Increased Floral Rewards due to Local Adaptation Drives Plant Ecological Speciation via Learned Preferences of Pollinators.

AbstractIn animal-pollinated plants, the growth environment and pollination environment are two important agents of natural selection. However, their simultaneous effects on plant speciation remain underexplored. Here, we report a theoretical finding that if plants' local adaptation to the growth environment increases their floral rewards for pollinators, it can strongly facilitate ecological speciation in plants. We consider two evolving plant traits, vegetative and floral signal traits, in a population genetic model for two plant populations under divergent selection from different growth environments. The vegetative trait determines plants' local adaptation. Locally adapted plants reward pollinators better than maladapted plants. By associative learning, pollinators acquire learned preferences for floral signal traits expressed by better-rewarding plants. If pollinators' learned preferences become divergent between populations, floral signal divergence occurs and plants develop genetic associations between vegetative and floral signal traits, leading to ecological speciation via a two-allele mechanism. Interestingly, speciation is contingent on whether novel floral signal variants arise before or after plant populations become locally adapted to the growth environment. Our results suggest that simultaneous selection from growth and pollination environments might be important for the ecological speciation of animal-pollinated plants.

Combinational Elastography.

Heart failure (HF) can cause liver congestion and stiffness. Elastography is used to noninvasively measure organ stiffness. Liver fibrosis (LF) is monitored by shear wave and strain elastography. However, shear wave velocity (Vs) on shear wave elastography varies under the influence of fibrosis and congestion, and the LF index by strain elastography reflects only LF progression. Little is known about the usefulness of these methods in HF patients. This prospective study evaluated combined shear wave and strain elastography (i.e., combinational elastography) for assessing liver congestion. A total of 51 patients with HF (33 outpatients and 18 inpatients) and 10 healthy participants were included. Further, the relationships between combinational elastography and clinical characteristics in 51 patients with HF and the effects of medical treatment on these relationships in 18 inpatients with HF were investigated. Vs was significantly higher in the HF group than in the control group (1.68 ± 0.47 versus 1.21 ± 0.16, P = 0.002). The LF index did not significantly differ (1.39 ± 0.40 versus 1.33 ± 0.15, P = 0.680). Vs decreased after treatment (from 2.01 ± 0.61 to 1.62 ± 0.49 m/seconds; P = 0.026), while the LF index did not change (from 1.21 ± 0.29 to 1.26 ± 0.27; P = 0.664). Brain natriuretic peptide level (r = 0.343; P = 0.003) and composite congestion scores (r = 0.455; P < 0.001) were correlated with Vs. Combinational elastography is useful for assessing liver congestion, differentiating between liver congestion and fibrosis, and assessing therapeutic effects in HF patients.

Criteria for placenta accreta spectrum in the International Federation of Gynaecology and Obstetrics classification, and topographic invasion area are associated with massive hemorrhage in patients with placenta previa.

INTRODUCTION: Placenta previa with placenta accreta spectrum (PAS) is a life-threatening disease that results in massive hemorrhage. The clinical and histologic criteria of PAS were adopted according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. We aimed to investigate whether FIGO criteria and topography were associated with maternal complications in patients with placenta previa. MATERIAL AND METHODS: Patients with placenta previa who underwent cesarean section at our institution between January 2003 and December 2019 were identified. First, they were divided based on FIGO classification, as follows: Group A, with clinical criteria; Group B, with histologic criteria; and Group C: without clinical or histologic criteria. Next, cases with PAS were classified according to the topographic invasion area, as follows: type 1, upper posterior bladder; type 2, lower posterior bladder; type 3, parametrium; type 4, posterior lower uterine segment. Predictive factors for massive hemorrhage were retrospectively analyzed. RESULTS: Among the 350 patients, 24 (6.9%) were classified as Group A, 16 (4.6%) as Group B and 310 (88.5%) as Group C. Regarding maternal history and hemostatic procedures, there were no significant factors other than hysterectomy (p < .01) in Groups A and B. The volume of blood loss in both Groups A and B was greater than in Group C (p < .01). The rates of uterine artery embolization and blood transfusion were higher in Groups A and B than in Group C (p < .01). In addition, there were no significant factors other than hysterectomy between Groups A and B. In the multivariate analysis for massive hemorrhage, Group A (odds ratio: 2.73, p = .04) and Group B (odds ratio: 12.69, p < .01) were identified as independent predictive factors. In addition, massive hemorrhage was closely related to the lower posterior bladder and parametrial invasion in both Groups A and B. CONCLUSIONS: Both clinical and histologic criteria for PAS in the FIGO classification were associated with massive hemorrhage. Diagnosing clinical PAS using the FIGO classification, additional hemostatic procedures might be necessary according to the topographic invasion area.

Multi-dimensional diffusion process of allele frequencies in population genetics.

One of the ultimate goals of population genetics is to theoretically describe the behavior of allele frequency. Diffusion theory has been commonly used for this purpose mainly in one-locus one-population models, although it is not easy to handle diffusion theory in models with multiple loci or with multiple populations. This review introduces several successful cases, where multi-dimensional diffusion equations contributed to addressing evolutionary questions, thereby demonstrating its strong potential in population genetics.

The use of magnetic resonance imaging to predict placenta previa with placenta accreta spectrum.

INTRODUCTION: Massive hemorrhage due to placenta previa with placenta accreta spectrum is associated with high maternal mortality and morbidity. Therefore, accurate prediction of placenta previa with placenta accreta spectrum is essential; magnetic resonance imaging (MRI) is a useful tool for this purpose. This study investigated novel predictors of anterior and posterior placenta previa with placenta accreta spectrum using MRI. MATERIAL AND METHODS: This was a retrospective study at a tertiary obstetrics hospital in Japan. The singleton patients with placenta previa who were scanned with MRI prenatally and had a cesarean section at our institution between 2007 and 2018 were included. The prediction of anterior and posterior placenta previa with placenta accreta spectrum was evaluated using four MRI findings: heterogeneous signals in the placenta, dark T2-weighted intraplacental bands, myometrial thinning or interruption, and focal uterine bulging. The prediction of posterior placenta previa with placenta accreta spectrum was performed using the quantification of cervical varicosities, which were defined as the ratio of the distance between the minimum distance from the most dorsal cervical varicosities (a) to the deciduous and amniotic placenta (b) on a sagittal image. RESULTS: Among 202 patients, 14 (6.9%) patients were pathologically diagnosed as having placenta accreta spectrum. Further, 38 (18.8%) patients had anterior placenta previa and 164 (81.2%) patients had posterior placenta previa. When anterior placenta previa with placenta accreta spectrum was predicted using at least one of the four MRI findings, the sensitivity and specificity of the anterior placenta previa with placenta accreta spectrum were 87.5% and 86.7%, respectively. In contrast, the sensitivity and specificity of posterior placenta previa with placenta accreta spectrum were 42.9% and 96.2%, respectively. But when the A/B ratio was set at 0.20, the sensitivity and specificity of the prediction for posterior placenta previa with placenta accreta spectrum using cervical varicosities were 100.0% and 89.2%, respectively. CONCLUSIONS: The findings of MRI to predict the anterior placenta previa with placenta accreta spectrum were different from posterior placenta previa. The cervical varicosities may be useful in predicting posterior placenta previa with placenta accreta spectrum.

Placenta previa may acquire invasive nature by factors associated with epithelial-mesenchymal transition and matrix metalloproteinases.

AIM: To investigate the differences in epithelial-mesenchymal transition (EMT)- and matrix metalloproteinases (MMP)-related factors among placenta previa with and without placenta accreta spectrum (PAS) (n = 69), and normal placenta (n = 51). METHODS: The women diagnosed with placenta previa with or without PAS, and normal placentas, who delivered at our institution between 2006 and 2016, were enrolled. The difference of EMT-related factors' expression by immunochemical analysis in chorionic villi and decidual cells between the normal placenta and placenta previa with or without PAS were evaluated. RESULTS: In chorionic villi of placenta previa with and without PAS, E-cadherin expression decreased, while that of ZEB1, SNAIL2 and MMP-9 increased than that in normal placenta. In decidual cells of placenta previa with and without PAS, expression of vimentin, ZEB1 and MMP-9 increased than that in normal placenta. In placenta previa with and without PAS, there was strong co-expression of ZEB1 and vimentin in chorionic villi, of ZEB1 and MMP-2 or MMP-9 in decidual cells, and of SNAIL2 and vimentin or MMP-9 in both chorionic villi and decidual cell. Vimentin expression in both chorionic villi and decidual cells was higher in placenta previa with PAS (n = 18) than in placenta previa without PAS (n = 51). MMP-2 expression in decidual cells was higher in placenta previa with PAS than in placenta previa without PAS. CONCLUSION: This study revealed that EMT- and MMP-associated factors may be related to placenta previa with and without PAS. Furthermore, placenta previa without PAS may acquire invasive nature.

Pretreatment Neutrophil-to-Lymphocyte Ratio Was a Predictor of Lymph Node Metastasis in Endometrial Cancer Patients.

OBJECTIVE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported to be useful as markers for prognostic factors and metastasis in several cancers. The aim of this study was to identify the predictor of lymph node (LN) metastasis by pretreatment NLR and PLR in patients with endometrial cancer. METHODS: Medical charts of the patients with endometrial cancers that received primary surgery at our hospital between 2007 and 2013 were retrospectively analyzed. The cutoff value was calculated from the receiver operating characteristics (ROC) curve. Clinicopathological parameters including inflammatory markers were evaluated for LN metastasis using multiple logistic regression analysis. RESULTS: Among 197 patients enrolled in the study, LN metastasis was observed in 25 patients (13%). ROC curves demonstrated that the best cutoff value of NLR for predicting LN metastasis was 2.18 and that of PLR was 206. In univariate analysis, several pathological factors, NLR, and PLR were identified as predictors of LN metastasis. In multiple logistic regression analysis, lymphovascular invasion and NLR were found to be significantly correlated with LN metastasis (p = 0.002, 0.039). CONCLUSION: A higher pretreatment NLR was identified as a predictor of LN metastasis in endometrial cancers. Although further study is needed to confirm the results, NLR could be a candidate clinical marker for detection of LN metastasis.

Thrombotic events induce the worse prognosis in ovarian carcinomas and frequently develop in ovarian clear cell carcinoma.

BACKGROUND: This study aimed to examine the clinical significance and risk factors of thromboembolic events (TEEs) in patients with ovarian carcinoma. METHODS: Patients with ovarian carcinoma treated at our hospital between 2000 and 2017 were identified. The risk factors of TEEs, including venous TEEs and arterial TEEs, and the association between TEEs and prognosis were investigated. Patients with TEEs were classified into two groups: those with severe TEEs, defined as patients who required urgent treatment for deep vein thrombosis, massive pulmonary embolism, acute myocardial infarction, and symptomatic cerebral infarction, and those with mild TEEs. The risk factors of severe TEEs and the association between severe TEEs and prognosis were investigated. RESULTS: A total of 369 patients were enrolled. Among them, 53 patients (14.4%) were complicated with TEEs. Clear cell carcinoma (CCC) was a greater risk factor of TEEs than serous carcinoma (hazard ratio [HR] = 2.81, p = 0.03). In multivariate analysis for survival, TEEs were a prognostic factor of poor progression-free survival (PFS; HR = 2.90, p < 0.01) and overall survival (OS; HR = 2.89, p < 0.01). Among 53 patients with TEEs, 17 (32.1%) developed severe TEEs. CCC was strongly associated with severe TEEs (HR = 42.6, p = 0.02). Multivariate analysis for survival demonstrated that severe TEEs were a risk factor of worse PFS (HR = 4.34, p < 0.01) and OS (HR = 3.30, p = 0.03). CONCLUSION: TEEs induced poor prognosis and was associated with CCC. A standard treatment for CCC should be included in the strategy of TEEs.

[Acquisition of Pulmonary Vein and Left Atrium with Trigger Angiography Non-contrast Enhanced MRI in Diastolic Phase].

OBJECTIVE: The aim of this study was to compare the image quality and the visibility of trigger angiography non-contrast enhanced (TRANCE) in diastolic phase and 3D balanced steady-state free precession (3D SSFP) sequences for the evaluation of pulmonary vein (PV) and left atrium (LA). METHODS: About 10 volunteers underwent TRANCE and 3D SSFP imaging on 1.5 T MRI. Axial images were reconstructed and regions of interest were positioned on the right superior pulmonary vein (RSPV), right inferior pulmonary vein (RIPV), left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV), LA, and left atrial appendage (LAA). Contrast-to-noise ratio (CNR) between each part and muscle were calculated and compared between two sequences. The two observers independently scored the image quality of each image on the basis of PV, LA, and LAA anatomy and contour using a five-point scale, which scores were averaged and compared. RESULTS: CNRs on RSPV, RIPV, LSPV, LIPV, LA, and LAA were significantly higher in TRANCE sequence compared with 3D SSFP sequence. On visual assessment, TRANCE showed significantly higher scores in RSPV, RIPV, LSPV, LIPV compared with 3D SSFP sequence. CONCLUSIONS: TRANCE provides higher image quality in PVs and LA compared with 3D SSFP on 1.5 T MRI. On visual assessment, TRANCE provides better visibility of PVs anatomy and contour compared with 3D SSFP.

[FeFe]-Hydrogenase H-Cluster Mimics with Unique Planar µ-(SCH2 )2 ER2 Linkers (E=Ge and Sn).

Analogues of the [2Fe-2S] subcluster of hydrogenase enzymes in which the central group of the three-atom chain linker between the sulfur atoms is replaced by GeR2 and SnR2 groups are studied. The six-membered FeSCECS rings in these complexes (E=Ge or Sn) adopt an unusual conformation with nearly co-planar SCECS atoms perpendicular to the Fe-Fe core. Computational modelling traces this result to the steric interaction of the Me groups with the axial carbonyls of the Fe2 (CO)6 cluster and low torsional strain for GeMe2 and SnMe2 moieties owing to the long C-Ge and C-Sn bonds. Gas-phase photoelectron spectroscopy of these complexes shows a shift of ionization potentials to lower energies with substantial sulfur orbital character and, as supported by the computations, an increase in sulfur character in the predominantly metal-metal bonding HOMO. Cyclic voltammetry reveals that the complexes follow an ECE-type reduction mechanism (E=electron transfer and C=chemical process) in the absence of acid and catalysis of proton reduction in the presence of acid. Two cyclic tetranuclear complexes featuring the sulfur atoms of two Fe2 S2 (CO)6 cores bridged by CH2 SnR2 CH2 , R=Me, Ph, linkers were also obtained and characterized.

Evaluating the potential roles of the Gray and Extension loci in the coat coloration of Thoroughbred racing horses.

Horses have substantial variation in coat color, and the genetic loci responsible for the coat color variations have been well investigated. It has been believed that some color variations should follow a single-locus Mendelian law. Examples include the Gray locus that causes the gray phenotype and the Extension locus that specifies the chestnut phenotype. We reevaluated the roles of the Gray and Extension loci by using a large number of mating records of Thoroughbred racing horses. We showed that the data indeed fits the Mendelian law extremely well for the two loci. Furthermore, we demonstrated that the Extension and Agouti loci might have an additional role in determining the degree of melanin that should distinguish bay, dark bay, and brown.

A strongly CD34-positive meningioma that was difficult to distinguish from a solitary fibrous tumor.

Fibrous or transitional meningioma and solitary fibrous tumor (SFT) are frequently difficult to differentiate from each other on the basis of histopathology. It is extremely unusual for a meningioma to exhibit diffuse, strongly positive immunoreactivity for cluster of differentiation 34 (CD34), and this has never been previously reported from a histopathological specimen. A patient with transitional meningioma that exhibited strongly positive for CD34, which has been regarded as characteristic of SFT and is considered to be useful for distinguishing the latter from meningioma, is reported.

Combinational elastography prior to pericardiectomy to assess liver condition in patients with constrictive pericarditis.

A 68-year-old man was diagnosed with pericarditis associated with immunoglobulin G4-related disease and was administered prednisolone 2 years prior to presentation. During the process of tapering off from prednisolone 1 year later, edema of the lower legs and pleural effusion worsened. He gradually developed dyspnea on exertion, and laboratory examinations revealed elevated liver enzyme levels. Diuretics were administered; however, the symptoms did not resolve. Transthoracic echocardiography and cardiac catheterization revealed findings consistent with those of constrictive pericarditis. Pericardiectomy was considered and the perioperative risks due to possible recovery from liver dysfunction were discussed. Combinational elastography was subsequently performed. The results indicated the absence of liver fibrosis, suggesting that liver dysfunction was attributable to liver congestion; thus, the liver dysfunction was considered reversible. Subsequently, pericardiectomy was performed. Given that constrictive pericarditis can lead to liver dysfunction due to congestion, the perioperative risk is often controversial when considering surgical interventions. Learning objective: Combinational elastography may be useful in the preoperative evaluation of patients with cardiac diseases complicated by liver dysfunction to distinguish liver fibrosis, understand the pathogenesis of liver dysfunction, and determine subsequent treatment strategies.

Evaluation of thyroid congestion in patients with heart failure using shear wave elastography: An observational study.

Shear wave elastography (SWE) is a noninvasive method for measuring organ stiffness. Liver stiffness measured using SWE reflects hepatic congestion in patients with heart failure (HF). However, little is known about the use of SWE to assess other organ congestions. This study aimed to evaluate the utility of SWE for assessing not only the liver but also thyroid congestion in patients with HF. This prospective study included 21 patients with HF who have normal thyroid lobes (age: 77.0 ±â€…11.0, men: 14). Thyroid and liver stiffness were measured by SWE using the ARIETTA 850 ultrasonography system (Fujifilm Ltd., Tokyo, Japan). SWE of the thyroid was performed on B-mode ultrasonography; a target region was identified within a region of interest. SWE was performed in each lobe of the thyroid gland. Five measurements were taken at the same location and the averages were recorded for comparison. We investigated the relationship between SWE for evaluating thyroid stiffness and the clinical characteristics of patients with HF. SWE of the thyroid was significantly correlated with SWE of the liver (R = 0.768, P < .001), thyroid stimulation hormone (R = 0.570, P = .011), free thyroxine (R = 0.493, P = .032), estimated right atrial pressure (RAP; R = 0.468, P = .033), and composite congestion score (R = 0.441, P = .045). SWE may be useful for evaluating thyroid stiffness and assessing the degree of thyroid congestion. Thyroid congestion may reflect the elevation of RAP and cause thyroid dysfunction through organ congestion.

Accuracy of Shunt Volume Measured by Three-Dimensional Echocardiography and Cardiac Magnetic Resonance in Patients With an Atrial Septal Defect and a Dilated Right Ventricle.

BACKGROUND: The accuracy of right ventricular (RV) quantification by three-dimensional echocardiography (3DE) has been reported mainly in patients with a normal right ventricle (RV). However, there are no data regarding the accuracy of 3DE in patients with a dilated RV, as in shunt diseases. In this study, we evaluated the accuracy of 3DE and that of volumetric (Vol) cardiac magnetic resonance (CMR) for assessment of RV and left ventricular (LV) stroke volume (SV) and the pulmonary (Qp)/systemic (Qs) blood flow ratio in patients with an atrial septal defect (ASD) using the two-dimensional phase contrast (2DPC) method as the gold standard. METHODS: We retrospectively investigated 83 patients with ASD who underwent transcatheter closure and clinically indicated CMR and 3DE examinations. The ratio Qp/Qs was calculated using RV and LV SV measured by full-volume volumetric 3DE (Vol-3DE) and CMR (Vol-CMR) and by two-dimensional pulsed Doppler quantification (2D-Dop); the parameters were compared using 2DPC-CMR as the gold standard. RESULTS: There was no significant difference in the Qp/Qs value between 2DPC-CMR and Vol-3DE (2.29 ± 0.70 vs 2.21 ± 0.63, P = .79) and 2D-Dop (vs 2.21 ± 0.65, P = 1.00); however, a significant difference was found between 2DPC-CMR and Vol-CMR (P < .001). The Qp/Qs value obtained using Vol-3DE showed the best correlation with 2DPC-CMR (r = 0.93, P < .001). The RV and LV SV values obtained by Vol-3DE showed the best correlation with 2DPC-CMR (RV SV, r = 0.82, P < .001; LV SV, r = 0.73, P < .001), although the absolute values were underestimated. CONCLUSION: Qp/Qs was more accurately evaluated by Vol-3DE than by Vol-CMR or 2D-Dop. Three-dimensional echocardiography assessment was feasible and reproducible even in a dilated RV.

Factors Influencing Acceptance of the Chairperson Position at Annual Scientific Meetings of the Japanese Circulation Society　- A Questionnaire Survey in Chugoku District.

Background: The Japanese Circulation Society survey revealed that Japanese female cardiologists exhibited a trend to refuse the chairperson position; however, the causal factors remain uncertain. Methods and Results: We distributed a questionnaire survey among chairpersons of the Chugoku regional meeting in November 2022. The rate of chair acceptance at the annual meeting tended to increase as the chairperson's experience grew (first time chairing a meeting, 25.0%; 2-3 times, 33.3%; 4-5 times, 53.8%; ≥6 times, 70.0%; P=0.021). Conclusions: Providing inexperienced members with the chance to perform the role of chairperson will lead to them accepting to chair annual meetings.

Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.

Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m2). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; P<0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.

Assessment of organ congestion in patients with heart failure by ultrasonography.

In recent years, there has been a growing interest in assessing congestion of organs (e.g., liver, kidneys, lungs, intestines) in patients with heart failure (HF). HF involves an increased risk of mortality, thereby making it important to evaluate organ congestion. Ultrasonography is a useful tool for noninvasive and repeatable evaluation of patients with HF. Noninvasive evaluation of organ congestion can also be used to assess hemodynamics. It may further be useful for elucidating organ cross-talk in patients with HF. This review discusses the clinical implications of evaluating organ congestion by ultrasonography.

Muller's ratchet of the Y chromosome with gene conversion.

Muller's ratchet is a process in which deleterious mutations are fixed irreversibly in the absence of recombination. The degeneration of the Y chromosome, and the gradual loss of its genes, can be explained by Muller's ratchet. However, most theories consider single-copy genes, and may not be applicable to Y chromosomes, which have a number of duplicated genes in many species, which are probably undergoing concerted evolution by gene conversion. We developed a model of Muller's ratchet to explore the evolution of the Y chromosome. The model assumes a nonrecombining chromosome with both single-copy and duplicated genes. We used analytical and simulation approaches to obtain the rate of gene loss in this model, with special attention to the role of gene conversion. Homogenization by gene conversion makes both duplicated copies either mutated or intact. The former promotes the ratchet, and the latter retards, and we ask which of these counteracting forces dominates under which conditions. We found that the effect of gene conversion is complex, and depends upon the fitness effect of gene duplication. When duplication has no effect on fitness, gene conversion accelerates the ratchet of both single-copy and duplicated genes. If duplication has an additive fitness effect, the ratchet of single-copy genes is accelerated by gene duplication, regardless of the gene conversion rate, whereas gene conversion slows the degeneration of duplicated genes. Our results suggest that the evolution of the Y chromosome involves several parameters, including the fitness effect of gene duplication by increasing dosage and gene conversion rate.

Functional Innovation through Gene Duplication Followed by Frameshift Mutation.

In his influential book "Evolution by Gene Duplication", Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. To this end, we here report an exhaustive survey of the genomes of human, mouse, zebrafish, and fruit fly. We identified 80 duplicate genes that involved frameshift mutations after duplication. The frameshift mutation preferentially located close to the C-terminus in most cases (55/88), which indicated that a frameshift mutation that changed the reading frame in a small part at the end of a duplicate may likely have contributed to adaptive evolution (e.g., human genes NOTCH2NL and ARHGAP11B) otherwise too deleterious to survive. A few cases (11/80) involved multiple frameshift mutations, exhibiting various patterns of modifications of the reading frame. Functionality of duplicate genes involving frameshift mutations was confirmed by sequence characteristics and expression profile, suggesting a potential role of frameshift mutation in creating functional novelty. We thus showed that genomes have non-negligible numbers of genes that have experienced frameshift mutations following gene duplication. Our results demonstrated the potential importance of frameshift mutations in molecular evolution, as Ohno verbally argued 50 years ago.