Where Are the Formerly Y-linked Genes in the Ryukyu Spiny Rat that has Lost its Y Chromosome?

It has been predicted that the highly degenerate mammalian Y chromosome will be lost eventually. Indeed, Y was lost in the Ryukyu spiny rat Tokudaia osimensis, but the fate of the formerly Y-linked genes is not completely known. We looked for all 12 ancestrally Y-linked genes in a draft T. osimensis genome sequence. Zfy1, Zfy2, Kdm5d, Eif2s3y, Usp9y, Uty, and Ddx3y are putatively functional and are now located on the X chromosome, whereas Rbmy, Uba1y, Ssty1, Ssty2, and Sry are missing or pseudogenized. Tissue expressions of the mouse orthologs of the retained genes are significantly broader/higher than those of the lost genes, suggesting that the destinies of the formerly Y-linked genes are related to their original expressions. Interestingly, patterns of gene retention/loss are significantly more similar than by chance across four rodent lineages where Y has been independently lost, indicating a level of certainty in the fate of Y-linked genes even when the chromosome is gone.

Short-term and Long-term Efficacy Evaluation of Drug-Loaded Osteoset Artificial Bone Grafting Fusion in the Treatment of Sacroiliac Joint Tuberculosis.

Objective: To analyze the short-term and long-term efficacy of Osteoset artificial bone graft fusion mixed with rifampicin for injection in the treatment of sacroiliac joint tuberculosis. Methods: A retrospective analysis was carried out on 70 patients diagnosed with sacroiliac joint tuberculosis who were admitted and underwent surgical treatment in our orthopedics department between April 2014 and May 2020. The patients were divided into three groups based on the different bone graft materials used: autogenous bone graft group (25 cases), simple lesion removal group (18 cases), and drug-loaded calcium sulfate bone graft group (27 cases). General information and surgical details of the three groups were compared. Sacroiliac X-ray and CT scans were performed at regular intervals to record pre- and post-treatment erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, bone graft fusion rates at 6, 12, and 18 months post-surgery, Majeed score for functional evaluation, and postoperative complications. Results: There was no statistically significant difference in operation time, intraoperative bleeding, and intraoperative pus removal volume among the three groups of patients (P > .05). Postoperatively, 70 patients were followed up, and the serum levels of ESR and CRP in all three groups of patients were significantly reduced at 3 months after surgery (P < .05). In the autogenous bone graft group, the bone graft fusion rates were 24.00% (6/25) at 6 months postoperatively, 76.00% (18/25) at 12 months, and 96.00% (24/25) at 18 months. In the simple lesion removal group, the bone graft fusion rates were 16.67% (3/18) at 6 months postoperatively, 27.78% (5/18) at 12 months, and 55.56% (10/18) at 18 months. In the drug-loaded calcium sulfate bone graft group, the bone graft fusion rates were 18.52% (5/27) at 6 months postoperatively, 55.56% (15/27) at 12 months, and 81.48% (22/27) at 18 months. In the autogenous bone graft group, the postoperative Majeed score averaged (91.47±4.13) points, with 13 cases rated as excellent and 10 cases rated as good, resulting in an excellent and good rate of 92.00% (23/25). The Majeed scores at 6, 12, and 18 months postoperatively were (67.19±4.22) points, (80.28±5.83) points, and (91.47±4.13) points, respectively. Among them, there were 4 excellent and 3 good cases at 6 months postoperatively, with an excellent and good rate of 28.00% (7/25). At 12 months postoperatively, there were 8 excellent and 10 good cases, with an excellent and good rate of 72.00% (18/25). At 18 months postoperatively, there were 13 excellent and 10 good cases, with an excellent and good rate of 92.00% (23/25). In the simple lesion removal group, the Majeed scores at 6, 12, and 18 months postoperatively were (59.17±3.95) points, (69.84±5.16) points, and (76.22±8.76) points, respectively. There were 2 excellent and 2 good cases at 6 months postoperatively, with an excellent and good rate of 22.22% (4/18). At 12 months postoperatively, there were 4 excellent and 3 good cases, with an excellent and good rate of 38.89% (7/18). At 18 months postoperatively, there were 5 excellent and 5 good cases, with an excellent and good rate of 55.56% (10/18). In the drug-loaded calcium sulfate bone graft group, the Majeed scores at 6, 12, and 18 months postoperatively were (63.24±4.17) points, (77.39±5.50) points, and (86.64±7.03) points, respectively. There were 3 excellent and 3 good cases at 6 months postoperatively, with an excellent and good rate of 22.22% (6/27). At 12 months postoperatively, there were 9 excellent and 7 good cases, with an excellent and good rate of 59.26% (16/27). At 18 months postoperatively, there were 10 excellent and 12 good cases, with an excellent and good rate of 81.48% (22/27). The Majeed scores for all three groups of patients showed a significant increase in the three follow-up evaluations compared to pre-treatment (P < .05). Conclusion: Drug-loaded Osteoset artificial bone graft fusion is a safe and effective method for treating bone defects after the debridement of sacroiliac joint tuberculosis lesions. It has fewer postoperative complications and achieves bone graft fusion in a shorter time compared to simple lesion removal methods.

Genetic variants underlying human bisexual behavior are reproductively advantageous.

Because human same-sex sexual behavior (SSB) is heritable and leads to fewer offspring, how SSB-associated alleles have persisted and whether they will remain in human populations are of interest. Using the UK Biobank, we address these questions separately for bisexual behavior (BSB) and exclusive SSB (eSSB) after confirming their genetic distinction. We discover that male BSB is genetically positively correlated with the number of offspring. This unexpected phenomenon is attributable to the horizontal pleiotropy of male risk-taking behavior-associated alleles because male risk-taking behavior is genetically positively correlated with both BSB and the number of offspring and because genetically controlling male risk-taking behavior abolishes the genetic correlation between male BSB and the number of offspring. By contrast, eSSB is genetically negatively correlated with the number of offspring. Our results suggest that male BSB-associated alleles are likely reproductively advantageous, which may explain their past persistence and predict their future maintenance, and that eSSB-associated alleles are likely being selected against at present.

Selective recycling of lithium from spent LiNixCoyMn1-x-yO2 cathode via constructing a synergistic leaching environment.

The global response to lithium scarcity is overstretched, and it is imperative to explore a green process to sustainably and selectively recover lithium from spent lithium-ion battery (LIB) cathodes. This work investigates the distinct leaching behaviors between lithium and transition metals in pure formic acid and the auxiliary effect of acetic acid as a solvent in the leaching reaction. A formic acid-acetic acid (FA-AA) synergistic system was constructed to selectively recycle 96.81% of lithium from spent LIB cathodes by regulating the conditions of the reaction environment to inhibit the leaching of non-target metals. Meanwhile, the transition metals generate carboxylate precipitates enriched in the leaching residue. The inhibition mechanism of manganese leaching by acetic acid and the leaching behavior of nickel or cobalt being precipitated after release was revealed by characterizations such as XPS, SEM, and FTIR. After the reaction, 90.50% of the acid can be recycled by distillation, and small amounts of the residual Li-containing concentrated solution are converted to battery-grade lithium carbonate by roasting and washing (91.62% recovery rate). This recycling process possesses four significant advantages: i) no additional chemicals are required, ii) the lithium sinking step is eliminated, iii) no waste liquid is discharged, and iv) there is the potential for profitability. Overall, this study provides a novel approach to the waste management technology of lithium batteries and sustainable recycling of lithium resources.

Ascertainment Bias in the Genomic Test of Positive Selection on Regulatory Sequences.

Evolution of gene expression mediated by cis-regulatory changes is thought to be an important contributor to organismal adaptation, but identifying adaptive cis-regulatory changes is challenging due to the difficulty in knowing the expectation under no positive selection. A new approach for detecting positive selection on transcription factor binding sites (TFBSs) was recently developed, thanks to the application of machine learning in predicting transcription factor (TF) binding affinities of DNA sequences. Given a TFBS sequence from a focal species and the corresponding inferred ancestral sequence that differs from the former at n sites, one can predict the TF-binding affinities of many n-step mutational neighbors of the ancestral sequence and obtain a null distribution of the derived binding affinity, which allows testing whether the binding affinity of the real derived sequence deviates significantly from the null distribution. Applying this test genomically to all experimentally identified binding sites of 3 TFs in humans, a recent study reported positive selection for elevated binding affinities of TFBSs. Here, we show that this genomic test suffers from an ascertainment bias because, even in the absence of positive selection for strengthened binding, the binding affinities of known human TFBSs are more likely to have increased than decreased in evolution. We demonstrate by computer simulation that this bias inflates the false positive rate of the selection test. We propose several methods to mitigate the ascertainment bias and show that almost all previously reported positive selection signals disappear when these methods are applied.

Mineralization versus polymerization pathways in heterogeneous Fenton-like reactions.

Fenton reaction has been widespread application in water purification due to the excellent oxidation performances. However, the poor cycle efficiency of Fe(III)/Fe(II) is one of the biggest bottlenecks. In this study, graphite (GP) was used as a green carbon catalyst to accelerate Fenton-like (H2O2/Fe3+ and persulfate/Fe3+) reactions by promoting ferric ion reduction and intensifying diverse peroxide activation pathways. Significantly, the carboxyl group on GP anchors iron ions to form GP-COOFe(III) which promote persulfate adsorption to form surface complexes and induce an electron transfer pathway (ETP). While the electron-rich hydroxyl and carbonyl groups will combine to from GP-COFe(II), a reductive intermediate to activate peroxide to generate free radicals (from H2O2 and PDS) or high-value iron [Fe(IV)] (from PMS). Consequently, different pathways lead to distinct degree of oxidation: i) radicals in H2O2/Fe3+/GP prefer to mineralize bisphenol A (BPA) with no selectivity; ii) Fe(IV) in PMS/Fe3+/GP partially oxidizes BPA but cannot open the aromatic ring; iii) ETP in PMS/ or PDS/Fe3+/GP drives coupling reactions to form polymeric products covered on catalyst surface. Thus, rational engineering surface functionality of graphite and selecting proper peroxides can realize on-demand selectivity and oxidation capacity in Fenton-like systems.

Evidence for the role of selection for reproductively advantageous alleles in human aging.

The antagonistic pleiotropy hypothesis posits that natural selection for pleiotropic mutations that confer earlier or more reproduction but impair the post-reproductive life causes aging. This hypothesis of the evolutionary origin of aging is supported by case studies but lacks unambiguous genomic evidence. Here, we genomically test this hypothesis using the genotypes, reproductive phenotypes, and death registry of 276,406 U.K. Biobank participants. We observe a strong, negative genetic correlation between reproductive traits and life span. Individuals with higher polygenetic scores for reproduction (PGSR) have lower survivorships to age 76 (SV76), and PGSR increased over birth cohorts from 1940 to 1969. Similar trends are seen from individual genetic variants examined. The antagonistically pleiotropic variants are often associated with cis-regulatory effects across multiple tissues or on multiple target genes. These and other findings support the antagonistic pleiotropy hypothesis of aging in humans and point to potential molecular mechanisms of the reproduction-life-span antagonistic pleiotropy.

Influence of CUREs on STEM retention depends on demographic identities.

Research has shown that undergraduate research experiences can have substantive effects on retaining students in science, technology, engineering and mathematics (STEM). However, it is impossible to provide individual research experiences for every undergraduate student, especially at large universities. Course-based undergraduate research experiences (CUREs) have become a common approach to introduce large numbers of students to research. We investigated whether a one-semester CURE that replaced a traditional introductory biology laboratory course could increase retention in STEM as well as intention to remain in STEM, if the results differed according to demography, and investigated the possible motivational factors that might mediate such an effect. Under the umbrella of the Authentic Research Connection (ARC) program, we used institutional and survey data from nine semesters and compared ARC participants to non-participants, who applied to ARC but either were not randomly selected or were selected but chose not to enroll in an ARC section. We found that ARC had significant effects on demographic groups historically less likely to be retained in STEM: ARC participation resulted in narrowing the gaps in graduation rates in STEM (first vs continuing-generation college students) and in intention to major in STEM [females vs males, Persons Excluded because of Ethnicity or Race (PEERs) vs non-PEERs]. These disproportionate boosts in intending STEM majors among ARC students coincide with their reporting a greater sense of student cohesiveness, retaining more interest in biology, and commenting more frequently that the course provided a useful/valuable learning experience. Our results indicate that CUREs can be a valuable tool for eliminating inequities in STEM participation, and we make several recommendations for further research.

COL, a pipeline for identifying putatively functional back-splicing.

Circular RNAs (circRNAs) are a class of generally non-coding RNAs produced by back-splicing. Although the vast majority of circRNAs are likely to be products of splicing error and thereby confer no benefits to organisms, a small number of circRNAs have been found to be functional. Identifying other functional circRNAs from the sea of mostly non-functional circRNAs is an important but difficult task. Because available experimental methods for this purpose are of low throughput or versality and existing computational methods have limited reliability or applicability, new methods are needed. We hypothesize that functional back-splicing events that generate functional circRNAs (i) exhibit substantially higher back-splicing rates than expected from the total splicing amounts, (ii) have conserved splicing motifs, and (iii) show unusually high back-splicing levels. We confirm these features in back-splicing shared among human, macaque, and mouse, which should enrich functional back-splicing. Integrating the three features, we design a computational pipeline named COL for identifying putatively functional back-splicing. Using experimentally verified functional back-splicing as a benchmark, we find COL to outperform a commonly used computational method with a similar data requirement. We conclude that COL is an efficient and versatile method for rapid identification of putatively functional back-splicing and circRNAs that can be experimentally validated.

Effective fitness under fluctuating selection with genetic drift.

The natural environment fluctuates for virtually every population of organisms. As a result, the fitness of a mutant may vary temporally. While commonly used for summarizing the effect of fluctuating selection on the mutant, geometric mean fitness can be misleading under some circumstances due to the influence of genetic drift. Here, we show by mathematical proof and computer simulation that, with genetic drift, the geometric mean fitness does not accurately reflect the overall effect of fluctuating selection. We propose an alternative measure based on the average expected allele frequency change caused by selection and demonstrate that this measure-effective fitness-better captures the overall effect of fluctuating selection in the presence of drift.

Genomic estimates of mutation and substitution rates contradict the evolutionary speed hypothesis of the latitudinal diversity gradient.

The latitudinal diversity gradient (LDG) refers to a decrease in biodiversity from the equator to the poles. The evolutionary speed hypothesis, backed by the metabolic theory of ecology, asserts that nucleotide mutation and substitution rates per site per year are higher and thereby speciation rates are higher at higher temperatures, generating the LDG. However, prior empirical investigations of the relationship between the temperature and mutation or substitution rate were based on a few genes and the results were mixed. We here revisit this relationship using genomic data. No significant correlation between the temperature and mutation rate is found in 13 prokaryotes or in 107 eukaryotes. An analysis of 234 diverse trios of bacterial taxa indicates that the synonymous substitution rate is not significantly associated with the growth temperature. The same data, however, reveal a significant negative association between the nonsynonymous substitution rate and temperature, which is explainable by a larger fraction of detrimental nonsynonymous mutations at higher temperatures due to a stronger demand for protein stability. We conclude that the evolutionary speed hypothesis of the LDG is unsupported by genomic data and advise that future mechanistic studies of the LDG should focus on other hypotheses.

Ascertainment bias in the genomic test of positive selection on regulatory sequences.

Evolution of gene expression mediated by cis-regulatory changes is thought to be an important contributor to organismal adaptation, but identifying adaptive cis-regulatory changes is challenging due to the difficulty in knowing the expectation under no positive selection. A new approach for detecting positive selection on transcription factor binding sites (TFBSs) was recently developed, thanks to the application of machine learning in predicting transcription factor (TF) binding affinities of DNA sequences. Given a TFBS sequence from a focal species and the corresponding inferred ancestral sequence that differs from the former at n sites, one can predict the TF binding affinities of many n-step mutational neighbors of the ancestral sequence and obtain a null distribution of the derived binding affinity, which allows testing whether the binding affinity of the real derived sequence deviates significantly from the null distribution. Applying this test genomically to all experimentally identified binding sites of three TFs in humans, a recent study reported positive selection for elevated binding affinities of TFBSs. Here we show that this genomic test suffers from an ascertainment bias because, even in the absence of positive selection for strengthened binding, the binding affinities of known human TFBSs are more likely to have increased than decreased in evolution. We demonstrate by computer simulation that this bias inflates the false positive rate of the selection test. We propose several methods to mitigate the ascertainment bias and show that almost all previously reported positive selection signals disappear when these methods are applied.

Transcriptomic analysis reveals the rareness of genetic assimilation of gene expression in environmental adaptations.

Genetic assimilation is the evolutionary process by which an environmentally induced phenotype becomes genetically encoded and constitutive. Genetic assimilation has been proposed as a concluding step in environmental adaptation, but its prevalence has not been systematically investigated. Analyzing transcriptomic data collected upon reciprocal transplant, we address this question in the experimental evolution, domestication, or natural evolution of seven diverse species. We find that genetic assimilation of environment-induced gene expression is the exception rather than the rule and that substantially more genes retain than lose their expression plasticity upon organismal adaptations to new environments. The probability of genetic assimilation of gene expression decreases with the expression level and number of transcription factors controlling the gene, suggesting that genetic assimilation results primarily from passive losses of gene regulations that are not mutationally robust. Hence, for gene expression, our findings argue against the purported generality or importance of genetic assimilation to environmental adaptation.

Detecting natural selection in trait-trait coevolution.

No phenotypic trait evolves independently of all other traits, but the cause of trait-trait coevolution is poorly understood. While the coevolution could arise simply from pleiotropic mutations that simultaneously affect the traits concerned, it could also result from multivariate natural selection favoring certain trait relationships. To gain a general mechanistic understanding of trait-trait coevolution, we examine the evolution of 220 cell morphology traits across 16 natural strains of the yeast Saccharomyces cerevisiae and the evolution of 24 wing morphology traits across 110 fly species of the family Drosophilidae, along with the variations of these traits among gene deletion or mutation accumulation lines (a.k.a. mutants). For numerous trait pairs, the phenotypic correlation among evolutionary lineages differs significantly from that among mutants. Specifically, we find hundreds of cases where the evolutionary correlation between traits is strengthened or reversed relative to the mutational correlation, which, according to our population genetic simulation, is likely caused by multivariate selection. Furthermore, we detect selection for enhanced modularity of the yeast traits analyzed. Together, these results demonstrate that trait-trait coevolution is shaped by natural selection and suggest that the pleiotropic structure of mutation is not optimal. Because the morphological traits analyzed here are chosen largely because of their measurability and thereby are not expected to be biased with regard to natural selection, our conclusion is likely general.

On the Decoupling of Evolutionary Changes in mRNA and Protein Levels.

Variation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the correlation between mRNA and protein levels. Here, we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of the model over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level; this observation held true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and the translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene expression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic data.

Contraception ends the genetic maintenance of human same-sex sexual behavior.

Because human same-sex sexual behavior (SSB) is heritable and leads to fewer offspring, it is puzzling why SSB-associated alleles have not been selectively purged. Current evidence supports the antagonistic pleiotropy hypothesis that SSB-associated alleles benefit individuals exclusively performing opposite-sex sexual behavior by increasing their number of sexual partners and consequently their number of offspring. However, by analyzing the UK Biobank, here, we show that having more sexual partners no longer predicts more offspring since the availability of oral contraceptives in the 1960s and that SSB is now genetically negatively correlated with the number of offspring, suggesting a loss of SSB's genetic maintenance in modern societies.

Chance promoter activities illuminate the origins of eukaryotic intergenic transcriptions.

It is debated whether the pervasive intergenic transcription from eukaryotic genomes has functional significance or simply reflects the promiscuity of RNA polymerases. We approach this question by comparing chance promoter activities with the expression levels of intergenic regions in the model eukaryote Saccharomyces cerevisiae. We build a library of over 105 strains, each carrying a 120-nucleotide, chromosomally integrated, completely random sequence driving the potential transcription of a barcode. Quantifying the RNA concentration of each barcode in two environments reveals that 41-63% of random sequences have significant, albeit usually low, promoter activities. Therefore, even in eukaryotes, where the presence of chromatin is thought to repress transcription, chance transcription is prevalent. We find that only 1-5% of yeast intergenic transcriptions are unattributable to chance promoter activities or neighboring gene expressions, and these transcriptions exhibit higher-than-expected environment-specificity. These findings suggest that only a minute fraction of intergenic transcription is functional in yeast.

Decoupling of evolutionary changes in mRNA and protein levels.

Variation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the correlation between mRNA and protein levels. Here we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of the model over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level, which is true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and its translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene expression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic studies.