Population Bottlenecks Research Articles

Population structure and genetic diversity in males of the autochthonous Busha cattle in Croatia

Busha is recognized as the most numerous autochthonous cattle breed in Croatia. In small populations, using the same sire repeatedly can increase inbreeding rates. This can lead to fewer high-quality, and high inbred breeding sires over time. Genealogical records of the Busha cattle breed registered from 1987 to 2022 were used to investigate the population structure and the genetic variability of the male individuals. The dataset included 10,411 animals, of which 3,962 were males. The average equivalent complete generation reached 2.92 in the total population and 3.05 in the reference population, when considering only living animals. The average inbreeding coefficient in the male population was 1.59%. Over the studied period, inbreeding rose to an average value of 2.07% in the last birth year cohort (2017-2022). The unequal contribution of the effective number of founders indicates the more frequent use of particular breeding sire lines. Nevertheless, despite the controlled inbreeding rate observed among breeding sires, and the absence of any evident population bottleneck, our study highlighted the need for breeding strategies to optimize the contribution of breeding animals in the next generations to ensure long-term conservation of the Busha cattle breed.

Molecular Assessment of Genetic Diversity and Bottleneck in Hair Goat Reared in Türkiye

Objective: Being the most preferred and geographically distributed in Türkiye, the Hair goat was screened at a molecular level to evaluate genetic diversity and population structure via microsatellite DNA markers. This paper also aimed to investigate the effects of genetic bottleneck to evaluate whether the Hair goat has maintained its effective population size in recent past. Material and Methods: A total of 411 Hair goats were sampled from farms participating in the "Hair Goat Breeding" project, initiated by the General Directorate of Agricultural Research and Policies in Aydın and Denizli provinces. Sampled animals were genotyped with 18 microsatellite loci to assess genetic diversity, population structure, and genetic bottleneck. Results: A total of 341 different alleles were observed across 18 microsatellite loci in which the highest number of alleles (26) and effective alleles (10.18) were detected in INRA005 and HSC loci, respectively. The average observed heterozygosity (0.73) was lower than the expected value (0.83), whereas all loci turned out to be highly informative (PIC>0.50). Factorial correspondence analysis separated animals into two groups, while a genetic admixture was detected between these groups. STRUCTURE analysis, on the other hand, confirmed that 411 animals were derived from three ancestral populations in which the third group is drawn due to admixed individuals. The Wilcoxon test and mode-shift indicator detected a lack of genetic bottleneck indicating that Hair goats reared in Türkiye have maintained their effective population size in recent past. Conclusion: This study validates that used microsatellite markers are highly polymorphic and could be utilized for revealing genetic diversity in different local goat breeds. The findings recovered in this study could be integrated into breeding and conservation programs, while further studies should adopt SNP array technologies and next-generation sequencing platforms to reveal deeper knowledge about the genetic diversity and population structure of Anatolian goat breeds.

Conserved Evolutionary Trajectory Can Be Perturbed to Prevent Resistance Evolution under Norfloxacin Pressure by Forcing Mycobacterium smegmatis on Alternate Evolutionary Paths.

Antibiotic resistance is a pressing health issue, with the emergence of resistance in bacteria outcompeting the discovery of novel drug candidates. While many studies have used Adaptive Laboratory Evolution (ALE) to understand the determinants of resistance, the influence of the drug dosing profile on the evolutionary trajectory remains understudied. In this study, we employed ALE on Mycobacterium smegmatis exposed to various concentrations of Norfloxacin using both cyclic constant and stepwise increasing drug dosages to examine their impact on the resistance mechanisms selected. Mutations in an efflux pump regulator, LfrR, were found in all of the evolved populations irrespective of the drug profile and population bottleneck, indicating a conserved efflux-based resistance mechanism. This mutation appeared early in the evolutionary trajectory, providing low-level resistance when present alone, with a further increase in resistance resulting from successive accumulation of other mutations. Notably, drug target mutations, similar to those observed in clinical isolates, were only seen above a threshold of greater than 4× the minimum inhibitory concentration (MIC). A combination of three mutations in the genes, lfrR, MSMEG_1959, and MSMEG_5045, was conserved across multiple lineages, leading to high-level resistance and preceding the appearance of drug target mutations. Interestingly, in populations evolved from parental strains lacking the lfrA efflux pump, the primary target of the lfrR regulator, no lfrR gene mutations are selected. Furthermore, evolutional trajectories originating from the ΔlfrA strain displayed early arrest in some lineages and the absence of target gene mutations in those that evolved, albeit delayed. Thus, blocking or inhibiting the expression of efflux pumps can arrest or delay the fixation of drug target mutations, potentially limiting the maximum attainable resistance levels.

Genetic variability and population genetic structure in the Caucasian Parsley Frog, Pelodytes caucasicus (Boulenger, 1896) based on microsatellite markers

The Caucasian Parsley Frog, Pelodytes caucasicus (Boulenger, 1896), is endemic to Caucasia, and its population is decreasing. Here, we present information on the genetic structure and diversity of populations from four provinces of Türkiye (Giresun, Trabzon, Rize, and Artvin) using microsatellite markers. Despite their small geographic range, the species’ populations showed moderate genetic differentiation, which could be a result of rapid genetic drift. Our results show that Trabzon and Giresun populations are genetically different from those of Rize and Artvin. We found considerably low genetic diversity in Artvin, Trabzon, and Giresun populations. The inbreeding co-efficient is also high in those localities (HO<HE). Despite low genetic diversity and a high inbreeding coefficient, we could not find any sign of a genetic bottleneck.

Low genetic differentiation despite high habitat fragmentation in an endemic and endangered species of Iridaceae from South America: implications for conservation

Abstract To conserve threatened species effectively, it is crucial to map the genetic variation of the remaining populations. Thus, using 15 microsatellites markers, from which 10 were specially developed for this study, we investigated genetic structure and gene flow patterns of Herbertia zebrina Deble, a critically endangered species endemic from grasslands of southern Brazil. We also investigated the degree of habitat fragmentation and the impacts on levels of genetic diversity, mating system and pollinators of the species. STRUCTURE and discriminant analysis of principal components identified the existence of three genetic clusters. Populations were not isolated by distance, and genetic differentiation among populations was low (7.0%). Migration rates were also low, but no evidence of genetic bottlenecks was found. However, effective population-scaled mutation rates (Θ) were &amp;lt; 1, suggesting that populations could be experiencing genetic drift, but the reason remains unknown. The results indicate that measurements of habitat fragmentation were not significantly correlated with genetic diversity estimates, which tend to increase with fragment size. H. zebrina was identified as an outcrossing species and specialized pollinators, such as Chalepogenus goeldianus and Lanthanomelissa betinae were rarely observed. Our findings suggest that genetic differentiation across multiple populations within the entire geographic distribution of H. zebrina is very low and populations may struggle to adapt to the current environmental and pollination changes. However, habitat fragmentation is still too recent to detect significant impacts on the levels of genetic variation. Thus, conservation plans are necessary to avoid further declines of this species.

Genomic stasis over millions of years in subseafloor sediment.

One of the significant challenges in microbiology is to understand the extent and mechanisms of evolution within life beneath the surface of the Earth. The population bottleneck that microbes in deep marine sediment experience implies that mutational and population genetic forces could lead to higher levels of relaxed selection and an increase in pseudogenes. To investigate this hypothesis, a group of Thalassospira strains were isolated from subseafloor sediment that is 3 to 6 million years old, as reported by Orsi and colleagues in 2021. These isolates, representing lineages that have been buried for millions of years, offer an excellent opportunity to study the evolution of life beneath the seafloor over a long period. The existence of closely related strains from environments on the surface of the Earth enabled us to examine the impact of selection within each group. We discovered that isolates from beneath the seafloor show lineage-specific similarities to Thalassospira from the surface world, both in the overall intensity of selection on the genome and in the specific genes affected by mutation. We found no signs of increased relaxed selection or other notable genomic changesin the genomes of the Thalassospira isolates from beneath the seafloor, suggesting that these subseafloor isolates were awakened from a million-year near-stasis. The unique genomic characteristics of each Thalassospira lineage from beneath the seafloor must then reflect genetic changes that surface-inhabiting decendants acquired in the past 3-6 million years. Remarkably, Thalassospira lineages beneath the surface appear to have stably maintained their genomes in the midst of metabolic dormancy and extremely long generation times.

Single-nucleotide polymorphisms and copy number variations drive adaptive evolution to freezing stress in a subtropical evergreen broad-leaved tree: Hexaploid wild Camellia oleifera

Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress, while hexaploid wild Camellia oleifera shows strong freezing tolerance. As a valuable genetic resource of woody oil crop C. oleifera, wild C. oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress. Here, 47 wild C. oleifera from 11 natural distribution sites in China and 4 relative species of C. oleifera were selected for genome sequencing. “Min Temperature of Coldest Month” (BIO6) had the highest comprehensive contribution to wild C. oleifera distribution. The population genetic structure of wild C. oleifera could be divided into two groups: in cold winter (BIO6 ≤ 0 °C) and warm winter (BIO6 > 0 °C) areas. Wild C. oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower Ne than those in warm winter areas. 155 single-nucleotide polymorphisms (SNPs) were significantly correlated with the key bioclimatic variables (106 SNPs significantly correlated with BIO6). Twenty key SNPs and 15 key copy number variation regions (CNVRs) were found with genotype differentiation > 50% between the two groups of wild C. oleifera. Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance, and they were also found within a CNVR suggesting interactions between them. Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress. The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.

Population genomics of the endangered freshwater mussel, Arcidens wheeleri (Unionoidea: Unionidae: Anodontini), in the Little River, Arkansas, USA

ABSTRACT North America is a hotspot of freshwater mussel diversity. However, over the last century, many anthropogenic stressors have led to substantial declines in freshwater mussels of the families Unionidae and Margaritiferidae in North America. Conserving the remaining mussel fauna is a priority, as they play an integral role in freshwater ecosystems. The Little River in Arkansas is home to one of the last remaining populations of the federally endangered freshwater mussel, Arcidens wheeleri (Unionidae: Anodontini). Population dynamics information is lacking for A. wheeleri, and no population genetics study has been conducted on this species. A greater understanding of the genetic diversity within a population can serve as a benchmark for developing an effective management plan. We sampled A. wheeleri from three locations in the Little River. Genomic data were generated with a single-enzyme restriction-site-associated DNA sequencing approach to assess genetic diversity and structure of A. wheeleri in the Little River. Genetic structure analyses indicated one genetic population among the three locations, with limited, fine-scale subpopulation structure. Observed heterozygosity values were considerably lower than expected heterozygosity values, with Ho = 0.14 and He = 0.22, likely indicating a genetic bottleneck. Demographic analysis of the Little River population of A. wheeleri also suggests a historical bottleneck. Furthermore, a high inbreeding coefficient (FIS = 0.33) indicates A. wheeleri in the Little River is losing genetic diversity. Data generated indicate considerable risk of extirpation for A. wheeleri from the Little River and should serve as a baseline for future monitoring. Given its high risk of extinction, we recommend increased study of A. wheeleri across its range and on-the-ground conservation actions that include habitat protection and restoration, which are the only options until a successful host fish and protocols are identified for propagation.

Using Runs of Homozygosity and Machine Learning to Disentangle Sources of Inbreeding and Infer Self-Fertilization Rates.

Runs of homozygosity (ROHs) are indicative of elevated homozygosity and inbreeding due to mating of closely related individuals. Self-fertilization can be a major source of inbreeding which elevates genome-wide homozygosity and thus should also create long ROHs. While ROHs are frequently used to understand inbreeding in the context of conservation and selective breeding, as well as for consanguinity of populations and their demographic history, it remains unclear how ROH characteristics are altered by selfing and if this confounds expected signatures of inbreeding due to demographic change. Using simulations, we study the impact of the mode of reproduction and demographic history on ROHs. We apply random forests to identify unique characteristics of ROHs, indicative of different sources of inbreeding. We pinpoint distinct features of ROHs that can be used to better characterize the type of inbreeding the population was subjected to and to predict outcrossing rates and complex demographic histories. Using additional simulations and four empirical datasets, two from highly selfing species and two from mixed-maters, we predict the selfing rate and validate our estimations. We find that self-fertilization rates are successfully identified even with complex demography. Population genetic summary statistics improve algorithm accuracy particularly in the presence of additional inbreeding, e.g. from population bottlenecks. Our findings highlight the importance of ROHs in disentangling confounding factors related to various sources of inbreeding and demonstrate situations where such sources cannot be differentiated. Additionally, our random forest models provide a novel tool to the community for inferring selfing rates using genomic data.

Slow Hot-Exciton Cooling and Enhanced Interparticle Excitonic Coupling in HgTe Quantum Dots.

Rapid hot-carrier/exciton cooling constitutes a major loss channel for photovoltaic efficiency. How to decelerate the hot-carrier/exciton relaxation remains a crux for achieving high-performance photovoltaic devices. Here, we demonstrate slow hot-exciton cooling that can be extended to hundreds of picoseconds in colloidal HgTe quantum dots (QDs). The energy loss rate is 1 order of magnitude smaller than bulk inorganic semiconductors, mediated by phonon bottleneck and interband biexciton Auger recombination (BAR) effects, which are both augmented at reduced QD sizes. The two effects are competitive with the emergence of multiple exciton generation. Intriguingly, BAR dominates even under low excitation fluences with a decrease in interparticle distance. Both experimental evidence and numerical evidence reveal that such efficient BAR derives from the tunneling-mediated interparticle excitonic coupling induced by wave function overlap between neighboring HgTe QDs in films. Thus, our study unveils the potential for realizing efficient hot-carrier/exciton solar cells based on HgTe QDs. Fundamentally, we reveal that the delocalized nature of quantum-confined wave function intensifies BAR. The interparticle excitonic coupling may cast light on the development of next-generation photoelectronic materials, which can retain the size-tunable confinement of colloidal semiconductor QDs while simultaneously maintaining high mobilities and conductivities typical for bulk semiconductor materials.

A new lysine biosynthetic enzyme from a bacterial endosymbiont shaped by genetic drift and genome reduction.

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid-a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyzes the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased ~2-fold in the insect host compared to in planta. CLsoDHDPS has decreased thermal stability and increased aggregation propensity, implying mutations have destabilized the enzyme but are compensated for through elevated chaperone expression and a stabilized oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is to date unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study suggests the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary associations. We propose that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.

Elucidating population structure and genetic diversity of intercross sheep through pedigree analysis

The aim of this study was to assess the population structure and genetic diversity along with determining the accuracy of ongoing selection program in a closed flock of Intercross sheep through pedigree analysis. The pedigree records of 2245 animals maintained at CSWRI-NTRS, Garsa, Kullu during the period from 2012 to 2023 were utilized to calculate the genealogical information, genetic conservation index and other parameters based on gene origin probabilities. Lambs born during 2020 and 2023 were considered as reference population. ENDOG version 4.8 software package was used for pedigree analysis. Analysis revealed that the mean generation interval for the reference population was 3.20 years with a longer interval in dam-offspring pathways relative to sire-offspring pathways. Average inbreeding coefficients for whole and reference population were 0.21 and 0.49 % and corresponding average relatedness was 1.24 and 1.72 %, respectively. The average maximum, equivalent and completed generations were 2.50, 1.96 and 1.63 with 0.12 %, 0.17 % and 0.20 % increase in inbreeding coefficient, respectively. This resultant effective population size estimated using individual increase in inbreeding was 156.52. Effective numbers of founders (fe) and ancestors (fa) was 68 and 61, respectively for reference population with a ratio of 1.11, indicating occurrence of minor effects of bottleneck in the flock. The genetic contribution of most influent ancestors contributing 50 % of the gene pool was only 23. The estimated founder genome (fg) and non-founder genome (fng) were 35.87 and 75.91, respectively in the present population. The estimate for fg/fa ratio was 0.59 which explained that 59 % of the original genetic diversity is exit in the reference population. Genetic conservation index (GCI) ranged from 1 % to 20.28 % with a mean value of 4.91 %. Overall, males recorded a slightly higher GCI than females, i.e., 5.23 vs 4.65 %, respectively. The results revealed that, the population has augmented genetic diversity and low level of inbreeding. Small fraction of genetic diversity was vanished due to unequal contribution of founders and minor bottleneck effects occurred due to disproportionate contribution of breeding animals to gene pool of population. Use of a sufficient number of breeding rams and optimum contribution selection (OCS) is recommended to maintain the genetic diversity as well as enhancing production potential in this population.

Genetic diversity and population structure of Bellamya purificata in Guangxi.

Bellamya purificata is an important medicinal value and economically farmed species in China. However, because little is known about the genetic characteristics of this species, the utilization of high-quality germplasm resources is hindered. The study examined the genetic differentiation between, and the structure of 12 B. purificata populations in Guangxi using 7 microsatellite DNA markers. High genetic diversity occurred in each population, with mean observed heterozygosity 0.655 and a mean expected heterozygosity 0.832. Analysis of molecular variance reveals genetic diversity to be greater within (95.2%) than among populations (4.8%). Genetic differentiation between populations is weak (Fst = 0.048, P < 0.001), with mixing of genetic clusters prevalent at the level of the individual. Genetic flow exists between populations (Nm = 3.084-11.778), with Longshui and Guilin populations exchanging frequently. A Mantel test reveals a low correlation between geographic and genetic distances (r = 0.2482, P < 0.071), suggesting that dispersal between neighboring populations facilitates population exchange. No significant heterozygosity excess was observed for any population (P > 0.05), indicating a lack of recent genetic bottlenecks. The results provide important genetic information for B. purificata, and data for potential germplasm discovery and aquaculture development.

Temporal Changes in Geographic Range and Population Size of the Santa Cruz Black Salamander

Abstract The Santa Cruz black salamander Aneides niger is a priority 3 California species of special concern with a restricted geographic range confined to the Santa Cruz Mountains. Anecdotal observations suggest that the species was relatively abundant in the early 1900s, but it has become more difficult to find in the past few decades. To better understand if the species has undergone population size fluctuations, we analyzed mitochondrial and nuclear sequence data to examine levels of genetic variation and phylogeographic structure, and test for signatures of population size change. We then reconstructed the climatic suitability for the species to 1) determine if past climate fluctuations could have influenced range size and genetic diversity, and 2) estimate the effects of future climate change on geographic range suitability as a proxy for possible future population size change. Genetic analyses detected low levels of genetic variation and a general lack of genetic structuring, suggesting a recent genetic bottleneck. While neutrality tests of individual loci were nonsignificant, skyline plot and isolation-with-migration analyses detected a relatively recent reduction in population size. Interpretation of these genetic results should consider the limited number of localities and individuals sampled for this species. Climatic suitability for Santa Cruz black salamanders was much lower during the last glacial maximum, which could be the cause of the detected historical change in population size. Future projections of climatic suitability under a high-emission scenario suggest a dramatic geographic range restriction to coastal areas. These projections highlight the need for the protection of coastal habitat patches to preserve existing coastal populations, and to maintain connectivity between coastal and inland habitats to allow the westward movement of populations and genes in response to climate change.

Suppressing internet bottleneck with Kudryashov’s extended version of self-phase modulation and fractional temporal evolution

AbstractThe current paper employs Kudryashov’s approach to suppress Internet bottleneck effect for the model with factional temporal evolution, linear chromatic dispersion and Kudryahov’s proposed form of extended self-phase modulation with power-law embedded in it. Kudryasov’s approach to integration yielded soliton solutions that is used to transmit solitons across intercontinental distances with a controlled speed which can regulate the internet traffic flow.

Room temperature thermal rectification in suspended asymmetric graphene ribbon

Thermal rectifiers are essential in optimizing heat dissipation in solid-state devices to enhance energy efficiency, reliability, and overall performance. In this study, we experimentally investigate the thermal rectification phenomenon in suspended asymmetric graphene ribbons (GRs). The asymmetry within the graphene is introduced by incorporating periodic parallel nanoribbons on one side of the GR while maintaining the other side in a pristine form. Our findings reveal a substantial thermal rectification effect in these asymmetric graphene devices, reaching up to 45% at room temperature and increasing further at lower environmental temperatures. This effect is attributed to a significant thermal conductivity contrast between pristine graphene and nanoribbon graphene within the asymmetric structure. We observe that the incorporation of nanoribbons leads to a notable reduction in thermal conductivity, primarily due to phonon scattering and bottleneck effects near the nanoribbon edges. These findings suggest that graphene structures exhibiting asymmetry, facilitated by parallel nanoribbons, hold promise for effective heat management at the nanoscale level and the development of practical phononic devices.

The jacktree genome and population genomics provides insights for the mechanisms of the germination obstacle and the conservation of endangered ornamental plants.

Sinojackia Hu represents the first woody genus described by Chinese botanists, with all species classified as endangered ornamental plants endemic to China. Their characteristic spindle-shaped fruits confer high ornamental value to the plants, making them favored in gardens and parks. Nevertheless, the fruits likely pose a germination obstacle, contributing to the endangered status of this lineage. Here we report the chromosome-scale genome of S. xylocarpa, and explore the mechanisms underlying its endangered status, as well as its population dynamics throughout evolution. Population genomic analysis has indicated that S. xylocarpa experienced a bottleneck effect following the recent glacial period, leading to a continuous population reduction. Examination of the pericarp composition across six stages of fruit development revealed a consistent increase in the accumulation of lignin and fiber content, responsible for the sturdiness of mature fruits' pericarps. At molecular level, enhanced gene expression in the biosynthesis of lignin, cellulose and hemicellulose was detected in pericarps. Therefore, we conclude that the highly lignified and fibrotic pericarps of S. xylocarpa, which inhibit its seed germination, should be its threatening mechanism, thus proposing corresponding strategies for improved conservation and restoration. This study serves as a seminal contribution to conservation biology, offering valuable insights for the study of other endangered ornamental plants.

Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning

The synthesis of steroids is challenging through multistep steroidal core modifications with high site-selectivity and productivity. In this work, a novel enzymatic cascade system was constructed for synthesis of testolactone by specific C17 lactonization/Δ1-dehydrogenation from inexpensive androstenedione using an engineered polycyclic ketone monooxygenase (PockeMO) and an appropriate 3-ketosteroid-Δ1-dehydrogenase (ReKstD). The focused saturation mutagenesis in the substrate binding pocket was implemented for evolution of PockeMO to eliminate the bottleneck effect. A best mutant MU3 (I225L/L226V/L532Y) was obtained with 20-fold higher specific activity compared to PockeMO. The catalytic efficiency (kcat/Km) of MU3 was 171-fold higher and the substrate scope shifted to polycyclic ketones. Molecular dynamic simulations suggested that the activity was improved by stabilization of the pre-lactonization state and generation of productive orientation of 4-AD mediated by distal L532Y mutation. Based on that, the three genes, MU3, ReKstD and a ketoreductase for NADPH regeneration, were rationally integrated in one cell via expression fine-tuning to form the efficient single cell catalyst E. coli S9. The single whole-cell biocatalytic process was scaled up and could generate 9.0 g/L testolactone with the high space time yield of 1 g/L/h without steroidal by-product, indicating the potential for site-specific and one-pot synthesis of steroid.

Predictability: A new distinguishing feature of cancer?

Cancer is a consequence of stochastic (mutations, genetic, and epigenetic instabilities) and deterministic (evolutionary bottlenecks) events. Stochastic events are less amenable to prediction, whereas deterministic events yield more predictable results. The relative contribution of these opposing forces determines cancer predictability, which affects the accuracy of our prognostic predictions and is critical for treatment planning. In this study, we attempted to quantify predictability. The predictability index (PI) was defined as the median overall-survival at any time point divided by the standard error at that time. Using data obtained from the SEER program, we found striking differences in the PI of different tumors. Highly predictable tumors were malignancies of the breast, thyroid, prostate, and testis (5-year PI of 3516, 1920, 1919, and 1805, respectively). Less predictable tumors were colorectal, melanoma, and bladder (5-year PI of 1264, 1197, and 760, respectively). Least predictable were pancreatic cancer and chronic myelogenous leukemia (5-year PI of 129, and 42). PI decreased during follow-up in all examined tumors and showed sex differences in some cases. Thyroid cancer was significantly more predictable in women (5-year PI of 2579 vs. 748, p = 0.00017) and bladder cancer more predictable in men (5-year PI of 723 vs. 385, p = 0.012), Predictability is a potentially new distinguishing feature of malignancy. This study sheds light on prognostic accuracy and provides insight into the relative roles of stochastic and deterministic forces during carcinogenesis.

Small but Mighty: Genetic Diversity of the Thai Ridgeback Dog Population.

Originating in Thailand, the Thai Ridgeback dog is known for its unique fur ridge that grows in the opposite direction along its back. Selective breeding and a limited populations in Thailand have led to significant close inbreeding among related individuals. The current Thai Ridgeback population is assumed to have experienced a loss of genetic diversity and bottleneck events. Furthermore, studies on the genetic diversity and structure of Thai Ridgeback dogs are limited. Therefore, the aim of this study was to assess the genetic diversity in Thai Ridgeback dogs. Microsatellite genotyping and mitochondrial DNA D-loop sequences were used to assess genetic diversity in 105 Thai Ridgeback dogs from various farms throughout Thailand. Significant genetic diversity and minimal inbreeding were observed in the current Thai Ridgeback population. Signs of bottlenecks were not observed because the exchange of genetic material among Thai Ridgeback owners effectively preserved the genetic diversity. Moreover, the genetic parameters in this study supported owner-to-owner exchanges animals for mating programs. To sustain the genetic diversity of Thai Ridgeback dogs, the use of genetic parameters to manage genetic closeness while preserving breed characteristics is essential. These data are crucial for ensuring demographic stability, which is pivotal for long-term conservation and effective population management.