Biology subjects

Hayakawa, T.

Publications and source records attributed to Hayakawa, T..

10 recordsLinked to original sources

bioRxiv2026

Polygenic evolution towards a morning chronotype in modern humans

Chronotype is a behavioural phenotype, and its phenotypic trend is considered to change at higher latitudes. In the current study, we performed a polygenic assessment of chronotype trend using associated single nucleotide polymorphisms identified by a genome wide-association study. We found that the phenotypic trend towards morningness increased drastically during the migration of anatomically modern humans above 20 degrees north. Furthermore, two types of latitudinal selection of morningness alleles contributed to establishing the trend towards the morning chronotype at higher latitudes. We propose that the trend towards morningness is stronger in present-day modern humans living above 20 degrees north than in Neanderthals.

evolutionary biology↗

bioRxiv2026

Genomic and phenotypic consequences of long-term isolation and small population size in Yakushima macaques

The relative roles of genetic drift, inbreeding, and natural selection in island evolution have been fundamental themes in evolutionary biology for nearly a century. However, empirical studies have yet to reach a consensus, and research integrating both genotypes and phenotypes in primates remains limited. The present study aims to estimate the demographic history of an island primate population, the Yakushima macaque (Macaca fuscata yakui), and evaluate the genomic and morphological consequences of its isolation. To this end, we conducted population genetic analyses based on whole-genome sequencing and geometric morphometric analyses of cranial shape. Our results indicate that M. f. yakui has been isolated with an effective population size of several thousand individuals for over 100,000 years. Although we detected signatures of purifying selection, deleterious alleles have not been sufficiently purged. The degree of fluctuating asymmetry in males was slightly, yet significantly, higher in M. f. yakui than in mainland populations, whereas this trend was not observed in females. Marginal evidence of directional selection was found for cranial size, but not for shape. Overall, our findings suggest that due to long-term isolation, genetic drift and inbreeding have exerted a substantial influence on shaping genotypic and phenotypic variation in this island population.

evolutionary biology↗

bioRxiv2026

Early origin of sugar sensing in jawed vertebrates

Sweet taste guides animals to consume carbohydrate-rich foods, and many different vertebrate groups, from fish to mammals, rely on sugar-rich fruits or nectar produced by flowering plants (angiosperms). Although the genes encoding T1R2-T1R3, the receptor pair that mammals use to sense sugars, exist in the genomes of many vertebrates, their functions are unclear--and whether sugar sensing arose once early in vertebrate evolution or independently in different lineages after angiosperms evolved is currently unknown. Here, we combined ancestral reconstruction and receptor functional profiling to examine the evolutionary history of T1R taste receptors--including recently-described non-canonical receptors--across all major vertebrate clades. Our results pinpoint the origin of sugar sensing to before the emergence of angiosperms and uncover a myriad of alternative T1R-based sugar-sensing mechanisms, suggesting multiple independent T1R trajectories and revealing uncharted sensory diversity across vertebrates.

evolutionary biology↗

bioRxiv2026

Age-associated erosion of organ-specific endothelial programs compromises tissue function and resilience

Endothelial cells (ECs) express organ-specific gene programs supporting tissue homeostasis and resilience. However, the mechanisms by which aging reshapes these organ-specific endothelial programs and how the resulting changes affect tissue homeostasis, resilience, and disease susceptibility remain largely unknown. Herein, we performed single-cell RNA sequencing of ECs harvested from five organs across the lifespan and found that aging progressively erodes organ-specific endothelial programs while inducing shared interferon-responsive and antigen-presentation programs across organs. Although vascular subtype identity and conserved capillary subset identity were mostly preserved, these organ-specific transcriptional programs were broadly attenuated with aging, indicating erosion of organ-specific endothelial identity to be a fundamental feature of endothelial aging. Importantly, these alterations were associated with declines in specialized EC functions, including alveolar barrier maintenance in the lung, scavenging activity in the liver, angiogenic capacity in the heart, and homeostatic programs in the kidneys and the brain, suggesting that age-related EC alterations compromise tissue homeostasis and resilience in multiple organs. Furthermore, we established a single-cell aging index for alveolar capillary ECs in mice and humans, revealing stress-associated endothelial activation to potentially be an intermediate state linking functional deterioration to cellular senescence, and also demonstrating marked heterogeneity in aging states even among ECs from animals of the same chronological age. Notably, alveolar capillary ECs exhibited progressive functional decline before reaching a senescent-like state, suggesting endothelial dysfunction to precede overt cellular senescence as the organism ages. Collectively, our findings establish progressive erosion of organ-specific endothelial programs as a central feature of vascular aging and provide a conceptual framework for elucidating how endothelial aging contributes to tissue dysfunction and reduced resilience across organs.

physiology↗

bioRxiv2024

Global adaptive evolution involved in neuroticism and educational behaviors through the spread of anatomically modern humans

A cumulative process of cultural evolution occurred globally alongside the spread of anatomically modern humans (AMHs). This process of evolution was likely accompanied by global changes in mental and behavioral phenotypes, resulting in cultural differences between AMHs and Neanderthals. Globally, selective increases of frequencies were detected in alleles, which contributed to the suppression of neuroticism and advanced learning. This finding indicates that neuroticism was suppressed and learning behaviors developed through the global spread of AMHs. It suggests that global adaptation to psychosocial stress occurred, which contributed to cumulative cultural evolution by increasing cooperative learning. A comparison of phenotypic trends at the population level indicates that such globally occurring adaptive evolution, entailing neuroticism suppression and increased learning behaviors has been more significant in AMHs than in Neanderthals. However, adaptive evolution toward greater intelligence was more significant in Neanderthals than in AMHs. These findings suggest that mental traits involved in cultural development evolved differently in AMHs and Neanderthals, and that learning behaviors such as cooperative learning, rather than intelligence, played an important role in AMH evolution.

evolutionary biology↗

bioRxiv2024

Thermostability and binding properties of single-chained Fv fragments derived from therapeutic antibodies

Small antibody fragments have recently been used as alternatives to full-length monoclonal antibodies in therapeutic applications. One of the most popular fragment antibodies is single-chain fragment variables (scFvs), consisting of variable heavy (VH) and variable light (VL) domains linked by a flexible peptide linker. scFvs have small molecular sizes, which enables good tissue penetration and low immunogenicity. Despite these advantages, the use of scFvs, especially for therapeutic purpose, is still limited because of the difficulty to regulate the binding activity and conformational stability. In this study, we constructed and analyzed 10 scFv fragments derived from 10 representatives of FDA-approved mAbs to evaluate their physicochemical properties. Differential scanning calorimetry analysis showed that scFvs exhibited relatively high but varied thermostability, from 50 to 70 {degrees}C of melting temperatures, and different unfolding cooperativity. Surface plasmon resonance analysis revealed that scFvs fragments that exhibit high stability and cooperative unfolding likely tend to maintain antigen binding. This study demonstrated the comprehensive physicochemical properties of scFvs derived from FDA-approved antibodies, providing insights into antibody design and development.

bioengineering↗

bioRxiv2023

Comparative transcriptomics shows the evolutionary origin of acoustic fat bodies through a trade-off with skull muscles in toothed whales

Toothed whales (odontocetes) have developed acoustic fat bodies, which include forehead melon, extra-mandibular fat body and intra-mandibular fat body. These contribute to the sound transmission pathways in the unique echolocation process of toothed whales. The acoustic fat bodies of Odontocetes accumulate unusual fatty acids, making them novel traits with unique functional anatomy and chemistry. This study provides new insights into the evolutionary origin and lipid utilisation of acoustic fat bodies in harbour porpoise (Phocoena phocoena) and Pacific white-sided dolphin (Lagenorhynchus obliquidens) using comparative transcriptomics. Comprehensive gene expression analyses indicated that the acoustic fat bodies of toothed whales are composites of muscle and adipose tissues, mainly composed of intramuscular fat. The extra-mandibular fat body is a homologue of the masseter muscle. Additionally, we demonstrated that gene expression-based functional enrichments for specialised branched-chain amino acid metabolism, endocytosis, lysosomes and peroxisomes contribute to the maintenance of the unique fatty characteristics of the acoustic fat bodies of toothed whales. A trade-off occurred in the evolution of acoustic fat bodies as a result of the fatty reorganisation of head muscles involved in aquatic adaptation in toothed whales.

evolutionary biology↗

bioRxiv2022

Genome assembly of the numbat (Myrmecobius fasciatus), the only termitivorous marsupial

The numbat (Myrmecobius fasciatus) is a critically endangered Australian marsupial, and the last surviving member of the Myrmecobiidae family. The numbat regularly undergoes torpor and is unique amongst marsupials as it is the only diurnal and termitivorous species. Here we sequenced the first draft genome of the numbat using 10x Genomics chromium linked-read technology, resulting in a 3.42 Gbp genome with a scaffold N50 of 223 Kbp. A global transcriptome from liver, lung and tongue was also generated to aid genome annotation with Fgenesh++, identifying 21,465 protein-coding genes and 78.7% complete mammalian BUSCOs. To investigate adaptation to the numbats termitivorous diet and arid/semi-arid range, we interrogated the most highly expressed transcripts within the tongue and manually annotated taste, vomeronasal and aquaporin gene families. Antimicrobial proteins and proteins involved in digestion were highly expressed in the tongue, as expected. Similarly, umami taste receptors were also expressed in the tongue, however sweet taste receptors were not expressed in this tissue. This pattern of taste receptor expression, combined with the putative contraction of the bitter taste receptor gene repertoire in the numbat genome, may indicate a potential evolutionary adaptation to their specialized termitivorous diet. Vomeronasal and aquaporin gene repertoires were similar to other marsupials and have not undergone expansion or contraction. The draft numbat genome is a valuable tool for conservation and can be applied to population genetics/genomics studies and to investigate the unique biology of this interesting species.

genomics↗

bioRxiv2021

Lower promoter activity of the ST8SIA2 gene has been favored in evolving human collective brains

ST8SIA2 is the main factor regulating expression of the phenotype involved in schizophrenia. Lowered promoter activity of the ST8SIA2 gene is considered to be protective against schizophrenia by conferring tolerance to psychosocial stress. Here, we examined the promoter type composition of anatomically modern humans (AMHs) and archaic humans (AHs; Neanderthals and Denisovans), and compared the promoter activity at the population level (population promoter activity; PPA) between them. In AMHs, the TCT-type, showing the second lowest promoter activity, was most prevalent in the ancestral population of non-Africans. However, the detection of only the CGT-type from AH samples and recombination tracts in AH sequences showed that the CGT- and TGT-types, exhibiting the two highest promoter activities, were common in AH populations. Furthermore, interspecies gene flow occurred into AMHs from AHs and into Denisovans from Neanderthals, influencing promoter-type compositions independently in both AMHs and AHs. The difference of promoter-type composition makes PPA unique in each population. East and Southeast Asian populations show the lowest PPA. This results from the selective increase of the CGC-type, showing the lowest promoter activity, in these populations. Every non-African population shows significantly lower PPA than African populations, resulting from the TCT-type having the highest prevalence in the ancestral population of non-Africans. In addition, PPA reduction is also found among subpopulations within Africa via a slight increase of the TCT-type. These findings indicate a trend toward lower PPA in the spread of AMHs, interpreted as a continuous adaptation to psychosocial stress arising in migration. This trend is considered as genetic tuning for the evolution of collective brains. The inferred promoter-type composition of AHs differed markedly from that of AMHs, resulting in higher PPA in AHs than in AMHs. This suggests that the trend toward lower PPA is a unique feature in AMH spread.

evolutionary biology↗

bioRxiv2019

Exome sequences of toque macaques (Macaca sinica) of Sri Lanka reveal many amino acid changes

Macaques are one of the most widely used model organisms in biomedical research. Macaca mulatta and M. fascicularis are currently being used for toxicology, HIV, diabetes, neuroscience and psychiatric and psychological disorder researches. Many studies have been conducted on M. mulatta and M. fascicularis genomes for this purpose in order to understand the genomic properties of these species. Several M. fascicularis individuals from different geographical locations and also M. mulatta genomes have been sequenced and studied in depth for the purpose of understanding the phylogenetic and evolutionary relationships between various macaque populations. But still a gap in knowledge remains for other macaque populations such as the Sinica group. In this study for the very first time, we sequenced the exome of toque macaques (M. sinica), an endemic island population of Sri Lanka. Here we confirmed that M. sinica and M. thibetana cluster together and are closely related, also the three distinct phylogenetic groupings of fascicularis and sinica. We also found that M. sinica has less number of polymorphisms with respect to the reference genome M. mulatta signifying the smaller and restricted population size of this species.

evolutionary biology↗