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Although synonymous mutations are commonly assumed neutral or nearly so, recent years have seen reports of fitness effects of synonymous mutations detected under laboratory conditions. In a previous study, we used genome editing to construct thousands of yeast mutants each carrying a synonymous or nonsynonymous mutation in one of 21 genes, and discovered that most synonymous and most nonsynonymous mutations are deleterious. A concern was raised that this observation could be caused by the fitness effects of potential CRISPR/Cas9 off-target edits and/or secondary mutations, and an experiment that would be refractory to such effects was proposed. Using genome sequencing, we here show that no CRISPR/Cas9 off-target editing occurred, although some mutants did carry secondary mutations. Analysis of mutants with negligible effects from secondary mutations and new data collected from the proposed experiment confirms the original conclusion. These findings, along with other reports of fitness effects of synonymous mutations from both case and systematic studies, necessitate a paradigm shift from assuming (near) neutrality of synonymous mutations. [ABSTRACT FROM AUTHOR]

The human sex ratio (fraction of males) at birth is close to 0.5 at the population level, an observation commonly explained by Fisher's principle. However, past human studies yielded conflicting results regarding the existence of sex ratio-influencing mutations—a prerequisite to Fisher's principle, raising the question of whether the nearly even population sex ratio is instead dictated by the random X/Y chromosome segregation in male meiosis. Here we show that, because a person's offspring sex ratio (OSR) has an enormous measurement error, a gigantic sample is required to detect OSR-influencing genetic variants. Conducting a UK Biobank-based genome-wide association study that is more powerful than previous studies, we detect an OSR-associated genetic variant, which awaits verification in independent samples. Given the abysmal precision in measuring OSR, it is unsurprising that the estimated heritability of OSR is effectively zero. We further show that OSR's estimated heritability would remain virtually zero even if OSR is as genetically variable as the highly heritable human standing height. These analyses, along with simulations of human sex ratio evolution under selection, demonstrate the compatibility of the observed genetic architecture of human OSR with Fisher's principle and render it plausible that multiple OSR-influencing genetic variants segregate among humans. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

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.

Background: To explore the clinical efficacy of traditional Chinese medicine decoction combined with recombinant human interferon α 2b 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 α 2b, 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 α 2b 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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Siliang Song et al.)