Cold Spring Harbor Perspectives in Biology

The concept of "genetic coupling" in mate recognition systems arose in the 1960s as a potential mechanism to maintain coordination between signals and receivers during evolutionary divergence. At its most basic it proposed that the same genes might influence trait and preference, and therefore mutations could result in coordinated changes in both traits. Since then, the concept has expanded in scope and is often used to include linkage or genetic correlation between recognition system components. Here we review evidence for genetic coupling, concentrating on proposed examples of a common genetic basis for signals and preferences...

Lipids are the defining features of cellular membranes. They act collectively to form a variety of different structures, and understanding their complex behavior represents an early example of systems biology. A multidisciplinary approach is needed to analyse the functions of lipids in biological systems, and new work is providing fascinating insights into their roles in membrane biology, metabolism, signaling, subcellular dynamics and various disease processes.

Synapses are specialized intercellular junctions connecting pre- and postsynaptic neurons into functional neural circuits. Synaptic cell adhesion molecules (CAMs) constitute key players in synapse development that engage in homo- or heterophilic interactions across the synaptic cleft. Decades of research have identified numerous synaptic CAMs, mapped their trans- synaptic interactions, and determined their role in orchestrating synaptic connectivity. However, surprisingly little is known about the molecular mechanisms that translate trans -synaptic adhesion into the assembly of pre- and postsynaptic compartments...

The recent CASP15 competition highlighted the critical role of multiple sequence alignments (MSAs) in protein structure prediction, as demonstrated by the success of the top AlphaFold2-based prediction methods. To push the boundaries of MSA utilization, we conducted a petabase-scale search of the Sequence Read Archive (SRA), resulting in gigabytes of aligned homologs for CASP15 targets. These were merged with default MSAs produced by ColabFold-search and provided to ColabFold-predict. By using SRA data, we achieved highly accurate predictions (GDT_TS > 70) for 66% of the non-easy targets, whereas using ColabFold-search default MSAs scored highly in only 52%...

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is a heterogeneous spectrum of potential changes that occur in a context-specific manner. These changes are determined by diverse signaling events and vary not only with the nature and severity of different CNS insults but also with location in the CNS, genetic predispositions, age, and potentially also with "molecular memory" of previous reactivity events...

Astrocytes play an important role in controlling microvascular diameter and regulating local cerebral blood flow (CBF) in several physiological and pathological scenarios. Neurotransmitters released from active neurons evoke Ca2+ increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid (AA) from astrocyte endfeet. Synthesis of prostaglandin E2 (PGE2 ) and epoxyeicosatrienoic acids (EETs) dilate blood vessels while 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels...

The inability of the mammalian central nervous system (CNS) to undergo spontaneous regeneration has long been regarded as a central tenet of neurobiology. However, while this is largely true of the neuronal elements of the adult mammalian CNS, save for discrete populations of granule neurons, the same is not true of its glial elements. In particular, the loss of oligodendrocytes, which results in demyelination, triggers a spontaneous and often highly efficient regenerative response, remyelination, in which new oligodendrocytes are generated and myelin sheaths are restored to denuded axons...

Speciation often involves the evolution of multiple genetic-based barriers to gene flow (i.e., "coupling"). However, barriers may exhibit a diversity of evolutionary interactions during speciation. These dynamics are important in reinforcement, where selection may favor different prezygotic isolating barriers to avoid maladaptive hybridization. Here we study the interaction between evolution of sexual and habitat isolation. We first review the empirical literature where both barriers were explicitly considered, and then develop a population genetic model of reinforcement...

The study of neural development is usually concerned with the question of how nervous systems get put together. Variation in these processes is usually of interest as a means of revealing these normative mechanisms. However, variation itself can be an object of study and is of interest from multiple angles. First, the nature of variation in both the processes and the outcomes of neural development is relevant to our understanding of how these processes and outcomes are encoded in the genome. Second, variation in the wiring of the brain in humans may underlie variation in all kinds of psychological and behavioral traits, as well as neurodevelopmental disorders...

This is a review of inherited and acquired causes of human demyelinating neuropathies and a subset of disorders that affect axon-Schwann cell interactions. Nearly all inherited demyelinating neuropathies are caused by mutations in genes that are expressed by myelinating Schwann cells, affecting diverse functions in a cell-autonomous manner. The most common acquired demyelinating neuropathies are Guillain-Barré syndrome and chronic, inflammatory demyelinating polyneuropathy, both of which are immune-mediated...

Lipids are characterized by extremely high structural diversity translated into a wide range of physicochemical properties. As such, lipids are vital for many different functions including organization of cellular and organelle membranes, control of cellular and organismal energy metabolism, as well as mediating multiple signaling pathways. To maintain the lipid chemical diversity and to achieve rapid lipid remodeling required for the responsiveness and adaptability of cellular membranes, living systems make use of a network of chemical modifications of already existing lipids that complement the rather slow biosynthetic pathways...

Interactions between alleles and across environments play an important role in the fitness of hybrids and are at the heart of the speciation process. Fitness landscapes capture these interactions and can be used to model hybrid fitness, helping us to interpret empirical observations and clarify verbal models. Here, we review recent progress in understanding hybridization outcomes through Fisher's geometric model, an intuitive and analytically tractable fitness landscape that captures many fitness patterns observed across taxa...

The endoplasmic reticulum (ER) is the key organelle for membrane biogenesis. Most lipids are synthesized in the ER, and most membrane proteins are first inserted into the ER membrane before they are transported to their target organelle. The composition and properties of the ER membrane must be carefully controlled to provide a suitable environment for the insertion and folding of membrane proteins. The unfolded protein response (UPR) is a powerful signaling pathway that balances protein and lipid production in the ER...

Peripheral nerves exist in a stable state in adulthood providing a rapid bidirectional signaling system to control tissue structure and function. However, following injury, peripheral nerves can regenerate much more effectively than those of the central nervous system (CNS). This multicellular process is coordinated by peripheral glia, in particular Schwann cells, which have multiple roles in stimulating and nurturing the regrowth of damaged axons back to their targets. Aside from the repair of damaged nerves themselves, nerve regenerative processes have been linked to the repair of other tissues and de novo innervation appears important in establishing an environment conducive for the development and spread of tumors...

Coupling has emerged as a concept to describe the transition from differentiated populations to newly evolved species through the strengthening of reproductive isolation. However, the term has been used in multiple ways, and relevant processes have sometimes not been clearly distinguished. Here, we synthesize existing uses of the concept of coupling and find three main perspectives: (1) coupling as the build-up of linkage disequilibrium among loci underlying barriers to gene exchange, (2) coupling as the build-up of genome-wide linkage disequilibrium, and (3) coupling as the process generating a coincidence of distinct barrier effects...

Conscious perception in mammals depends on precise circuit connectivity between cerebral cortex and thalamus; the evolution and development of these structures are closely linked. During the wiring of reciprocal thalamus-cortex connections, thalamocortical axons (TCAs) first navigate forebrain regions that had undergone substantial evolutionary modifications. In particular, the organization of the pallial-subpallial boundary (PSPB) diverged significantly between mammals, reptiles, and birds. In mammals, transient cell populations in internal capsule and early corticofugal projections from subplate neurons closely interact with TCAs to guide pathfinding through ventral forebrain and PSPB crossing...

Glia play a crucial role in providing metabolic support to neurons across different species. To do so, glial cells isolate distinct neuronal compartments from systemic signals and selectively transport specific metabolites and ions to support neuronal development and facilitate neuronal function. Because of their function as barriers, glial cells occupy privileged positions within the nervous system and have also evolved to serve as signaling intermediaries in various contexts. The fruit fly, Drosophila melanogaster , has significantly contributed to our understanding of glial barrier development and function...

Gene editing and genetic modification hold enormous potential to deliver solutions to multiple climate change challenges. The most important rate-limiting obstacles impeding their development and deployment are not technical, but rather counterproductive policies and regulations. These are driven in part by the mistaken apprehension of widespread public opposition. These obstacles are described and solutions to overcoming them are presented.

Ecologically mediated selection against hybrids, caused by hybrid phenotypes fitting poorly into available niches, is typically viewed as distinct from selection caused by epistatic Dobzhansky-Muller hybrid incompatibilities. Here, we show how selection against transgressive phenotypes in hybrids manifests as incompatibility. After outlining our logic, we summarize current approaches for studying ecology-based selection on hybrids. We then quantitatively review QTL-mapping studies and find traits differing between parent taxa are typically polygenic...

How barriers to gene flow arise and are maintained are key questions in evolutionary biology. Speciation research has mainly focused on barriers that occur either before mating or after zygote formation. In comparison, postmating prezygotic (PMPZ) isolation-a barrier that acts after gamete release but before zygote formation-is less frequently investigated but may hold a unique role in generating biodiversity. Here we discuss the distinctive features of PMPZ isolation, including the primary drivers and molecular mechanisms underpinning PMPZ isolation...