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PubMed2021

Evolution of DNA methylation in the human brain.

DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.

Animals↗
PubMed2026

Creating bottom-up RNA transfer vehicles from synthetic protein assemblies.

Evolution guides biological systems to populate ecological niches, with viruses among the most successful examples of this principle. Viruses evolved over billions of years to efficiently transfer genetic information. Although viruses are highly diverse, most have converged towards remarkable similarity in the size and shape of their capsids1,2. By contrast, generative models for protein design enable the creation of protein architectures that are absent from nature3-5. Here we investigate whether protein assemblies designed by artificial intelligence can be functionalized to construct nucleic acid transport vehicles that are independent of evolutionary trajectories. By combining natural protein domains with synthetic protein assemblies, we create more than 100 bottom-up RNA transfer vehicles with unique sizes and shapes. These vehicles surpass the RNA transfer efficiency of widely used delivery vehicles by several orders of magnitude. In addition, we demonstrate that their tropism can be programmed by incorporation of computationally designed peptide binders and use them to deliver therapeutically relevant cargo RNAs into a wide range of cellular models. We show the in vivo biodistribution of one of these vehicles in a mouse at near-single-cell resolution, confirm its safety, and use it to perform a gene-editing treatment strategy for Duchenne muscular dystrophy in patient-derived cells and a pig. Our work demonstrates how proteins created by generative artificial intelligence can be harnessed for the rational engineering of RNA transport systems with the desired properties by overcoming the limitations of natural protein diversity.

Journal Article↗
PubMed2026

Chromosomal-level genome assembly of minute pirate bug Orius nagaii Yasunaga, 1993 (Hemiptera: Anthocoridae).

Species of the genus Orius, diminutive predatory insects that act as natural enemies of other arthropods, are frequently employed in agricultural pest management for controlling various pests, such as thrips, mites, aphids, whiteflies, etc. However, the scarcity of high-quality genomic resources for these predators hinders our comprehension of their population evolution and predation ecology. Consequently, we assembled and annotated a chromosomal-scale genome of Orius nagaii by collating PacBio and Illumina sequencing and Hi-C genomic analysis techniques. The final genome assembly size 152.62 Mb, with scaffold and contig N50 lengths of 11.53 and 2.39 Mb, respectively. It is organized into 12 pairs of autosomes and a pair of XY sex chromosomes. The quality assessment of the genomic data with BUSCO revealed a completeness of 98.5% (n = 1,367). Also, 11,917 protein-coding genes were discovered, with 94.28% of them having functional annotations. The high-quality genome of O. nagaii produced serves as a valuable resource for comprehending the interactions between predatory natural enemies and hosts, along with their evolutionary trajectories.

Animals↗
PubMed2004

Genetic correlations, tradeoffs and environmental variation.

Negative genetic correlations among traits are often used as evidence for tradeoffs that can influence evolutionary trajectories in populations. While there may be evidence for negative correlations within a particular environment, genetic correlations can shift when populations encounter different environmental conditions. Here we review the evidence for these shifts by focusing on experiments that have examined genetic correlations in more than one environment. In many studies, there are significant changes in correlations and these can even switch sign across environments. This raises questions about the validity of deducing genetic constraints from studies in one environment and suggests that the interaction between environmental conditions and the expression of genetic covariation is an important avenue for future work.

Animals↗
PubMed2006

Effects of intra-gene fitness interactions on the benefit of sexual recombination.

Whereas spontaneous point mutation operates on nucleotides individually, sexual recombination manipulates the set of nucleotides within an allele as an essentially particulate unit. In principle, these two different scales of variation enable selection to follow fitness gradients in two different spaces: in nucleotide sequence space and allele sequence space respectively. Epistasis for fitness at these two scales, between nucleotides and between genes, may be qualitatively different and may significantly influence the advantage of mutation-based and recombination-based evolutionary trajectories respectively. We examine scenarios where the genetic sequence within a gene strongly influences the fitness effect of a mutation in that gene, whereas epistatic interactions between sites in different genes are weak or absent. We find that, in cases where beneficial alleles of a gene differ from one another at several nucleotide sites, sexual populations can exhibit enormous benefit compared with asexual populations: not only discovering fit genotypes faster than asexual populations, but also discovering high-fitness genotypes that are effectively not evolvable in asexual populations.

Animals↗
PubMed2002

Phylogeographic analysis of a recent radiation of Enallagma damselflies (Odonata: Coenagrionidae).

A phylogenetic hypothesis revealed two recent radiations among species of Enallagma damselflies, and extensive ecological work suggests that both adaptive and nonadaptive processes are involved in these radiations. We analysed the geographical pattern of genetic variability at 868 bp of mitochondrial DNA (mtDNA) among 283 individuals of 5 species displaying little ecological differentiation to identify the ancestral lineage, support their independent evolutionary trajectories and identify historical events and the underlying mechanism for one of these radiations. Nested clade analysis results clearly support a past event of range fragmentation in E. hageni. These Atlantic and Continental hageni races experienced distinct dispersal histories and still maintain nearly nonoverlapping ranges All four other species derive from the Continental hageni. Whereas three species endemic to the Atlantic coastal plain show little genetic variation, E. ebrium shared several haplotypes with the Continental hageni. Contrasting levels of genetic differentiation between E. hageni and E. ebrium in geographical areas associated with distinct events of E. hageni's recent history support the recent origin of this species. Altogether, our results are compatible with a process of radiation via divergence in mate recognition systems within the Continental hageni race following secondary contacts between putative refugial races.

Animals↗
PubMed2003

Molecular evidence for deep phylogenetic divergence in Mandrillus sphinx.

Mandrills (Mandrillus sphinx) are forest primates indigenous to western central Africa. Phylogenetic analysis of 267 base pairs (bp) of the cytochrome b gene from 53 mandrills of known and 17 of unknown provenance revealed two phylogeographical groups, with haplotypes differentiated by 2.6% comprising seven synonymous transitions. The distribution of the haplotypes suggests that the Ogooué River, Gabon, which bisects their range, separates mandrill populations in Cameroon and northern Gabon from those in southern Gabon. The haplotype distribution is also concordant with that of two known mandrill simian immunodeficiency viruses, suggesting that these two mandrill phylogroups have followed different evolutionary trajectories since separation.

Animals↗
PubMed2004

Circum Black Sea phylogeography of Barbus freshwater fishes: divergence in the Pontic glacial refugium.

We used DNA sequence variation at the mitochondrial cytochrome b gene (1141 bp) to assess the phylogeography of Barbus fishes in the Black Sea region. Our aim was to test whether the recent ( approximately 22 000-7500 years ago) freshwater phase of the Black Sea was a conduit for gene flow among freshwater fishes that today are found in streams entering the saltwater Black Sea. Deep phylogeographical breaks suggestive of allopatric divergence were observed between four regional groups of populations. Coalescent simulation used to distinguish between this and an alternative scenario that the phylogeographical structure was due to random lineage sorting showed that the contemporary populations were unlikely (P < 0.001) to have been founded by a single ancestral population. Divergences between the lineages (0.86-2.54%) were dated to the Middle to Late Pleistocene using distances and a molecular clock corrected for superimposed substitutions. Taken together, this evidence suggests that multiple refugial populations survived over several later glaciations in the vicinity of the Black Sea. This Pontic refugium served as the primary source for the postglacial expansion throughout Europe as far as the Atlantic basin. However, only one of the phylogeographical lineages contributed to this dispersion, whereas the others remain restricted to the Black Sea region and followed independent evolutionary trajectories.

Animals↗
PubMed2000

Designing a bridge for consciousness: are criteria for a unification of approaches feasible?

Different intrinsic rules of functioning for body and mind are overemphasized by the mutually exclusive methods of investigation in both consciousness and the sciences. Classical science, alternative and complementary healing, quantum physics, and metaphysics all take drastically different approaches to consciousness research. A bridge is needed to restore the conceptual unity of mind-body. However, the construction of such a bridge paradoxically must rely on consciousness for information. The construction company (Consciousness, Inc.) therefore becomes means and end in the design of the bridge. This piece argues that the methods of each discipline contain research tools and resources to create a bridge that satisfies a unified multidimensional and multidisciplinary conception. The piece further suggests that the framework of the bridge must place consciousness as a partner to physiology in the evolutionary trajectory of life, since problems of survival are a primary consideration in the activity of both. Finally, the piece develops six criteria by which to evaluate the effectiveness of any construction design.

Consciousness↗
PubMed2004

Emergent trade-offs and selection for outbreak frequency in spatial epidemics.

Nonspatial theory on pathogen evolution generally predicts selection for maximal number of secondary infections, constrained only by supposed physiological trade-offs between pathogen infectiousness and virulence. Spread of diseases in human populations can, however, exhibit large scale patterns, underlining the need for spatially explicit approaches to pathogen evolution. Here, we show, in a spatial model where all pathogen traits are allowed to evolve independently, that evolutionary trajectories follow a single relationship between transmission and clearance. This trade-off relation is an emergent system property, as opposed to being a property of pathogen physiology, and maximizes outbreak frequency instead of the number of secondary infections. We conclude that spatial pattern formation in contact networks can act to link infectiousness and clearance during pathogen evolution in the absence of any physiological trade-off. Selection for outbreak frequency offers an explanation for the evolution of pathogens that cause mild but frequent infections.

Biological Evolution↗
PubMed2005

Climatically driven macroevolutionary patterns in the size of marine diatoms over the Cenozoic.

Numerous taxonomic groups exhibit an evolutionary trajectory in cell or body size. The size structure of marine phytoplankton communities strongly affects food web structure and organic carbon export into the ocean interior, yet macroevolutionary patterns in the size structure of phytoplankton communities have not been previously investigated. We constructed a database of the size of the silica frustule of the dominant fossilized marine planktonic diatom species over the Cenozoic. We found that the minimum and maximum sizes of the diatom frustule have expanded in concert with increasing species diversity. In contrast, the mean area of the diatom frustule is highly correlated with oceanic temperature gradients inferred from the delta18O of foraminiferal calcite, consistent with the hypothesis that climatically induced changes in oceanic mixing have altered nutrient availability in the euphotic zone and driven macroevolutionary shifts in the size of marine pelagic diatoms through the Cenozoic.

Animals↗
PubMed2005

The evolution of lethal intergroup violence.

Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

Aggression↗
PubMed2002

Analysis of a library of macaque nuclear mitochondrial sequences confirms macaque origin of divergent sequences from old oral polio vaccine samples.

Nuclear mtDNA sequences (numts) are a widespread family of paralogs evolving as pseudogenes in chromosomal DNA [Zhang, D. E. & Hewitt, G. M. (1996) TREE 11, 247-251 and Bensasson, D., Zhang, D., Hartl, D. L. & Hewitt, G. M. (2001) TREE 16, 314-321]. When trying to identify the species origin of an unknown DNA sample by way of an mtDNA locus, PCR may amplify both mtDNA and numts. Indeed, occasionally numts dominate confounding attempts at species identification [Bensasson, D., Zhang, D. X. & Hewitt, G. M. (2000) Mol. Biol. Evol. 17, 406-415; Wallace, D. C., et al. (1997) Proc. Natl. Acad. Sci. USA 94, 14900-14905]. Rhesus and cynomolgus macaque mtDNA haplotypes were identified in a study of oral polio vaccine samples dating from the late 1950s [Blancou, P., et al. (2001) Nature (London) 410, 1045-1046]. They were accompanied by a number of putative numts. To confirm that these putative numts were of macaque origin, a library of numts corresponding to a small segment of 12S rDNA locus has been made by using DNA from a Chinese rhesus macaque. A broad distribution was found with up to 30% sequence variation. Phylogenetic analysis showed that the evolutionary trajectories of numts and bona fide mtDNA haplotypes do not overlap with the signal exception of the host species; mtDNA fragments are continually crossing over into the germ line. In the case of divergent mtDNA sequences from old oral polio vaccine samples [Blancou, P., et al. (2001) Nature (London) 410, 1045-1046], all were closely related to numts in the Chinese macaque library.

Animals↗
PubMed1999

Environmental variation shapes sexual dimorphism in red deer.

Sexual dimorphism results from dichotomous selection on male and female strategies of growth in relation to reproduction. In polygynous mammals, these strategies reflect sexual selection on males for access to females and competitive selection on females for access to food. Consequently, in such species, males display rapid early growth to large adult size, whereas females invest in condition and early sexual maturity at the expense of size. Hence, the magnitude of adult size dimorphism should be susceptible to divergence of the sexes in response to environmental factors differentially influencing their growth to reproduction. We show that divergent growth of male and female red deer after 32 years of winter warming and 15 years of contemporaneously earlier plant phenology support this prediction. In response to warmer climate during their early development, males grew more rapidly and increased in size, while female size declined. Conversely, females, but not males, responded to earlier plant phenology with increased investment in condition and earlier reproduction. Accordingly, adult size dimorphism increased in relation to warmer climate, whereas it declined in relation to forage quality. Thus, the evolutionary trajectories of growth related to reproduction in the sexes (i) originate from sexual and competitive selection, (ii) produce sexual size dimorphism, and (iii) are molded by environmental variation.

Animal Feed↗
PubMed2025

Molecular features influencing clinical outcome of advanced HER2-positive gastric cancer receiving trastuzumab plus chemotherapy.

BACKGROUND: Less than half of the human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) patients respond to trastuzumab plus chemotherapy, and the outcomes are unsatisfactory. Understanding the underlying mechanisms remains crucial for identifying patients who are more likely to benefit from treatment. PATIENTS AND METHODS: We performed targeted DNA sequencing on paired pre-treatment and progressive tumour tissues from 22 HER2-positive advanced GC patients undergoing first-line treatment with trastuzumab and chemotherapy. Clinicopathological and genomic characteristics were assessed for the correlation with clinical outcomes. RESULTS: A performance status (PS) of 0-1 was associated with improved progression-free survival (PFS) and overall survival (OS) than a PS of 2. Poorly differentiated tumours exhibited shorter PFS than moderate or moderate-poor ones. Pre-treatment amplification of MYC or TOP2A gene was association with increased PFS, and suggested a potential benefit for OS. Patients with higher tumour mutation burden (TMB) experienced significantly worse PFS, while higher chromosome instability (CIN) appeared to be correlated with longer PFS. Compared to non-responders, responders had a higher CIN but similar TMB and intratumoural heterogeneity (ITH). PS and MYC amplification emerged as independent factors related to PFS according to multivariate survival analysis. Additionally, after treatment, TMB significantly increased in non-responders, while CIN significantly decreased in responders. CONCLUSIONS: Pre-treatment MYC amplification and PS were independently associated with clinical outcomes in HER2-positive advanced GC patients treated with first-line trastuzumab plus chemotherapy. Dynamic post-treatment changes in TMB and CIS provide valuable insights into the relationship between therapeutic response and distinct evolutionary trajectories.

Humans↗
PubMed2006

Dermatophytes: recognizing species of clonal fungi.

Now that molecular data have forever changed our perspective on the anthropophilic and zoophilic dermatophyte species, the concepts of these species needs re-evaluation. In this paper, main concepts (morphological, biological (BSC), phylogenetic and genealogical concordance phylogenetic species recognition (GCPSR)) are compared. While in geophilic dermatophytes the application of the BSC works well for species distinction and is supported by molecular data, it is not applicable for the anthropophilic and zoophilic dermatophytes where the majority of species reproduce purely asexually. Also, the application of GCPSR (an operational method to define the limits of species using molecular, multi-locus data) is problematic. GCPSR can be applied in recombining fungi even when recombination is infrequent and fungi lack phenotypic sexuality. In truly clonal fungi, however, no incongruities in multi-locus data are found, and thus separation of species may be difficult. In fungi this problem is currently taken to be non-existent, since clonality is supposed to lead to extinction. In the medically relevant, host-associated dermatophytes, however, is reason to suggest that clonal dermatophyte lineages are able to maintain ongoing populations and to follow independent evolutionary trajectories. We distinguish seasonal, short-lived and long-lived clonal species. The final goal of a species concept, in the dermatophytes as well as in other fungi, is to provide a taxonomic system that reflects the evolution of the fungal species so that the underlying biological trends elucidated in this way may be brought forward to help to guide the clinician in applying optimal therapy and prophylaxis. The application of the different species concepts may have an enormous impact on the nomenclature of dermatophytes, directly affecting the quality of communications with care providers.

Arthrodermataceae↗
PubMed2004

Evolution in a changing environment: a case study with great tit fledging mass.

Heritable phenotypic traits under significant and consistent directional selection often fail to show the expected evolutionary response. A potential explanation for this contradiction is that because environmental conditions change constantly, environmental change can mask an evolutionary response to selection. We combined an "animal model" analysis with 36 years of data from a long-term study of great tits (Parus major) to explore selection on and evolution of a morphological trait: body mass at fledging. We found significant heritability of this trait, but despite consistent positive directional selection on both the phenotypic and the additive genetic component of body mass, the population mean phenotypic value declined rather than increased over time. However, the mean breeding value for body mass at fledging increased over time, presumably in response to selection. We show that the divergence between the response to selection observed at the levels of genotype and phenotype can be explained by a change in environmental conditions over time, that is, related both to increased spring temperature before breeding and elevated population density. Our results support the suggestion that measuring phenotypes may not always give a reliable impression of evolutionary trajectories and that understanding patterns of phenotypic evolution in nature requires an understanding of how the environment has itself changed.

Animals↗
PubMed2006

Ecological specialization and adaptive decay in digital organisms.

The transition from generalist to specialist may entail the loss of unused traits or abilities, resulting in narrow niche breadth. Here we examine the process of specialization in digital organisms--self-replicating computer programs that mutate, adapt, and evolve. Digital organisms obtain energy by performing computations with numbers they input from their environment. We examined the evolutionary trajectory of generalist organisms in an ecologically narrow environment, where only a single computation yielded energy. We determined the extent to which improvements in this one function were associated with losses of other functions, leading to organisms that were highly specialized to perform only one or a few functions. Our results show that as organisms evolved improved performance of the selected function, they often lost the ability to perform other computations, and these losses resulted most often from the accumulation of neutral and deleterious mutations. Beneficial mutations, although relatively rare, were disproportionately likely to cause losses of function, indicating that antagonistic pleiotropy contributed significantly to niche breadth reductions in this system. Occasionally, unused functions were not lost and even increased in performance. Here we find that understanding how the functions were integrated into the genome was crucial to predictions of their maintenance.

Adaptation, Biological↗