Biology subjects

Alagöz, G.

Publications and source records attributed to Alagöz, G..

3 recordsLinked to original sources

bioRxiv2025

Integrating brain structure and function for the neurobiology and genetics of language

Brain structure and function have largely been studied separately in relation to the neurobiology and genetics of language. Here we used linked independent component analysis to integrate language network functional connectivity with brain volumetric and white matter structure in 32,677 UK Biobank participants, followed by analysis of behavioural, neurobiological and genetic correlates of the derived multimodal structure-function imaging components. Stronger functional connectivity between brain language areas was associated with increased volume of parts of the cerebellum and motor cortex, together with smaller ventricles and sensory parietal and occipital areas. The brain structure-function language components mediated an association between vocabulary level and polygenic scores for reading ability. We report 18 genomic loci associated with brain structure-function language components. Single-nucleotide polymorphism (SNP)-based heritability estimates for these components were 23-30%, and there was significant enrichment of heritability in primate-conserved genomic loci and fetal brain human-gained enhancer elements. This study revealed that structural correlates of functional language network connectivity extend well beyond previously defined language areas of the brain, and highlights the value of multimodal brain phenotyping for human neurogenetic discovery.

neuroscience↗

bioRxiv2025

Spatial and single-nucleus transcriptomic profile of a chimpanzee frontal pole

Chimpanzees, our closest living relatives, share a vast amount of our genetic code, with the majority of differences found in non-coding regions of the genome. Functional and gene regulatory differences drive phenotypic divergence, including the distinctive brain anatomy of humans compared to chimpanzees and other apes. However, little is known about species differences in gene expression, and how they relate to the evolution of neuroanatomy and cognition. This is primarily due to the limited availability of great ape brain samples and challenges in comparative spatial transcriptomic studies. Here, we present the first spatial transcriptomic data from a chimpanzee brain based on post mortem tissue from an adult female, who was euthanised due to poor health. We focus on the frontal pole, a brain region that has undergone significant evolutionary changes in size and organisation since the last common ancestor of humans and chimpanzees, and is considered critical for cognitive evolution. We examined the gene expression profiles and cell-type composition of the frontal pole on the left hemisphere, including both neuronal and non-neuronal cell types across cortical layers and white matter. By integrating our spatial transcriptomic data with a publicly available single-nucleus transcriptomic dataset of the chimpanzee dorsolateral prefrontal cortex, we mapped the spatial distribution of 29 chimpanzee brain cell types. This study represents a first step towards characterisation of spatial gene regulatory differences between the brains of non-human great apes and humans. Significance statementRecent advances in spatial transcriptomics technologies provided important insights into the spatial organisation of gene expression and cell types in human and mouse brains, yet applications in non-model organisms remain limited. Here, we present the first-ever spatial transcriptomics dataset from a chimpanzee brain. We demonstrate i) the applicability of a widely used spatial transcriptomics technique to chimpanzee brain samples freshly frozen in isopentane, and ii) an end-to-end pipeline for generating good-quality spatial transcriptomics data from chimpanzee brains. Our work paves the way for future comparative spatial transcriptomics studies across human and non-human primate brains, and marks a step toward applying spatial omics methods to great ape brains.

evolutionary biology↗

bioRxiv2024

No phenotypic consequences of archaic hominin alleles in present-day humans

Advances in paleo-genetics allowed the identification of protein-coding changes arising on the lineage leading to Homo sapiens, by comparing genomes of present-day and archaic hominins. Experimental validation of the potential impact of such changes has so far been restricted to functional assays and model organisms. Large-scale biobanking now makes it possible to identify present-day carriers of archaic alleles and to directly assess phenotypic consequences in living adults. We queried exomes of half a million people in the UK Biobank at 37 genomic positions with supposedly fixed human-specific protein-coding changes. This yielded 103 carriers at 17 positions, with variable allele counts across ancestries. Contrasting carriers and non-carriers of an exemplary archaic allele in SSH2, we observed no deviation from the norm in a range of health, psychological, and cognitive traits. We also identified 62 archaic-allele carriers for a TKTL1 missense change, previously shown to have large effects on cortical neurogenesis in brain organoids and animal models. Carriers did not show differences in relevant anatomical brain measures, and a substantial proportion had college/university degrees. This work offers an empirical demonstration of how large-scale biobank investigations of living adults can transform our understanding of human evolution. The findings challenge the notion of fixed human-specific genomic changes, highlight that individual interrogation of relevant sites is unlikely to yield major insights into the emergence of complex human traits, and emphasise the importance of including diverse ancestries when investigating origins of our species.

genetics↗