides a processual 4-dimensional 'worm' view of biology that is historical and atemporal. This view is made explicit with chronologies and evolving networks inferred with phylogenomic methodologies. Exploring the origin and evolution of the ribosome reveals recruitment of helical segments and/or large fragments of interacting rRNA molecules in a unification process of accretion that is counteracted by diversification. A biphasic (bow-tie) theory of module generation models this frustrated dynamics. Finally, we further elaborate on a theory of entanglement that takes advantage of the dimensionality reduction offered by holographic principles to propose that short and long-distance interactions are responsible for the increasingly granular and tangled structure of biological systems.

Mitonuclear incompatibility as a hidden driver behind the genome ancestry of African admixed cattle.

BACKGROUND: Africa is an important watershed in the genetic history of domestic cattle, as two lineages of modern cattle, Bos taurus and B. indicus, form distinct admixed cattle populations. Despite the predominant B. indicus nuclear ancestry of African admixed cattle, B. indicus mitochondria have not been found on the continent. This discrepancy between the mitochondrial and nuclear genomes has been previously hypothesized to be driven by male-biased introgression of Asian B. indicus into ancestral African B. taurus. Given that this hypothesis mandates extreme demographic assumptions relying on random genetic drift, we propose a novel hypothesis of selection induced by mitonuclear incompatibility and assess these hypotheses with regard to the current genomic status of African admixed cattle. RESULTS: By analyzing 494 mitochondrial and 235 nuclear genome sequences, we first confirmed the genotype discrepancy between mitochondrial and nuclear genome in African admixed cattle: the absence of B. indicus mitochondria and the predominant B. indicus autosomal ancestry. We applied approximate Bayesian computation (ABC) to assess the posterior probabilities of two selection hypotheses given this observation. The results of ABC indicated that the model assuming both male-biased B. indicus introgression and selection induced by mitonuclear incompatibility explains the current genomic discrepancy most accurately. Subsequently, we identified selection signatures at autosomal loci interacting with mitochondria that are responsible for integrity of the cellular respiration system. By contrast with B. indicus-enriched genome ancestry of African admixed cattle, local ancestries at these selection signatures were enriched with B. taurus alleles, concurring with the key expectation of selection induced by mitonuclear incompatibility. CONCLUSIONS: Our findings support the current genome status of African admixed cattle as a potential outcome of male-biased B. indicus introgression, where mitonuclear incompatibility exerted selection pressure against B. indicus mitochondria. This study provides a novel perspective on African cattle demography and supports the role of mitonuclear incompatibility in the hybridization of mammalian species.

The emergence of SARS-CoV-2 variants of concern in Australia by haplotype coalescence reveals a continental link to COVID-19 seasonality.

SARS-CoV-2 continues to evolve, even after implementation of public-wide vaccination, as can be observed by an increasing number of mutations over time. Compared to responses by the United States and European countries, the disease mitigation strategies employed by the Australian government have been swift and effective. This provides a unique opportunity to study the emergence of variants of concern (VOCs) at many latitude levels in a country that has been able to control infection for the majority of the pandemic. In the present study, we explored the occurrence and accumulation of major mutations typical of VOCs in different regions of Australia and the effects that latitude has on the establishment of VOC-induced disease. We also studied the constellation of mutations characteristic of VOCs to determine if the mutation sets acted as haplotypes. Our goal was to explore processes behind the emergence of VOCs as the viral disease progresses towards becoming endemic. Most reported COVID-19 cases were in largest cities located within a -30°S to - 50°S latitude corridor previously identified to be associated with seasonal behavior. Accumulation plots of individual amino acid variants of major VOCs showed that the first major haplotypes reported worldwide were also present in Australia. A classification of accumulation plots revealed the existence of 18 additional haplotypes associated with VOCs alpha, delta and omicron. Core mutant constellations for these VOCs and curve overlaps for variants in each set of haplotypes demonstrated significant decoupling patterns, suggesting processes of emergence. Finally, construction of a "haplotype network" that describes the viral population landscape of Australia throughout the COVID-19 pandemic revealed significant and unanticipated seasonal patterns of emergence and diversification. These results provide a unique window into our evolutionary understanding of a human pathogen of great significance. They may guide future research into mitigation and prediction strategies for future VOCs.

A Minimal Framework for Describing Living Systems: A Multi-Dimensional View of Life Across Scales.

The almost limitless complexity of biology has led to two general approaches to understanding biological phenomena. One approach is dominated by reductionism in which high-level phenomena of whole systems are viewed as emerging from relatively simple and generally understood interactions at a substantially lower level. Although this approach is theoretically general, it can become intractable in practice when attempting to simultaneously explain a wide range of systems. A second approach is for specialists to investigate biological phenomena within one of many different hierarchical levels of description that are separated to decouple from concerns at other levels. Although this approach reduces the explanatory burden on specialists that operate within each level, it also reduces integration from insights gained at other levels. Thus, as beneficial as these approaches have been, they limit the scope and integration of knowledge across scales of biological organization to the detriment of a truly synoptic view of life. The challenge is to find a theoretical and experimental framework that facilitates a broader understanding of the hierarchy of life-providing permeability for the exchange of ideas among disciplinary specialists without discounting the peculiarities that have come to define those disciplines. For this purpose, coarse-grained, scale-invariant properties, and resources need to be identified that describe the characteristic features of a living system at all spatiotemporal scales. The approach will be aided by a common vernacular that underscores the realities of biological connections across a wide range of scales. Therefore, in this vision paper, we propose a conceptual approach based on four identified resources-energy, conductance, storage, and information (ECSI)-to reintegrate biological studies with the aim of unifying life sciences under resource limitations. We argue that no functional description of a living system is complete without accounting for at least all four of these resources. Thus, making these resources explicit will help to identify commonalities to aid in transdisciplinary discourse as well as opportunities for integrating among the differently scoped areas of specialized inquiry. The proposed conceptual framework for living systems should be valid across all scales and may uncover potential limitations of existing hypotheses and help researchers develop new hypotheses addressing fundamental processes of life without having to resort to reductionism.

The seasonal behaviour of COVID-19 and its galectin-like culprit of the viral spike.

Seasonal behaviour is an attribute of many viral diseases. Like other 'winter' RNA viruses, infections caused by the causative agent of COVID-19, SARS-CoV-2, appear to exhibit significant seasonal changes. Here we discuss the seasonal behaviour of COVID-19, emerging viral phenotypes, viral evolution, and how the mutational landscape of the virus affects the seasonal attributes of the disease. We propose that the multiple seasonal drivers behind infectious disease spread (and the spread of COVID-19 specifically) are in 'trade-off' relationships and can be better described within a framework of a 'triangle of viral persistence' modulated by the environment, physiology, and behaviour. This 'trade-off' exists as one trait cannot increase without a decrease in another. We also propose that molecular components of the virus can act as sensors of environment and physiology, and could represent molecular culprits of seasonality. We searched for flexible protein structures capable of being modulated by the environment and identified a galectin-like fold within the N-terminal domain of the spike protein of SARS-CoV-2 as a potential candidate. Tracking the prevalence of mutations in this structure resulted in the identification of a hemisphere-dependent seasonal pattern driven by mutational bursts. We propose that the galectin-like structure is a frequent target of mutations because it helps the virus evade or modulate the physiological responses of the host to further its spread and survival. The flexible regions of the N-terminal domain should now become a focus for mitigation through vaccines and therapeutics and for prediction and informed public health decision making.

Emergence of Hierarchical Modularity in Evolving Networks Uncovered by Phylogenomic Analysis.

Networks describe how parts associate with each other to form integrated systems which often have modular and hierarchical structure. In biology, network growth involves two processes, one that unifies and the other that diversifies. Here, we propose a biphasic (bow-tie) theory of module emergence. In the first phase, parts are at first weakly linked and associate variously. As they diversify, they compete with each other and are often selected for performance. The emerging interactions constrain their structure and associations. This causes parts to self-organize into modules with tight linkage. In the second phase, variants of the modules diversify and become new parts for a new generative cycle of higher level organization. The paradigm predicts the rise of hierarchical modularity in evolving networks at different timescales and complexity levels. Remarkably, phylogenomic analyses uncover this emergence in the rewiring of metabolomic and transcriptome-informed metabolic networks, the nanosecond dynamics of proteins, and evolving networks of metabolism, elementary functionomes, and protein domain organization.

Microbial community and functions associated with digestion of algal polysaccharides in the visceral tract of Haliotis discus hannai: Insights from metagenome and metatranscriptome analysis.

Haliotis discus hannai, a species of Pacific abalone, is a highly valuable food source throughout Northeast Asia. As H. discus hannai primarily feed on brown algae and largely extract their energy from algal polysaccharides, understanding the mechanisms by which they digest algal polysaccharides is essential for elucidating their energy metabolism. Gut microbes, as well as the host animal, are involved in the process of polysaccharide degradation. To identify algal polysaccharide-digestion mechanisms and their origin, we analyzed the metagenome and metatranscriptome of abalone visceral extracts. Microbial communities were characterized using the 16S rRNA gene sequences in the metagenome and our results differed significantly from those of previous studies using traditional microbiological methods such as bacterial cultivation and cloning. A greater diversity of bacterial taxa was identified here than was previously identified using cultivation methods. Furthermore, the most abundant bacterial taxa also differed from previous studies, which is not common when comparing the results of bacterial culturing with those of molecular methodologies. Based on the metatranscriptome, overall functions were identified and additional analyses were performed on the coding sequences of algal polysaccharide-digestive enzymes, including alginate lyase. Results of the transcriptomic analyses suggest that alginate lyase in the visceral extracts of H. discus hannai was produced by the host itself, not by visceral bacteria. This is the first next-generation sequencing study performed on abalone to characterize the visceral microbiota and the source of the ability to digest algal polysaccharides by analyzing the metagenome and metatranscriptome together.

Evolution of macromolecular structure: a 'double tale' of biological accretion and diversification.

The evolution of structure in biology is driven by accretion and diversification. Accretion brings together disparate parts to form bigger wholes. Diversification provides opportunities for growth and innovation. Here, we review patterns and processes that are responsible for a 'double tale' of accretion and diversification at various levels of complexity, from proteins and nucleic acids to high-rise building structures in cities. Parts are at first weakly linked and associate variously. As they diversify, they compete with each other and are selected for performance. The emerging interactions constrain their structure and associations. This causes parts to self-organise into modules with tight linkage. In a second phase, variants of the modules evolve and become new parts for a new generative cycle of higher-level organisation. Evolutionary genomics and network biology support the 'double tale' of structural module creation and validate an evolutionary principle of maximum abundance that drives the gain and loss of modules.

Origin and spread of Thoroughbred racehorses inferred from complete mitochondrial genome sequences: Phylogenomic and Bayesian coalescent perspectives.

The Thoroughbred horse breed was developed primarily for racing, and has a significant contribution to the qualitative improvement of many other horse breeds. Despite the importance of Thoroughbred racehorses in historical, cultural, and economical viewpoints, there was no temporal and spatial dynamics of them using the mitogenome sequences. To explore this topic, the complete mitochondrial genome sequences of 14 Thoroughbreds and two Przewalski's horses were determined. These sequences were analyzed together along with 151 previously published horse mitochondrial genomes from a range of breeds across the globe using a Bayesian coalescent approach as well as Bayesian inference and maximum likelihood methods. The racing horses were revealed to have multiple maternal origins and to be closely related to horses from one Asian, two Middle Eastern, and five European breeds. Thoroughbred horse breed was not directly related to the Przewalski's horse which has been regarded as the closest taxon to the all domestic horses and the only true wild horse species left in the world. Our phylogenomic analyses also supported that there was no apparent correlation between geographic origin or breed and the evolution of global horses. The most recent common ancestor of the Thoroughbreds lived approximately 8,100-111,500 years ago, which was significantly younger than the most recent common ancestor of modern horses (0.7286 My). Bayesian skyline plot revealed that the population expansion of modern horses, including Thoroughbreds, occurred approximately 5,500-11,000 years ago, which coincide with the start of domestication. This is the first phylogenomic study on the Thoroughbred racehorse in association with its spatio-temporal dynamics. The database and genetic history information of Thoroughbred mitogenomes obtained from the present study provide useful information for future horse improvement projects, as well as for the study of horse genomics, conservation, and in association with its geographical distribution.

Genome sequencing and protein domain annotations of Korean Hanwoo cattle identify Hanwoo-specific immunity-related and other novel genes.

BACKGROUND: Identification of genetic mechanisms and idiosyncrasies at the breed-level can provide valuable information for potential use in evolutionary studies, medical applications, and breeding of selective traits. Here, we analyzed genomic data collected from 136 Korean Native cattle, known as Hanwoo, using advanced statistical methods. RESULTS: Results revealed Hanwoo-specific protein domains which were largely characterized by immunoglobulin function. Furthermore, domain interactions of novel Hanwoo-specific genes reveal additional links to immunity. Novel Hanwoo-specific genes linked to muscle and other functions were identified, including protein domains with functions related to energy, fat storage, and muscle function that may provide insight into the mechanisms behind Hanwoo cattle's uniquely high percentage of intramuscular fat and fat marbling. CONCLUSION: The identification of Hanwoo-specific genes linked to immunity are potentially useful for future medical research and selective breeding. The significant genomic variations identified here can crucially identify genetic novelties that are arising from useful adaptations. These results will allow future researchers to compare and classify breeds, identify important genetic markers, and develop breeding strategies to further improve significant traits.

Order and polarity in character state transformation models that root the tree of life.

Harish and Kurland recently compared two evolutionary models that root the tree of life. Both models make use of unordered phylogenetic characters. Here we show that they confused one of their models with models that use Wagner ordered characters. In addition, we also show that these Wagner characters should be polarized a posteriori with the generality criterion and not with external outgroup hypotheses. These facts question the rationale of their comparative phylogenomic exercise.

Artificial selection increased body weight but induced increase of runs of homozygosity in Hanwoo cattle.

Artificial selection has been demonstrated to have a rapid and significant effect on the phenotype and genome of an organism. However, most previous studies on artificial selection have focused solely on genomic sequences modified by artificial selection or genomic sequences associated with a specific trait. In this study, we generated whole genome sequencing data of 126 cattle under artificial selection, and 24,973,862 single nucleotide variants to investigate the relationship among artificial selection, genomic sequences and trait. Using runs of homozygosity detected by the variants, we showed increase of inbreeding for decades, and at the same time demonstrated a little influence of recent inbreeding on body weight. Also, we could identify ~0.2 Mb runs of homozygosity segment which may be created by recent artificial selection. This approach may aid in development of genetic markers directly influenced by artificial selection, and provide insight into the process of artificial selection.

Genome sequence of the Japanese oak silk moth, Antheraea yamamai: the first draft genome in the family Saturniidae.

Background: Antheraea yamamai, also known as the Japanese oak silk moth, is a wild species of silk moth. Silk produced by A. yamamai, referred to as tensan silk, shows different characteristics such as thickness, compressive elasticity, and chemical resistance compared with common silk produced from the domesticated silkworm, Bombyx mori. Its unique characteristics have led to its use in many research fields including biotechnology and medical science, and the scientific as well as economic importance of the wild silk moth continues to gradually increase. However, no genomic information for the wild silk moth, including A. yamamai, is currently available. Findings: In order to construct the A. yamamai genome, a total of 147G base pairs using Illumina and Pacbio sequencing platforms were generated, providing 210-fold coverage based on the 700-Mb estimated genome size of A. yamamai. The assembled genome of A. yamamai was 656 Mb (>2 kb) with 3675 scaffolds, and the N50 length of assembly was 739 Kb with a 34.07% GC ratio. Identified repeat elements covered 37.33% of the total genome, and the completeness of the constructed genome assembly was estimated to be 96.7% by Benchmarking Universal Single-Copy Orthologs v2 analysis. A total of 15 481 genes were identified using Evidence Modeler based on the gene prediction results obtained from 3 different methods (ab initio, RNA-seq-based, known-gene-based) and manual curation. Conclusions: Here we present the genome sequence of A. yamamai, the first genome sequence of the wild silk moth. These results provide valuable genomic information, which will help enrich our understanding of the molecular mechanisms relating to not only specific phenotypes such as wild silk itself but also the genomic evolution of Saturniidae.

Selective pressure on the protein-coding genes of the pufferfish is correlated with phenotypic traits.

The pufferfish accumulates neurotoxic tetrodotoxin in its body and inflates by filling its stomach with water. These traits are unique to this species, and may be a result of adaptation post-divergence of Tetraodontidae. However, evolution of the protein-coding genes in the pufferfish has not yet been well elucidated. Detection of positive selection on these genes can help us understand the mechanisms associated with functional evolution. We downloaded well-annotated gene information of two pufferfish species, Takifugu rubripes and Tetraodon nigroviridis, from the public ENSEMBL database. In order to detect selective pressure on protein-coding sequences, we performed dN/dS estimation using codeml within the PAML software package. We selected one to one orthologous genes among seven fish species (Gasterosteus aculeatus, Oryzias latipes, Poecilia formosa, Takifugu rubripes, Tetraodon nigroviridis, and Xiphophorus maculatus). Results of dN/dS analysis on orthologous genes indicate that pufferfish showed high non-synonymous substitution rate for positively selected genes, and the evolutionary rate was faster during the diversification of two pufferfishes after divergence. Additionally, a candidate mechanism for regulation of neuro-toxicity of tetrodotoxin was identified from functional annotation of positively selected genes. These results support positive selection on protein-coding genes of the pufferfish with the acquisition of specific phenotypic traits.

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance.

As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study.

Comparative Genomic Analysis of Lactobacillus plantarum GB-LP1 Isolated from Traditional Korean Fermented Food.

As probiotics play an important role in maintaining a healthy gut flora environment through antitoxin activity and inhibition of pathogen colonization, they have been of interest to the medical research community for quite some time now. Probiotic bacteria such as Lactobacillus plantarum, which can be found in fermented food, are of particular interest given their easy accessibility. We performed whole-genome sequencing and genomic analysis on a GB-LP1 strain of L. plantarum isolated from Korean traditional fermented food; this strain is well known for its functions in immune response, suppression of pathogen growth, and antitoxin effects. The complete genome sequence of GB-LP1 is a single chromosome of 3,040,388 bp with 2,899 predicted open reading frames. Genomic analysis of GB-LP1 revealed two CRISPR regions and genes showing accelerated evolution, which may have antibiotic and antitoxin functions. The aim of the present study was to predict strain specific-genomic characteristics and assess the potential of this new strain as lactic acid bacteria at the genomic level using in silico analysis. These results provide insight into the L. plantarum species as well as confirm the possibility of its utility as a candidate probiotic.