Trends in Genetics最新文献

The extraordinary diversity and adaptive fit of organisms to their environment depends fundamentally on the availability of variation. While most population genetic frameworks assume that random mutations produce isotropic phenotypic variation, the distribution of variation available to natural selection is more restricted, as the distribution of phenotypic variation is affected by a range of factors in developmental systems. Here, we revisit the concept of developmental bias - the observation that the generation of phenotypic variation is biased due to the structure, character, composition, or dynamics of the developmental system - and argue that a more rigorous investigation into the role of developmental bias in the genotype-to-phenotype map will produce fundamental insights into evolutionary processes, with potentially important consequences on the relation between micro- and macro-evolution. We discuss the hierarchical relationships between different types of variational biases, including mutation bias and developmental bias, and their roles in shaping the realized phenotypic space. Furthermore, we highlight the challenges in studying variational bias and propose potential approaches to identify developmental bias using modern tools.

In many multicellular eukaryotes, heteromorphic sex chromosomes are responsible for determining the sexual characteristics and reproductive functions of individuals. Sex chromosomes can cause a dosage imbalance between sexes, which in some species is re-equilibrated by dosage compensation (DC). Recent genomic advances have extended our understanding of DC mechanisms in insects beyond model organisms such as Drosophila melanogaster. We review current knowledge of insect DC, focusing on its conservation and divergence across orders, the evolutionary dynamics of neo-sex chromosomes, and the diversity of molecular mechanisms. We propose a framework to uncover DC regulators in non-model insects that relies on integrating evolutionary, genomic, and functional approaches. This comprehensive approach will facilitate a deeper understanding of the evolution and essentiality of gene regulatory mechanisms.

Crossing over between homologous chromosomes in meiosis is essential in most eukaryotes to produce gametes with the correct ploidy. Meiotic crossovers are typically evenly spaced, with each homolog pair receiving at least one crossover. The association of crossovers with distal sister chromatid cohesion is critical for the proper segregation of homologs in the first meiotic division. Studies in baker's yeast (Saccharomyces cerevisiae) have shown that meiotic crossovers result primarily from the biased resolution of double Holliday junction (dHJ) recombination intermediates through the actions of factors that belong to the DNA mismatch repair family. These findings and studies involving fine-scale mapping of meiotic crossover events have led to a new generation of mechanistic models for crossing over that are currently being tested.

The increasing prevalence of genome sequencing and assembly has uncovered evidence of hyperdivergent genomic regions - loci with excess genetic diversity - in species across the tree of life. Hyperdivergent regions are often enriched for genes that mediate environmental responses, such as immunity, parasitism, and sensory perception. Especially in self-fertilizing species where the majority of the genome is homozygous, the existence of hyperdivergent regions might imply the historical action of evolutionary forces such as introgression and/or balancing selection. We anticipate that the application of new sequencing technologies, broader taxonomic sampling, and evolutionary modeling of hyperdivergent regions will provide insights into the mechanisms that generate and maintain genetic diversity within and between species.

Meiotic cells introduce numerous programmed DNA double-strand breaks (DSBs) into their genome to stimulate crossover recombination. DSB numbers must be high enough to ensure each homologous chromosome pair receives the obligate crossover required for accurate meiotic chromosome segregation. However, every DSB also increases the risk of aberrant or incomplete DNA repair, and thus genome instability. To mitigate these risks, meiotic cells have evolved an intricate network of controls that modulates the timing, levels, and genomic location of meiotic DSBs. This Review summarizes our current understanding of these controls with a particular focus on the mechanisms that prevent meiotic DSB formation at the wrong time or place, thereby guarding the genome from potentially catastrophic meiotic errors.

Transposable elements (TEs) shape every aspect of genome biology, influencing genome stability, size, and organismal fitness. Following the 2007 discovery of the piRNA defense system, researchers have made numerous findings about organisms' defenses against these genomic invaders. TEs are suppressed by a 'genomic immune system', where TE insertions within specialized regions called PIWI-interacting RNA (piRNA) clusters produce small RNAs responsible for their suppression. The evolution of piRNA clusters and the piRNA system is only now being understood, largely because most research has been conducted in developmental biology labs using only one to two genotypes of Drosophila melanogaster. While piRNAs themselves were identified simultaneously in various organisms (flies, mice, rats, and zebrafish) in 2006-2007, detailed work on piRNA clusters has only recently expanded beyond D. melanogaster. By studying piRNA cluster evolution in various organisms from an evolutionary perspective, we are beginning to understand more about TE suppression mechanisms and organism-TE coevolution.

Recent findings broadened the function of RNA polymerase II (Pol II) proximal promoter motifs from quantitative regulators of transcription to important determinants of transcription start site (TSS) position. These motifs are recognized by transcription factors (TFs) that we propose to term 'ruler' TFs (rTFs), such as NRF1, NF-Y, YY1, ZNF143, BANP, and members of the SP, ETS, and CRE families, sharing as a common feature a glutamine-rich (Q-rich) effector domain also enriched in valine, isoleucine, and threonine (QVIT-rich). We propose that rTFs guide TSS location by constraining the position of the pre-initiation complex (PIC) during its promoter recognition phase through a specialized, and still enigmatic, class of activation domains.

Spatial multiomics technologies have revolutionized biomedical research by enabling the simultaneous measurement of multiple omics modalities within intact tissue sections. This approach facilitates the reconstruction of 3D molecular architectures, providing unprecedented insights into complex cellular interactions and the intricate organization of biological systems, such as those underlying embryonic development.

'Epigenetics' is the process by which distinct cell types or cell states are inherited through multiple cell divisions. 'Epigenomics' refers to DNA-associated physical and functional entities including histone modifications and DNA methylation, not concepts of inheritance. Conflating epigenetics and epigenomics is confusing and causes misunderstanding of a fundamental biological process.

Recent studies have addressed the relevance of phase separation, by which membrane-less compartments are formed within the nucleus, to understand the impact of genetic variants. They highlight unsuspected links between phase separation and haploinsufficiency of transcription factors.