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Goldstein, G.

Publications and source records attributed to Goldstein, G..

3 recordsLinked to original sources

Meiotic Sex Chromosome Inactivation: conservation across the Drosophila genus

The inherent difference between sex chromosomes in males and females drives conflicts in gene expression, leading to adaptations such as Meiotic Sex Chromosome Inactivation (MSCI). In this study, we explore the evolutionary dynamics of MSCI within the Drosophila genus by analyzing transcriptomes across different stages of spermatogenesis in D. melanogaster and its progressively more distant relatives, D. simulans, D. willistoni, and D. mojavensis. Stage-specific bulk RNA sequencing, showing a strong correlation in spermatogenic gene expression patterns among these species, revealed that MSCI dates back to the early evolution of the Drosophila genus, impacting the regulation of both coding and long non-coding RNAs. Notably, for newly evolved genes, X-linked genes show higher expression levels than autosomal genes during mitosis and meiosis, indicating that MSCI predominantly regulates older genes. In contrast, newly evolved autosomal genes exhibit a gradual increase in expression throughout spermatogenesis, reaching their peak in the post-meiotic phase. During this phase, the expression of X-linked new genes decreases, eventually aligning with that of autosomal genes. This expression pattern suggests that haploid selection plays a crucial role in the regulation of new genes, with monoallelic expression of the X chromosome providing an advantage across all stages of germline development, while autosomal gene expression gains a selective edge primarily in the post-meiotic phase. Together, these findings provide new insights into the evolution of sex chromosomes and highlight the critical role of MSCI in shaping gene expression profiles in Drosophila.

genetics↗

Hunger alters approach-avoidance behaviours differently in male and female mice

BackgroundThe decision about whether to approach or avoid a reward while under threat requires balancing competing demands. Sex-specific prioritisations (e.g. mating, maternal care), or generalised prioritisations (e.g. feeding, drinking, sleeping) may differently influence approach-avoidance behaviours based on the level of "risk" and homeostatic need state of the organism. However, given known sex differences in key aspects that may influence this behaviour, direct comparison of how male and female mice make decisions to approach or avoid a dangerous area while in a fasted state have yet to be conducted. MethodsWe conducted several approach-avoidance tasks with varied levels of risk and reward in male and female mice that were either fasted or sated (fed). Mice underwent a light-dark box, elevated plus maze, baited large open field and runway task to assess their approach and avoidance behaviour. ResultIn the light-dark box and elevated plus maze, when no reward was available, fasted female mice showed greater approach behaviours than male counterparts. In the baited large open field, when reward was available, both sexes showed increased approach behaviours when fasted. However, when sated, male mice conversely showed greater approach behaviours compared to sated female mice. In the runway task, while sated mice failed to learn, fasted male mice inhibited their reward consumption in response to increased shock intensity; however, fasted female mice were resistant to increased shock intensity. ConclusionsOur study identifies sex differences in decision making behaviour in mice based on satiety state across a number of approach-avoidance tasks. We highlight several nuances of these differences based on reward availability and punishment intensity. These results shine a lens on fundamental differences between the sexes in innate, survival driven behaviours that should be taken into account for future studies. Plain English summaryEveryday decision making is often accompanied by conflict - whether we make the most appropriate decision or not can be influenced by both internal and external factors. Environmental threats and physiological pressures, such as hunger, can influence decision-making processes skewing the risk/reward ratio, yet how this may differ between the sexes has not been explored in detail. Here we used several tasks that assess decision-making in mice while manipulating the levels of risk or reward. Our findings show fasted female mice are more willing to engage in "risky" behaviour compared to fed female mice when risk levels were low, and no food reward was available. However, when a food reward was available, but risk levels were low, both male and female fasted mice were more likely to engage in risky behaviour compared to fed mice. Finally, when risk levels were high and food reward was available, fasted female mice continued to engage in risky behaviour, while male fasted mice were not. Together our study identifies nuanced sex differences in how male and female mice make decisions influenced by both physiological (hunger) and environmental threats and highlight the importance of understanding fundamental differences between the sexes in behaviour. Highlights- Fasted female mice showed greater approach behaviours compared to fasted male counterparts in tasks without reward availability. - Fasted mice of both sexes displayed greater approach behaviours when a reward was available, compared to sated controls. - Fasted male mice inhibited reward consumption under increased shock intensity, whereas fasted female mice were resistant to mild foot shock.

neuroscience↗

Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition

BackgroundReverse transcribed gene copies, or retrocopies, have emerged as a major source of evolutionary novelties. MicroRNAs (miRNAs) are small, highly conserved RNAs molecules among species that serve as key post-transcriptional regulators of gene expression. The birth and subsequent evolution of miRNAs have been addressed, but not fully. ResultsIn this study, we carried out a comprehensive investigation of miRNAs origination through retroduplicated mRNA sequences (retrocopies). We identified 17 retroduplicated miRNAs (retro-miRs) that emerged from mRNAs retrocopies. Four of these retro-miRs had de novo origination within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and were duplicated along with their host mRNAs. We found that retro-miRs are primates specific, including 5 retro-miRs conserved among all primates and two human-specific retro-miRs. All of the retro-miRs were expressed and had predicted and experimentally validated target genes, with the exception of miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes, such as metabolic processes, cell signaling and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs have a potential oncogenic role in cancer, targeting key cancer genes and being overexpressed in several cancer types, including Liver Hepatocellular Carcinoma and Stomach Adenocarcinoma. ConclusionOur findings demonstrate that mRNAs retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play roles in cancer.

genomics↗