Biology subjects

Hukkanen, M.

Publications and source records attributed to Hukkanen, M..

11 recordsLinked to original sources

bioRxiv2026

An epigenetic palimpsest: the King penguin's blood methylome reveals conserved hematopoietic ageing

Age-associated DNA methylation is conserved across vertebrates, but whether epigenetic ageing reflects cellular ageing programmes or age-dependent shifts in cell composition remains unresolved. Here, using 126 whole-blood methylomes from known-age King penguins (Aptenodytes patagonicus), we exploit a vertebrate system in which nucleated erythrocytes dominate peripheral blood, minimizing the influence of leukocyte heterogeneity. We identify a core set of 409 ageing-associated genes showing lifelong, clock-like methylation change. These genes are strongly enriched for regulators of hematopoietic stem and progenitor cell (HSPC) function and niche communication. Integration of methylome, transcriptome and chromatin-accessibility data reveals that many of the strongest ageing signals derive from genes inactive in mature erythrocytes, consistent with the persistence of epigenetic states from ancestral hematopoietic progenitors. A comparison with methylation profiles from 1,501 humans identified a conserved cross-species subset of ageing genes, and a human epigenetic age model constructed solely from orthologues of penguin ageing genes predicts chronological age with high accuracy while remaining largely insensitive to blood cell composition. We propose that blood epigenetic ageing signatures contain a long-lived cellular memory of stem-cell ageing, that may represent an evolutionarily ancient layer of the vertebrate ageing process.

systems biology↗

bioRxiv2026

The BEAC, an epigenetic clock for birds

Epigenetic clocks are powerful tools for estimating both chronological and biological age, enabling the integration of age information into population monitoring, demographic modelling, and research on the ecophysiology and evolution of ageing. Most epigenetic clocks so far have been developed for mammals: here, we present the Bird Epigenetic Ageing Clock (BEAC) for estimating chronological age in avian species. BEAC was established based on genome-wide enzymatic methylation sequencing data of known-age king penguins (Aptenodytes patagonicus), and validated in nine other bird species. The BEAC collects age-informative signals into a bisulfite amplicon sequencing panel of 24 primer pairs, providing a highly accurate and cost-effective alternative to sequencing-intensive approaches. It achieved strong predictive performance in independent king penguin training (R{superscript 2}=0.88; MAE=1.7 years, n=78) and testing data (R{superscript 2}=0.79; MAE=2.3 years, n=41), with negligible batch effects, high longitudinal consistency, and resilience to reduced sample size or missing loci. Importantly, cross-species validation across 180 samples showed that BEAC reliably captures age-associated methylation signals in nine additional bird species across seven clades, demonstrating that a single set of loci can be predictive of ageing across multiple different bird species. BEAC offers a flexible, empirically validated tool and a transferable framework for developing epigenetic clocks in avian species, providing a highly valuable resource for eco-evolutionary studies of ageing in wild species.

molecular biology↗

bioRxiv2024

The effects of early-life ambient temperature on the gut microbiome of a wild bird? an experimental approach

Vertebrate gut microbiome has significant effects on host development, health, and fitness. Multiple external factors contribute to gut microbiome variation, and the role of ambient temperature has gained increasing attention. Yet, temperature effects are often tested in extremes and in captive systems. We experimentally studied the effect of subtle temperature decreases during post-natal development on gut microbiome diversity and composition in wild pied flycatchers (Ficedula hypoleuca). We also performed partial cross-fostering to study the relative contribution of genetic and rearing environment on microbiome. Nest-box cold treatment did not influence gut microbiome diversity or composition, which may be due to the small temperature change, ontogenetic stage, or other factors, such as diet, causing large variation in the data. Rearing environment explained more of the variation in gut microbiome than genetic background, but the variance explained was relatively small. Future studies need to further address the drivers of the large intraspecific variation in microbiome in natural populations.

ecology↗

bioRxiv2024

Sedentary life accelerates epigenetic ageing in King penguins

Introductory paragraphAdvances in medicine and food security have contributed to an increase in human lifespan1. Yet, the associated rise in sedentary behaviour and in obesity2,3 already threatens these gains4. Indeed, a growing body of evidence supports the central role of nutrient sensing and energy management pathways in regulating ageing rate and healthspan5,6, but the diversity of human lifestyles challenges our ability to identify the genetic and epigenetic drivers of this age acceleration. Here, we examine how the transition of wild King penguins to zoo husbandry can closely mimic the shift to a Western lifestyle in humans, and shed light on evolutionarily conserved epigenetic changes in responses to sedentary conditions. We show that, just like modern humans, zoo-housed King penguins experience an extended lifespan, but this comes at the cost of accelerated epigenetic ageing throughout life. This accelerated ageing is associated with differential methylation in key growth and maintenance pathways including the mTOR and PI3K/Akt networks, as well as in specific pathways of lipid-rich diet adaptation and heart-function. Our results demonstrate the deeply conserved link between sedentary behaviour and food availability on the one hand, and age acceleration on the other. Such evolutionary evidence may in turn help us to improve risk detection and, ultimately, therapeutics for lifestyle-induced age acceleration in humans7.

genomics↗

bioRxiv2024

Human reproduction comes at the expense of faster aging and a shorter life

Evolutionary theories suggest a trade-off between resources allocated to reproduction and those allocated to self-maintenance, and predict that higher reproductive output entails a shorter lifespan. This study investigates the impact of childbearing on aging and lifespan using data from contemporary Finnish twin women. We model the association between reproductive trajectories and survival in 17,080 women, and assess biological aging in a subset of participants (N=1,117) using the PCGrimAge clock, an algorithm trained to predict biological aging and mortality risk from DNA methylation. Our findings suggest that early childbearing, numerous pregnancies or nulliparity all contribute to accelerated aging and increased mortality risk. These results provide strong evidence for the existence of a trade-off between reproduction, aging and lifespan in modern humans, and provide novel insights into the genetic and lifestyle determinants of healthspan.

evolutionary biology↗

bioRxiv2023

Proteostatic tuning underpins the evolution of novel multicellular traits

The evolution of multicellularity paved the way for the origin of complex life on Earth, but little is known about the mechanistic basis of early multicellular evolution. Here, we examine the molecular basis of multicellular adaptation in the Multicellularity Long Term Evolution Experiment (MuLTEE). We demonstrate that cellular elongation, a key adaptation underpinning increased biophysical toughness and organismal size, is convergently driven by downregulation of the chaperone Hsp90. Mechanistically, Hsp90-mediated morphogenesis operates by destabilizing the cyclin-dependent kinase Cdc28, resulting in delayed mitosis and prolonged polarized growth. Reinstatement of Hsp90 or Cdc28 expression resulted in shortened cells that formed smaller groups with reduced multicellular fitness. Together, our results show how ancient protein folding systems can be tuned to drive rapid evolution at a new level of biological individuality by revealing novel developmental phenotypes. TeaserDownregulation of Hsp90 decouples cell cycle progression and growth to drive the evolution of macroscopic multicellularity.

evolutionary biology↗

bioRxiv2023

Early-life environmental effects on mitochondrial aerobic metabolism: an experimental brood size manipulation in wild great tits

Parental care (including postnatal provisioning) is a major component of the offsprings early-life environment. In avian species, the number of chicks in the nest and subsequent sibling competition for food are known to affect chicks growth, leading in some cases to long-lasting effects for the offspring. Because of its central role in converting energy, variation in the offsprings mitochondrial metabolism could be an important pathway underlying variation in growth patterns. Here, we performed a brood size manipulation in great tits (Parus major) to unravel its impact on offsprings mitochondrial metabolism and reactive oxygen species (ROS) production in red blood cells. We investigated the effects of brood size on chicks growth and survival, and tested for long-lasting effects on juvenile mitochondrial metabolism and phenotype. As expected, chicks raised in reduced broods had a higher body mass compared to enlarged and control groups. However, mitochondrial metabolism and ROS production were not significantly affected by the treatment either at chick or juvenile stages. Chicks in very small broods were smaller in size and had higher mitochondrial metabolic rates. The nest of rearing has a significant effect on nestling mitochondrial metabolism, yet variation in mitochondrial metabolism at the early-life stages are not associated with survival chances. The contribution of the rearing environment in determining offspring mitochondrial metabolism emphasizes the plasticity of mitochondrial metabolism in changing environments. Further studies would be needed to closely investigate what are the major environmental cues affecting the offspring mitochondrial metabolism during the growth period.

physiology↗

bioRxiv2023

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of gene expression: an experimental study in a wild bird species

Offspring phenotype at birth is determined by its genotype and the prenatal environment including exposure to maternal hormones. Variation in both maternal glucocorticoids and thyroid hormones can affect offspring phenotype. However, the underlying molecular mechanisms shaping the offspring phenotype, especially those contributing to long-lasting effects, remain unclear. Epigenetic changes (such as DNA methylation) have been postulated as mediators of long-lasting effects of early-life environment. In this study, we determined the effects of elevated prenatal glucocorticoid and thyroid hormones on handling stress response (breath rate), DNA methylation and gene expression of glucocorticoid receptor (GCR) and thyroid hormone receptor (THR) in great tit (Parus major). Eggs were injected before incubation onset with corticosterone (main avian glucocorticoid) and/or thyroid hormones (thyroxine and triiodothyronine) to simulate variation in maternal hormone deposition. Breath rate during handling and gene expression of GCR and THR were evaluated 14 days after hatching. Methylation status of GCR and THR genes were analyzed from the longitudinal blood samples taken 7 and 14 days after hatching, as well as in the following autumn. Elevated prenatal corticosterone level significantly increased the breath rate during handling, indicating enhanced stress response and/or metabolism. Prenatal corticosterone manipulation had CpG-site-specific effects on DNA methylation at the GCR putative promoter region, while it did not significantly affect GCR gene expression. GCR expression was negatively associated with earlier hatching date and chick size. THR methylation or expression did not exhibit any significant relationship with the hormonal treatments or the examined covariates, suggesting that TH signaling may be more robust due to its crucial role in development. This study supports the view that maternal corticosterone may influence offspring metabolism and stress response via epigenetic alterations, yet their possible adaptive role in optimizing offspring phenotype to the prevailing conditions, context-dependency, and the underlying molecular interplay needs further research.

evolutionary biology↗

bioRxiv2022

Associations between brood size, gut microbiome diversity and survival in great tit (Parus major) nestlings

BackgroundThe gut microbiome forms at an early stage, yet data on the environmental factors influencing the development of wild avian microbiomes is limited. As the gut microbiome is a vital part of organismal health, it is important to understand how it may connect to host performance. The early studies with wild gut microbiome have shown that the rearing environment may be of importance in gut microbiome formation, yet the results vary across taxa, and the effects of specific environmental factors have not been characterized. Here, wild great tit (Parus major) broods were manipulated to either reduce or enlarge the original brood soon after hatching. We investigated if brood size was associated with nestling bacterial gut microbiome, and whether gut microbiome diversity predicted survival. Fecal samples were collected at mid-nestling stage and sequenced with the 16S rRNA gene amplicon sequencing, and nestling growth and survival were measured. ResultsGut microbiome diversity showed high variation between individuals, but this variation was not significantly explained by brood size or body mass. Additionally, we did not find a significant effect of brood size on body mass or gut microbiome composition. We also demonstrated that early handling had no impact on nestling performance or gut microbiome. Furthermore, we found no significant association between gut microbiome diversity and short-term (survival to fledging) or mid-term (apparent juvenile) survival. ConclusionsWe found no clear association between early-life environment, offspring condition and gut microbiome. This suggests that brood size is not a significantly contributing factor to great tit nestling condition, and that other environmental and genetic factors may be more strongly linked to offspring condition and gut microbiome. Future studies should expand into other early-life environmental factors e.g., diet composition and quality, and parental influences.

ecology↗

bioRxiv2022

Expression of m6A RNA methylation markers in the hypothalamus of Atlantic salmon

Methylation at the N6-position of adenosine, m6A, is the most abundant mRNA modification in eukaryotes. It is a highly conserved universal regulatory mechanism controlling gene expression in a myriad of biological processes. The role of m6A methylation in sexual maturation, however, has remained largely unexplored. While the maturation process is known to be affected by many genetic and environmental factors, the molecular mechanisms causing variation in the timing of maturation are still poorly understood. Hence, investigation of whether a widespread mechanism like m6A methylation could be involved in controlling of the maturation timing is warranted. In Atlantic salmon (Salmo salar), two genes associated with the age at maturity in human, vgll3 and six6, have been shown to play an important role in maturation timing. In this study, we investigated the expression of 16 genes involved in the regulation of m6A RNA methylation in the hypothalamus of Atlantic salmon with different homozygous combinations of late (L) and early (E) alleles for vgll3 and six6 genes. We found differential expression of ythdf2.2 which encodes an m6A modification reader and promotes mRNA degradation. Its expression was higher in six6*LL compared to other genotypes as well as immature males compared to matures. In addition, we found that the expression levels of genes coding for an eraser, alkbh5, and for a reader, ythdf1, were higher in the hypothalamus of females than in males across all the different genotypes studied. Our results indicate a potential role of the m6A methylation process in sexual maturation of Atlantic salmon, and therefore, provide the first evidence for such regulatory mechanism in the hypothalamus of any vertebrate. Investigation of additional vertebrate species is warranted in order to determine the generality of these findings.

molecular biology↗

bioRxiv2021

Altricial bird early-stage embryos express the molecular "machinery" to respond to maternal thyroid hormone cues

Maternal hormones, such as thyroid hormones transferred to embryos and eggs, are key signalling pathways to mediate maternal effects. To be able to respond to maternal cues, embryos must express key molecular machinery of the hormone pathways, such as enzymes and receptors. While altricial birds begin thyroid hormone (TH) production only at/after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited in the egg. However, it is not understood, how and when altricial birds express genes in the TH-pathway. For the first time, we measured the expression of key TH-pathway genes in altricial embryos, using two common altricial ecological model species (pied flycatcher, Ficedula hypoleuca and blue tit Cyanistes caeruleus). Deiodinase DIO1 gene expression could not be reliably confirmed in either species, but deiodinase enzyme DIO2 and DIO3 genes were expressed in both species. Given that DIO2 coverts T4 to biologically active T3, and DIO3 mostly T3 to inactive forms of thyroid hormones, our results suggest that embryos may modulate maternal signals. Thyroid hormone receptor (THRA and THRB) and monocarboxyl membrane transporter gene (SLC15A2) were also expressed, enabling TH-responses. Our results suggest that early altricial embryos may be able to respond and potentially modulate maternal signals conveyed by thyroid hormones.

developmental biology↗