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.

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.

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.

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.

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, 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 negatively genetically correlated with the number of offspring, indicating a loss of SSB’s genetic maintenance in modern societies.

Synonymous mutations in representative yeast genes are mostly strongly non-neutral.

Synonymous mutations in protein-coding genes do not alter protein sequences and are thus generally presumed to be neutral or nearly neutral1-5. Here, to experimentally verify this presumption, we constructed 8,341 yeast mutants each carrying a synonymous, nonsynonymous or nonsense mutation in one of 21 endogenous genes with diverse functions and expression levels and measured their fitness relative to the wild type in a rich medium. Three-quarters of synonymous mutations resulted in a significant reduction in fitness, and the distribution of fitness effects was overall similar-albeit nonidentical-between synonymous and nonsynonymous mutations. Both synonymous and nonsynonymous mutations frequently disturbed the level of mRNA expression of the mutated gene, and the extent of the disturbance partially predicted the fitness effect. Investigations in additional environments revealed greater across-environment fitness variations for nonsynonymous mutants than for synonymous mutants despite their similar fitness distributions in each environment, suggesting that a smaller proportion of nonsynonymous mutants than synonymous mutants are always non-deleterious in a changing environment to permit fixation, potentially explaining the common observation of substantially lower nonsynonymous than synonymous substitution rates. The strong non-neutrality of most synonymous mutations, if it holds true for other genes and in other organisms, would require re-examination of numerous biological conclusions about mutation, selection, effective population size, divergence time and disease mechanisms that rely on the assumption that synoymous mutations are neutral.

The Effects of Chinese Herbal Decoction Combined with Recombinant Human Interferon α2b on MRI Imaging, Tumor Markers, and Immune Function in Patients with Renal Cell Carcinoma.

BACKGROUND: To explore the clinical efficacy of traditional Chinese medicine decoction combined with recombinant human interferon α2b in the treatment of renal cell carcinoma (RCC). METHODS: 68 RCC patients were divided into the control group and treatment group (n = 34). The control group was treated with recombinant human interferon α2b, and the treatment group was treated with traditional Chinese medicine decoction on the basis of the control group. The clinical efficacy and life quality were observed. At the same time, the changes of immune function before and after treatment were compared. RESULTS: After one course of treatment, the effective rate and clinical benefit rate of the treatment group were higher than those of the control group. The Karnofsky score in the treatment group was better than that in the control group. In improving the immune function, the treatment group was better than the control group in increasing CD3+ and CD4+ and reducing CD8+. CONCLUSION: Traditional Chinese medicine decoction combined with recombinant human interferon α2b has a good effect on the treatment of RCC. It can not only improve the common clinical symptoms of patients but also improve the quality of life and cellular immune function of patients.

Unbiased inference of the fitness landscape ruggedness from imprecise fitness estimates.

Fitness landscapes map genotypes to their corresponding fitness under given environments and allow explaining and predicting evolutionary trajectories. Of particular interest is the landscape ruggedness or the unevenness of the landscape, because it impacts many aspects of evolution such as the likelihood that a population is trapped in a local fitness peak. Although the ruggedness has been inferred from a number of empirically mapped fitness landscapes, it is unclear to what extent this inference is affected by fitness estimation error, which is inevitable in the experimental determination of fitness landscapes. Here, we address this question by simulating fitness landscapes under various theoretical models, with or without fitness estimation error. We find that all eight examined measures of landscape ruggedness are overestimated due to imprecise fitness quantification, but different measures are affected to different degrees. We devise a method to use replicate fitness measures to correct this bias and show that our method performs well under realistic conditions. We conclude that previously reported fitness landscape ruggedness is likely upward biased owing to the negligence of fitness estimation error and advise that future fitness landscape mapping should include at least three biological replicates to permit an unbiased inference of the ruggedness.

Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.

PDCD10, also known as CCM3, is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in C. elegans and Drosophila have shown a pivotal role of the PDCD10-GCKIII complex in maintaining epithelial integrity. Here, we found that mice deficient of Pdcd10 or Stk24/25 in the kidney tubules developed polyuria and displayed increased water consumption. Although the expression levels of aquaporin genes were not decreased, the levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells were decreased in Pdcd10- and Stk24/25-deficient mice. This loss of Aqp2 was associated with increased expression and membrane targeting of Ezrin and phosphorylated Ezrin, Radixin, Moesin (p-ERM) proteins and impaired intracellular vesicle trafficking. Treatment with Erlotinib, a tyrosine kinase inhibitor promoting exocytosis and inhibiting endocytosis, normalized the expression level and membrane abundance of Aqp2 protein, and partially rescued the water reabsorption defect observed in the Pdcd10-deficient mice. Our current study identified the PDCD10-STK-ERM signaling pathway as a potentially novel pathway required for water balance control by regulating vesicle trafficking and protein abundance of AQP2 in the kidneys.

The evolution of red color vision is linked to coordinated rhodopsin tuning in lycaenid butterflies.

Color vision has evolved multiple times in both vertebrates and invertebrates and is largely determined by the number and variation in spectral sensitivities of distinct opsin subclasses. However, because of the difficulty of expressing long-wavelength (LW) invertebrate opsins in vitro, our understanding of the molecular basis of functional shifts in opsin spectral sensitivities has been biased toward research primarily in vertebrates. This has restricted our ability to address whether invertebrate Gq protein-coupled opsins function in a novel or convergent way compared to vertebrate Gt opsins. Here we develop a robust heterologous expression system to purify invertebrate rhodopsins, identify specific amino acid changes responsible for adaptive spectral tuning, and pinpoint how molecular variation in invertebrate opsins underlie wavelength sensitivity shifts that enhance visual perception. By combining functional and optophysiological approaches, we disentangle the relative contributions of lateral filtering pigments from red-shifted LW and blue short-wavelength opsins expressed in distinct photoreceptor cells of individual ommatidia. We use in situ hybridization to visualize six ommatidial classes in the compound eye of a lycaenid butterfly with a four-opsin visual system. We show experimentally that certain key tuning residues underlying green spectral shifts in blue opsin paralogs have evolved repeatedly among short-wavelength opsin lineages. Taken together, our results demonstrate the interplay between regulatory and adaptive evolution at multiple Gq opsin loci, as well as how coordinated spectral shifts in LW and blue opsins can act together to enhance insect spectral sensitivity at blue and red wavelengths for visual performance adaptation.