A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens.

Changes in gene regulatory elements play critical roles in human phenotypic divergence. However, identifying the base-pair changes responsible for the distinctive morphology of Homo sapiens remains challenging. Here, we report a noncoding single-nucleotide polymorphism (SNP), rs41298798, as a potential causal variant contributing to the morphology of the skull base and vertebral structures found in Homo sapiens. Screening for differentially regulated genes between Homo sapiens and extinct relatives revealed 13 candidate genes associated with basicranial development, with TBX1, implicated in DiGeorge syndrome, playing a pivotal role. Epigenetic markers and in silico analyses prioritized rs41298798 within a TBX1 intron for functional validation. CRISPR editing revealed that the 41-base-pair region surrounding rs41298798 modulates gene expression at 22q11.21. The derived allele of rs41298798 acts as an allele-specific enhancer mediated by E2F1, resulting in increased TBX1 expression levels compared to the ancestral allele. Tbx1-knockout mice exhibited skull base and vertebral abnormalities similar to those seen in DiGeorge syndrome. Phenotypic differences associated with TBX1 deficiency are observed between Homo sapiens and Neanderthals (Homo neanderthalensis). In conclusion, the regulatory divergence of TBX1 contributes to the formation of skull base and vertebral structures found in Homo sapiens.

What made us "hunter-gatherers of words".

This paper makes three interconnected claims: (i) the "human condition" cannot be captured by evolutionary narratives that reduce it to a recent 'cognitive modernity', nor by narratives that eliminates all cognitive differences between us and out closest extinct relatives, (ii) signals from paleogenomics, especially coming from deserts of introgression but also from signatures of positive selection, point to the importance of mutations that impact neurodevelopment, plausibly leading to temperamental differences, which may impact cultural evolutionary trajectories in specific ways, and (iii) these trajectories are expected to affect the language phenotypes, modifying what is being learned and how it is put to use. In particular, I hypothesize that these different trajectories influence the development of symbolic systems, the flexible ways in which symbols combine, and the size and configurations of the communities in which these systems are put to use.

What is simple is actually quite complex: A critical note on terminology in the domain of language and communication.

On the surface, the fields of animal communication and human linguistics have arrived at conflicting theories and conclusions with respect to the effect of social complexity on communicative complexity. For example, an increase in group size is argued to have opposite consequences on human versus animal communication systems: although an increase in human community size leads to some types of language simplification, an increase in animal group size leads to an increase in signal complexity. But do human and animal communication systems really show such a fundamental discrepancy? Our key message is that the tension between these two adjacent fields is the result of (a) a focus on different levels of analysis (namely, signal variation or grammar-like rules) and (b) an inconsistent use of terminology (namely, the terms "simple" and "complex"). By disentangling and clarifying these terms with respect to different measures of communicative complexity, we show that although animal and human communication systems indeed show some contradictory effects with respect to signal variability, they actually display essentially the same patterns with respect to grammar-like structure. This is despite the fact that the definitions of complexity and simplicity are actually aligned for signal variability, but diverge for grammatical structure. We conclude by advocating for the use of more objective and descriptive terms instead of terms such as "complexity," which can be applied uniformly for human and animal communication systems-leading to comparable descriptions of findings across species and promoting a more productive dialogue between fields. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Moving beyond domain-specific versus domain-general options in cognitive neuroscience.

Comparative research on language, music, and action in cognitive neuroscience keeps finding evidence for both shared and non-shared components of cognitive systems. The discussions, then, tend to quickly fall into the sterile dichotomy between domain-specific versus domain-general options. In this position paper, we take issue with this dichotomy and argue for an alternative account based on neural reuse theories to understand findings on the relationship between language, music, and action. We argue that the differences between those cognitive systems can be explained in terms of the specialization of the same brain mechanism(s) for each domain, which emerges in the course of development and/or evolution.

Temporal mapping of derived high-frequency gene variants supports the mosaic nature of the evolution of Homo sapiens.

Large-scale estimations of the time of emergence of variants are essential to examine hypotheses concerning human evolution with precision. Using an open repository of genetic variant age estimations, we offer here a temporal evaluation of various evolutionarily relevant datasets, such as Homo sapiens-specific variants, high-frequency variants found in genetic windows under positive selection, introgressed variants from extinct human species, as well as putative regulatory variants specific to various brain regions. We find a recurrent bimodal distribution of high-frequency variants, but also evidence for specific enrichments of gene categories in distinct time windows, pointing to different periods of phenotypic changes, resulting in a mosaic. With a temporal classification of genetic mutations in hand, we then applied a machine learning tool to predict what genes have changed more in certain time windows, and which tissues these genes may have impacted more. Overall, we provide a fine-grained temporal mapping of derived variants in Homo sapiens that helps to illuminate the intricate evolutionary history of our species.

Oxytocin and vasotocin receptor variation and the evolution of human prosociality.

Modern human lifestyle strongly depends on complex social traits like empathy, tolerance and cooperation. These diverse facets of social cognition have been associated with variation in the oxytocin receptor (OTR) and its sister genes, the vasotocin/vasopressin receptors (VTR1A/AVPR1A and AVPR1B/VTR1B). Here, we compared the available genomic sequences of these receptors between modern humans, archaic humans, and 12 non-human primate species, and identified sites that show heterozygous variation in modern humans and archaic humans distinct from variation in other primates, and for which we could find association studies with clinical implications. On these sites, we performed a range of analyses (variant clustering, pathogenicity prediction, regulation, linkage disequilibrium frequency), and reviewed the literature on selection data in different modern-human populations. We found five sites with modern human specific variation, where the modern human allele is the major allele in the global population (OTR: rs1042778, rs237885, rs6770632; VTR1A: rs10877969; VTR1B: rs33985287). Among them, variation in the OTR-rs6770632 site was predicted to be the most functional. Two alleles (OTR: rs59190448 and rs237888) present only in modern humans and archaic humans were putatively under positive selection in modern humans, with rs237888 predicted to be a highly functional site. Three sites showed convergent evolution between modern humans and bonobos (OTR: rs2228485 and rs237897; VTR1A: rs1042615), with OTR-rs2228485 ranking highly in terms of functionality and reported to be under balancing selection in modern humans (Schaschl, 2015) [1]. Our findings have implications for understanding hominid prosociality, as well as the similarities between modern human and bonobo social behavior.

Brain region-specific effects of nearly fixed sapiens-derived alleles.

The availability of high-coverage genomes of our extinct relatives, the Neanderthals and Denisovans, and the emergence of large, tissue-specific databases of modern human genetic variation, offer the possibility of probing the effects of modern-derived alleles in specific tissues, such as the brain, and its specific regions. While previous research has explored the effects of introgressed variants in gene expression, the effects of Homo sapiens-specific gene expression variability are still understudied. Here we identify derived, Homo sapiens-specific high-frequency (≥90%) alleles that are associated with differential gene expression across 15 brain structures derived from the GTEx database. We show that regulation by these derived variants targets regions under positive selection more often than expected by chance, and that high-frequency derived alleles lie in functional categories related to transcriptional regulation. Our results highlight the role of these variants in gene regulation in specific regions like the cerebellum and pituitary.

A Brain Region-Specific Expression Profile for Genes Within Large Introgression Deserts and Under Positive Selection in Homo sapiens.

Analyses of ancient DNA from extinct hominins have provided unique insights into the complex evolutionary history of Homo sapiens, intricately related to that of the Neanderthals and the Denisovans as revealed by several instances of admixture events. These analyses have also allowed the identification of introgression deserts: genomic regions in our species that are depleted of "archaic" haplotypes. The presence of genes like FOXP2 in these deserts has been taken to be suggestive of brain-related functional differences between Homo species. Here, we seek a deeper characterization of these regions and the specific expression trajectories of genes within them, taking into account signals of positive selection in our lineage. Analyzing publicly available transcriptomic data from the human brain at different developmental stages, we found that structures outside the cerebral neocortex, in particular the cerebellum, the striatum and the mediodorsal nucleus of the thalamus show the most divergent transcriptomic profiles when considering genes within large introgression deserts and under positive selection.

Pathway-specific effects of ADSL deficiency on neurodevelopment.

Adenylosuccinate lyase (ADSL) functions in de novo purine synthesis (DNPS) and the purine nucleotide cycle. ADSL deficiency (ADSLD) causes numerous neurodevelopmental pathologies, including microcephaly and autism spectrum disorder. ADSLD patients have normal serum purine nucleotide levels but exhibit accumulation of dephosphorylated ADSL substrates, S-Ado, and SAICAr, the latter being implicated in neurotoxic effects through unknown mechanisms. We examined the phenotypic effects of ADSL depletion in human cells and their relation to phenotypic outcomes. Using specific interventions to compensate for reduced purine levels or modulate SAICAr accumulation, we found that diminished AMP levels resulted in increased DNA damage signaling and cell cycle delays, while primary ciliogenesis was impaired specifically by loss of ADSL or administration of SAICAr. ADSL-deficient chicken and zebrafish embryos displayed impaired neurogenesis and microcephaly. Neuroprogenitor attrition in zebrafish embryos was rescued by pharmacological inhibition of DNPS, but not increased nucleotide concentration. Zebrafish also displayed phenotypes commonly linked to ciliopathies. Our results suggest that both reduced purine levels and impaired DNPS contribute to neurodevelopmental pathology in ADSLD and that defective ciliogenesis may influence the ADSLD phenotypic spectrum.

Age Effects Aggressive Behavior: RNA-Seq Analysis in Cattle with Implications for Studying Neoteny Under Domestication.

The reactive type of aggression is regulated mostly by the brain's prefrontal cortex; however, the molecular changes underlying aggressiveness in adults have not been fully characterized. We used an RNA-seq approach to investigate differential gene expression in the prefrontal cortex of bovines from the aggressive Lidia breed at different ages: young three-year old and adult four-year-old bulls. A total of 50 up and 193 down-regulated genes in the adult group were identified. Furthermore, a cross-species comparative analysis retrieved 29 genes in common with previous studies on aggressive behaviors, representing an above-chance overlap with the differentially expressed genes in adult bulls. We detected changes in the regulation of networks such as synaptogenesis, involved in maintenance and refinement of synapses, and the glutamate receptor pathway, which acts as excitatory driver in aggressive responses. The reduced reactive aggression typical of domestication has been proposed to form part of a retention of juvenile traits as adults (neoteny).

Oxytocin variation and brain region-specific gene expression in a domesticated avian species.

The Bengalese finch was domesticated more than 250 years ago from the wild white-rumped munia (WRM). Similar to other domesticated species, Bengalese finches show a reduced fear response and have lower corticosterone levels, compared to WRMs. Bengalese finches and munias also have different song types. Since oxytocin (OT) has been found to be involved in stress coping and auditory processing, we tested whether the OT sequence and brain expression pattern and content differ in wild munias and domesticated Bengalese finches. We sequenced the OT from 10 wild munias and 11 Bengalese finches and identified intra-strain variability in both the untranslated and protein-coding regions of the sequence, with all the latter giving rise to synonymous mutations. Several of these changes fall in specific transcription factor-binding sites, and show either a conserved or a relaxed evolutionary trend in the avian lineage, and in vertebrates in general. Although in situ hybridization in several hypothalamic nuclei did not reveal significant differences in the number of cells expressing OT between the two strains, real-time quantitative PCR showed a significantly higher OT mRNA expression in the cerebrum of the Bengalese finches relative to munias, but a significantly lower expression in their diencephalon. Our study thus points to a brain region-specific pattern of neurochemical expression in domesticated and wild avian strains, which could be linked to domestication and the behavioral changes associated with it.

Why musical hierarchies?

Credible signaling may have provided a selection pressure for producing and discriminating increasingly elaborate proto-musical signals. But, why evolve them to have hierarchical structure? We argue that the hierarchality of tonality and meter is a byproduct of domain-general mechanisms evolved for reasons other than credible signaling.

Hierarchical control as a shared neurocognitive mechanism for language and music.

Although comparative research has made substantial progress in clarifying the relationship between language and music as neurocognitive systems from both a theoretical and empirical perspective, there is still no consensus about which mechanisms, if any, are shared and how they bring about different neurocognitive systems. In this paper, we tackle these two questions by focusing on hierarchical control as a neurocognitive mechanism underlying syntax in language and music. We put forward the Coordinated Hierarchical Control (CHC) hypothesis: linguistic and musical syntax rely on hierarchical control, but engage this shared mechanism differently depending on the current control demand. While linguistic syntax preferably engages the abstract rule-based control circuit, musical syntax rather employs the coordination of the abstract rule-based and the more concrete motor-based control circuits. We provide evidence for our hypothesis by reviewing neuroimaging as well as neuropsychological studies on linguistic and musical syntax. The CHC hypothesis makes a set of novel testable predictions to guide future work on the relationship between language and music.

Capturing the Effects of Domestication on Vocal Learning Complexity.

Domesticated and vocal learning species can serve as informative model organisms for the reduction of reactive aggression and emergence of speech in our lineage. Amidst mounting evidence that domestication modifies vocal repertoires across different species, we focus on the domesticated Bengalese finch, which has a more complex song than the wild-type white-rumped munia. Our explanation for this effect revolves around the glutamate neurotransmitter system. Glutamate signaling (i) is implicated in birdsong learning, (ii) controls dopamine activity in neural circuits crucial for vocal learning, (iii) is disproportionately targeted in the evolution of domesticates, and (iv) regulates stress responses and aggressive behaviors attenuated under domestication. We propose that attenuated excitation of stress-related neural circuits potentiates vocal learning via altered dopaminergic signaling.

Universal nomenclature for oxytocin-vasotocin ligand and receptor families.

Oxytocin (OXT; hereafter OT) and arginine vasopressin or vasotocin (AVP or VT; hereafter VT) are neurotransmitter ligands that function through specific receptors to control diverse functions1,2. Here we performed genomic analyses on 35 species that span all major vertebrate lineages, including newly generated high-contiguity assemblies from the Vertebrate Genomes Project3,4. Our findings support the claim5 that OT (also known as OXT) and VT (also known as AVP) are adjacent paralogous genes that have resulted from a local duplication, which we infer was through DNA transposable elements near the origin of vertebrates and in which VT retained more of the parental sequence. We identified six major oxytocin-vasotocin receptors among vertebrates. We propose that all six of these receptors arose from a single receptor that was shared with the common ancestor of invertebrates, through a combination of whole-genome and large segmental duplications. We propose a universal nomenclature based on evolutionary relationships for the genes that encode these receptors, in which the genes are given the same orthologous names across vertebrates and paralogous names relative to each other. This nomenclature avoids confusion due to differential naming in the pre-genomic era and incomplete genome assemblies, furthers our understanding of the evolution of these genes, aids in the translation of findings across species and serves as a model for other gene families.

Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle.

BACKGROUND: Aggressive behavior is an ancient and conserved trait, habitual for most animals in order to eat, protect themselves, compete for mating and defend their territories. Genetic factors have been shown to play an important role in the development of aggression both in animals and humans, displaying moderate to high heritability estimates. Although such types of behaviors have been studied in different animal models, the molecular architecture of aggressiveness remains poorly understood. This study compared gene expression profiles of 16 prefrontal cortex (PFC) samples from aggressive and non-aggressive cattle breeds: Lidia, selected for agonistic responses, and Wagyu, selected for tameness. RESULTS: A total of 918 up-regulated and 278 down-regulated differentially expressed genes (DEG) were identified, representing above-chance overlap with genes previously identified in studies of aggression across species, as well as those implicated in recent human evolution. The functional interpretation of the up-regulated genes in the aggressive cohort revealed enrichment of pathways such as Alzheimer disease-presenilin, integrins and the ERK/MAPK signaling cascade, all implicated in the development of abnormal aggressive behaviors and neurophysiological disorders. Moreover, gonadotropins, are up-regulated as natural mechanisms enhancing aggression. Concomitantly, heterotrimeric G-protein pathways, associated with low reactivity mental states, and the GAD2 gene, a repressor of agonistic reactions associated with PFC activity, are down-regulated, promoting the development of the aggressive responses selected for in Lidia cattle. We also identified six upstream regulators, whose functional activity fits with the etiology of abnormal behavioral responses associated with aggression. CONCLUSIONS: These transcriptional correlates of aggression, resulting, at least in part, from controlled artificial selection, can provide valuable insights into the complex architecture that underlies naturally developed agonistic behaviors. This analysis constitutes a first important step towards the identification of the genes and metabolic pathways that promote aggression in cattle and, providing a novel model species to disentangle the mechanisms underlying variability in aggressive behavior.

Modern human changes in regulatory regions implicated in cortical development.

BACKGROUND: Recent paleogenomic studies have highlighted a very small set of proteins carrying modern human-specific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to identify derived regulatory changes in the modern human lineage in comparison to Neanderthals/Denisovans. We report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes and are active at early stages of cortical development. RESULTS: We identified 212 genes controlled by regulatory regions harboring modern human changes where Neanderthals/Denisovans carry the ancestral allele. These regulatory regions significantly overlap with putative modern human positively-selected regions and schizophrenia-related genetic loci. Among the 212 genes, we identified a substantial proportion of genes related to transcriptional regulation and, specifically, an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT signaling for the generation and proliferation of intermediate progenitor cells. CONCLUSIONS: This study complements previous research focused on protein-coding changes distinguishing our species from Neanderthals/Denisovans and highlights chromatin regulation as a functional category so far overlooked in modern human evolution studies. We present a set of candidates that will help to illuminate the investigation of modern human-specific ontogenetic trajectories.

Vocal learning: Beyond the continuum.

Vocal learning is the ability to modify vocal output on the basis of experience. Traditionally, species have been classified as either displaying or lacking this ability. A recent proposal, the vocal learning continuum, recognizes the need to have a more nuanced view of this phenotype and abandon the yes-no dichotomy. However, it also limits vocal learning to production of novel calls through imitation, moreover subserved by a forebrain-to-phonatory-muscles circuit. We discuss its limitations regarding the characterization of vocal learning across species and argue for a more permissive view.

Evolutionary Dynamics Do Not Motivate a Single-Mutant Theory of Human Language.

One of the most controversial hypotheses in cognitive science is the Chomskyan evolutionary conjecture that language arose instantaneously in humans through a single mutation. Here we analyze the evolutionary dynamics implied by this hypothesis, which has never been formalized before. The hypothesis supposes the emergence and fixation of a single mutant (capable of the syntactic operation Merge) during a narrow historical window as a result of frequency-independent selection under a huge fitness advantage in a population of an effective size no larger than ~15 000 individuals. We examine this proposal by combining diffusion analysis and extreme value theory to derive a probabilistic formulation of its dynamics. We find that although a macro-mutation is much more likely to go to fixation if it occurs, it is much more unlikely a priori than multiple mutations with smaller fitness effects. The most likely scenario is therefore one where a medium number of mutations with medium fitness effects accumulate. This precise analysis of the probability of mutations occurring and going to fixation has not been done previously in the context of the evolution of language. Our results cast doubt on any suggestion that evolutionary reasoning provides an independent rationale for a single-mutant theory of language.