Search for: All records

Abstract A species tree is a central concept in evolutionary biology whereby a single branching phylogeny reflects relationships among species. However, the phylogenies of different genomic regions often differ from the species tree. Although tree discordance is widespread in phylogenomic studies, we still lack a clear understanding of how variation in phylogenetic patterns is shaped by genome biology or the extent to which discordance may compromise comparative studies. We characterized patterns of phylogenomic discordance across the murine rodents—a large and ecologically diverse group that gave rise to the laboratory mouse and rat model systems. Combining recently published linked-read genome assemblies for seven murine species with other available rodent genomes, we first used ultraconserved elements (UCEs) to infer a robust time-calibrated species tree. We then used whole genomes to examine finer-scale patterns of discordance across ∼12 million years of divergence. We found that proximate chromosomal regions tended to have more similar phylogenetic histories. There was no clear relationship between local tree similarity and recombination rates in house mice, but we did observe a correlation between recombination rates and average similarity to the species tree. We also detected a strong influence of linked selection whereby purifying selection at UCEs led to appreciably less discordance. Finally, we show that assuming a single species tree can result in substantial deviation from the results with gene trees when testing for positive selection under different models. Collectively, our results highlight the complex relationship between phylogenetic inference and genome biology and underscore how failure to account for this complexity can mislead comparative genomic studies. 

ABSTRACT The mechanical environment of a cell can have many effects, but whether it impacts the DNA sequence of a cell has remained unexamined. To investigate this, we developed a live-cell method to measure changes in chromosome numbers. We edited constitutive genes with GFP or RFP tags on single alleles and discovered that cells that lose Chromosome reporters (ChReporters) become non-fluorescent. We applied our new tools to confined mitosis and to inhibition of the putative tumor suppressor myosin-II. We quantified compression of mitotic chromatin in vivo and demonstrated that similar compression in vitro resulted in cell death, but also rare and heritable ChReptorter loss. Myosin-II suppression rescued lethal multipolar divisions and maximized ChReporter loss during three-dimensional (3D) compression and two-dimensional (2D) lateral confinement, but not in standard 2D culture. ChReporter loss was associated with chromosome mis-segregation, rather than just the number of divisions, and loss in vitro and in mice was selected against in subsequent 2D cultures. Inhibition of the spindle assembly checkpoint (SAC) caused ChReporter loss in 2D culture, as expected, but not during 3D compression, suggesting a SAC perturbation. Thus, ChReporters enable diverse studies of viable genetic changes, and show that confinement and myosin-II affect DNA sequence and mechano-evolution.