Human Evolution Research Articles

Skin colour: A window into human phenotypic evolution and environmental adaptation.

As modern humans ventured out of Africa and dispersed around the world, they faced novel environmental challenges that led to geographic adaptations including skin colour. Over the long history of human evolution, skin colour has changed dramatically, showing tremendous diversity across different geographical regions, for example, the majority of individuals from the expansive lands of Africa have darker skin, whereas the majority of people from Eurasia exhibit lighter skin. What adaptations did lighter skin confer upon modern humans as they migrated from Africa to Eurasia? What genetic mechanisms underlie the diversity of skin colour observed in different populations? In recent years, scientists have gradually gained a deeper understanding of the interactions between pigmentation gene and skin colour through population-based genomic studies of different groups around the world, particularly in East Asia and Africa. In this review, we summarize our current understanding of 26 skin colour-related pigmentation genes and 48 SNPs that influence skin colour. Important pigmentation genes across three major populations are described in detail: MFSD12, SLC24A5, PDPK1 and DDB1/CYB561A3/TMEM138 influence skin colour in African populations; OCA2, KITLG, SLC24A2, GNPAT and PAH are key to the evolution of skin pigmentation in East Asian populations; and SLC24A5, SLC45A2, TYR, TYRP1, ASIP, MC1R and IRF4 significantly contribute to the lightening of skin colour in European populations. We summarized recent findings in genomic studies of skin colour in populations that implicate diverse geographic environments, local adaptation among populations, gene flow and multi-gene interactions as factors influencing skin colour diversity.

Generation of 'semi-guided' cortical organoids with complex neural oscillations.

Temporal development of neural electrophysiology follows genetic programming, similar to cellular maturation and organization during development. The emergent properties of this electrophysiological development, namely neural oscillations, can be used to characterize brain development. Recently, we utilized the innate programming encoded in the human genome to generate functionally mature cortical organoids. In brief, stem cells are suspended in culture via continuous shaking and naturally aggregate into embryoid bodies before being exposed to media formulations for neural induction, differentiation and maturation. The specific culture format, media composition and duration of exposure to these media distinguish organoid protocols and determine whether a protocol is guided or unguided toward specific neural fate. The 'semi-guided' protocol presented here has shorter induction and differentiation steps with less-specific patterning molecules than most guided protocols but maintains the use of neurotrophic factors such as brain-derived growth factor and neurotrophin-3, unlike unguided approaches. This approach yields the cell type diversity of unguided approaches while maintaining reproducibility for disease modeling. Importantly, we characterized the electrophysiology of these organoids and found that they recapitulate the maturation of neural oscillations observed in the developing human brain, a feature not shown with other approaches. This protocol represents the potential first steps toward bridging molecular and cellular biology to human cognition, and it has already been used to discover underlying features of human brain development, evolution and neurological conditions. Experienced cell culture technicians can expect the protocol to take 1 month, with extended maturation, electrophysiology recording, and adeno-associated virus transduction procedure options.

Abstract PO1-25-09: A new generation of breast cancer modeling has been achieved through somatic precision gene editing, offering high flexibility and efficiency

Abstract Breast cancer, along with many other cancers, is primarily caused by genetic mutations, typically involving the alteration of nucleotides (A, G, C, T) within genes (with a total of 12 possible mutations). Gene sequencing advancements have facilitated the identification of numerous gene mutations in tumor samples. However, comprehending the precise mechanisms through which these gene mutations contribute to tumor initiation, development, and their impact on tumor characteristics cannot be solely determined from these findings. Therefore, it is crucial to observe the influence of mutations on tumor initiation and development from the moment they occur. Since conducting such observations in human subjects is impractical, animal models with simulated gene mutations have become essential for studying tumor initiation and development. Mice, with a genome comprising approximately 2.7 billion nucleotides, are commonly used as animal models in cancer research due to their cost-effectiveness and high similarity to humans. About 90% of their genes share similar functions, particularly those associated with cancer development. However, achieving precise alterations to specific nucleotides among the 2.7 billion nucleotides within live mouse cells (with a total of 12 possible changes) has presented significant technical challenges. In this study, we present modifications to the CRISPR/Cas9 vector system, enabling homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic mammary epithelial cells, thereby generating mammary tumor models with exceptional flexibility and efficiency. The resulting tumors exhibit significant advantages over traditional mouse models. This technological breakthrough bridges the gap between the potential of CRISPR technology and the accuracy of mouse models, facilitating the study of human tumor evolution and preclinical drug testing. Citation Format: Wen Bu, Yi li. A new generation of breast cancer modeling has been achieved through somatic precision gene editing, offering high flexibility and efficiency [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-25-09.

A Journey into the Evolution of Human Host-Oral Microbiome Relationship through Ancient Dental Calculus: A Scoping Review

One of the most promising areas of research in palaeomicrobiology is the study of the human microbiome. In particular, ancient dental calculus helps to reconstruct a substantial share of oral microbiome composition by mapping together human evolution with its state of health/oral disease. This review aims to trace microbial characteristics in ancient dental calculus to describe the evolution of the human host-oral microbiome relationship in oral health or disease in children and adults. Following the PRISMA-Extension for Scoping Reviews guidelines, the main scientific databases (PubMed, Scopus, Lilacs, Cochrane Library) have been drawn upon. Eligibility criteria were established, and all the data collected on a purpose-oriented collection form were analysed descriptively. From the initial 340 records, only 19 studies were deemed comprehensive enough for the purpose of this review. The knowledge of the composition of ancient oral microbiomes has broadened over the past few years thanks to increasingly well-performing decontamination protocols and additional analytical avenues. Above all, metagenomic sequencing, also implemented by state-of-the-art bioinformatics tools, allows for the determination of the qualitative-quantitative composition of microbial species associated with health status and caries/periodontal disease. Some microbial species, especially periodontal pathogens, do not appear to have changed in history, while others that support caries disease or oral health could be connected to human evolution through lifestyle and environmental contributing factors.

Is Pollution the Primary Driver of Infectious Syndemics?

Syndemics, the adverse interaction of two or more coterminous diseases or other negative health conditions, have probably existed since human settlement, plant and animal domestication, urbanization, and the growth of social inequality beginning about 10–12,000 years ago. These dramatic changes in human social evolution significantly increased opportunities for the spread of zoonotic infectious diseases in denser human communities with increased sanitation challenges. In light of a growing body of research that indicates that anthropogenic air pollution causes numerous threats to health and is taking a far greater toll on human life and wellbeing than had been reported, this paper proposes the possibility that air pollution is now the primary driver of infectious disease syndemics. In support of this assertion, this paper reviews the growth and health impacts of air pollution, the relationship of air pollution to the development and spread of infectious diseases, and reported cases of air pollution-driven infectious disease syndemics, and presents public health recommendations for leveraging the biosocial insight of syndemic theory in responding to infectious disease.

A Concept of Death in Genus Pan: Implications for Human Evolution

An understanding of what death and dying entail is termed a concept of death (CoD), and the human CoD is often viewed as one of the characteristics that distinguishes our species. In this research, I identified an analogous understanding of death and dying in our closest living relatives—genus Pan. Linguistic frameworks designed for studying the CoD in human children look for evidence of understanding of several facets of death. I adapted these frameworks for the non-verbal Pan species, systematically analysing written and video recordings of chimpanzee and bonobo behaviours surrounding death within these new behavioural frameworks. I identified compelling evidence for the comprehension of several aspects of death, and thus for the presence of a human-like CoD in chimpanzees and bonobos. This has implications for our own evolutionary story and raises questions about what makes humans ‘human’.

Between social cognition and material engagement: the cooperative body hypothesis

AbstractIn recent years, social cognition approaches to human evolution and Material Engagement Theory have offered new theoretical resources to advance our understanding of the prehistoric hominin mind. To date, however, these two approaches have developed largely in isolation from one another. I argue that there is a gap between social- and material-centred approaches, and that this is precisely the sociomateriality of the appearance of ancestral hominin bodies, which evolved under selective pressure to develop increasingly complex, cooperative sociality. To get this sociomaterial body in focus, I develop an esthesiological framework, appropriated from Merleau-Ponty (2003), for interpreting the expressive body in an evolutionary and comparative context. The guiding hypothesis of esthesiology is that before being rationality (social or material), “humanity is another corporeity” (Merleau-Ponty, 2003, p. 208). Esthesiology studies the appearance of the body and its sense organs as an intertwining locus of a sensing power (the ability to see, to touch, etc.) and a sensible character (the visible, touchable body). It is this dual-aspect character of the body that facilitates the most basic affective and sensorimotor modes of sociality. Examining these features from a comparative perspective, we find that the human body is distinctively suited to prosocial communication and cooperation: a more cooperative eye, an exposed and communicative skin. I thus propose a cooperative body hypothesis, by analogy with the cooperative eye hypothesis (Tomasello et al., 2007). Esthesiology provides a framework for integrating and interpreting a wide range of otherwise disconnected facts concerning human and nonhuman animal bodies, forms of life, cognition, and evolution, thereby bridging the gap between social cognition and material engagement perspectives. In doing so, however, it not only solves problems and proposes new directions of investigation, but also demands theoretical revisions from each.

The habitat utilization and environmental resilience of Homo heidelbergensis in Europe

The European populations of Homo heidelbergensis may have contributed to the genetic heritage of modern Eurasians. A better understanding of the possible effects of palaeoenvironmental alterations on the evolution of ancient humans can help to understand the origin of developed traits. For this purpose, the spatiotemporal alterations of physical factors were modelled in Europe for the period of 670–190 ka, covering the existence of Homo heidelbergensis in Europe. The factors included the following: paleoclimatic conditions, climatic suitability values of ancient humans, two prey species, and the European beech. Furthermore, the distribution and features of wood used for toolmaking were also investigated. Finally, changes in the relative mortality risk, the percentage of the body covered by clothing, and daily energy expenditure values in the coldest quarter of the year were modelled. The results suggest that H. heidelbergensis inhabited dominantly temperate regions in Europe where prey such as red deer were present. In the northern regions, European beech trees were abundant. When making wood tools, they preferred relatively light but not the strongest woods, which were readily available in the vicinity of the sites. Although hard and heavy woods were also occasionally used, at a European level, significant changes were observed in the relative mortality risk, the percentage of the body covered by clothing, and daily energy expenditure values during the period of 670–190 ka. However, substantial differences between archaeological sites in these values, indicating somewhat ecological variations, were not found during the studied period.

A theory that never was: Wrong way to the “Dawn of speech”

Recent literature argues that a purportedly long-standing theory—so-called “laryngeal descent theory”—in speech evolution has been refuted (Boë et al., 2019, https://doi.org/10.1126/sciadv.aaw3916). However, an investigation into the relevant source material reveals that the theory described has never been a prominent line of thinking in speech-centric sciences. The confusion arises from a fundamental misunderstanding: the argument that the descent of the larynx and the accompanying changes in the hominin vocal tract expanded the range of possible speech sounds for human ancestors (a theory that enjoys wide interdisciplinary support) is mistakenly interpreted as a belief that all speech was impossible without such changes—a notion that was never widely endorsed in relevant literature. This work aims not to stir controversy but to highlight important historical context in the study of speech evolution.

Ethical Dilemmas of Using Artificial Intelligence in Medicine.

Artificial intelligence (AI) is considered the fourth industrial revolution that will change the evolution of humanity technically and relationally. Although the term has been around since 1956, it has only recently become apparent that AI can revolutionize technologies and has many applications in the medical field. The ethical dilemmas posed by the use of AI in medicine revolve around issues related to informed consent, respect for confidentiality, protection of personal data, and last but not least the accuracy of the information it uses. A literature search was conducted through PubMed, MEDLINE, Plus, Scopus, and Web of Science (2015-2022) using combinations of keywords, including: AI, future in medicine, and machine learning plus ethical dilemma. The ethical analysis of the issues raised by AI used in medicine must mainly address nonmaleficence and beneficence, both in correlation with patient safety risks, ability versus inability to detect correct information from inadequate or even incorrect information. The development of AI tools that can support medical practice can increase people's access to medical information, to obtain a second opinion, for example, but it is also a source of concern among health care professionals and especially bioethicists about how confidentiality is maintained and how to maintain cybersecurity. Another major risk may be related to the dehumanization of the medical act, given that, at least for now, empathy and compassion are accessible only to human beings. AI has not yet managed to overcome certain limits, lacking moral subjectivity, empathy, the level of critical thinking is still insufficient, but no matter who will practice preventive or curative medicine in the next period, they will not be able to ignore AI, which under human control can be an important tool in medical practice.

Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development

Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B’s ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.

Endogenous Antimicrobial-Immunomodulatory Molecules: Networking Biomolecules of Innate Immunity.

Endogenous antimicrobial-immunomodulatory molecules (EAIMs) are essential to immune-mediated human health and evolution. Conventionally, antimicrobial peptides (AMPs) have been regarded as the dominant endogenous antimicrobial molecule; however, AMPs are not sufficient to account for the full spectrum of antimicrobial-immunomodulatory duality occurring within the human body. The threat posed by pathogenic microbes is pervasive with the capacity for widespread impact across many organ systems and multiple biochemical pathways; accordingly, the host needs the capacity to react with an equally diverse response. This can be attained by having EAIMs that traverse the full range of molecular size (small to large molecules) and structural diversity (including molecules other than peptides). This review identifies multiple molecules (peptide/protein, lipid, carbohydrate, nucleic acid, small organic molecule, and metallic cation) as EAIMs and discusses the possibility of cooperative, additive effects amongst the various EAIM classes during the host response to a microbial assault. This comprehensive consideration of the full molecular diversity of EAIMs enables the conclusion that EAIMs constitute a previously uncatalogued structurally diverse and collectively underappreciated immuno-active group of integrated molecular responders within the innate immune system's first line of defence.

Revisiting Zeribar lake sediments: Effects ofclimate change on human development in Zagros

Zeribar Lake, located in the west-central Zagros mountains, serves as a key record for understanding the environmental and climate history of West Asia. Studies beginning in the 1960s have examined the lake's sediments to explore how changes in the environment might have influenced major human developments, including the start of the Neolithic period and the formation of early societies. Early research, limited by less precise radiocarbon dating methods, suggested that environmental factors had little impact on the development of cultures. However, with improved dating techniques, a clear link has been established between environmental events and significant stages in human evolution. Analysis of pollen from Zeribar Lake has provided a detailed picture of the region's ecological past. The data shows a significant change from the sparse, cold conditions of the late Pleistocene and early Holocene to the rich oak forests that appeared in the mid-Holocene. This change, previously thought to be caused by more rain, is now understood to be the result of a considerable decrease in temperature, with glaciers once widespread in the area. Updated radiocarbon dating and new interpretations of pollen data suggest that agriculture began earlier than previously thought, around 14,000 years ago, indicating that shifts in the pollen record may reflect the beginnings of farming rather than changes in the climate. These climate changes, initially thought to be minor until 8,000 years ago and believed to involve only slight temperature variations, are now viewed from a different perspective. Despite these revelations, the debate continues among scholars regarding the extent of climate's role in shaping human progress. This article aims to weave together the multifaceted strands of Zeribar Lake's story, bridging paleoecology and archaeology to shed light on the complex dance between humanity and its environment in the Zagros region. It is an endeavor to bolster the bedrock of knowledge for future scholarly pursuits.

A review to the Desert Kite: State of the Art!

Although from the beginning of the historical period, known as the emergence of the writing, it has not passed more than several thousand years, but the history of human evolution can be rooted in an era much older than the one seen: in the age of the hunting-gathering culture! Hunter-gatherer culture was the way of life for early humans until around 11,000 to 12,000 years ago. The lifestyle of huntergatherers was based on hunting animals and foraging for food. Desert kites could be mentioned as a probable transition key from the age of hunting-gathering food to pastoralism, which can be dated today with the development of cosmogenesis and luminescence methods. ‘Desert kites’ are stone constructions made of two long low walls called antennae that converge into an enclosure flanked or not by several small cells. Their shape and archeological evidence suggest that these extensive stone structures may have functioned as game traps, designed to capture and kill large numbers of wild animals. The kite is a landmark that reveals a way of occupying territory. It is an architectural feature of social groups, which hence left a reflection of their territory and catchment. However, these people have sometimes left very few traces enabling their identification. Considering the extent and density of these settlements, the kite is a massive phenomenon whose role was probably crucial in the development of societies in arid regions. It has been seen from the eastern Mediterranean to the eastern Caspian, which suggested finding less of the same structure in the Iranian plateau, as the only suitable linkage, when the northern lands were nearly frozen! Thus, the perspective is reversed from traditional archaeological research, where groups are most often identified by their domestic settlements, with their still undefined modes of subsistence. Kites, as a phenomenon, are therefore a challenge for the archaeology that requires creative and novel approaches.

Darwin, sexual selection, and human evolution

Darwin, sexual selection, and human evolution

Understanding Meaning through Human Evolution

Abstract I argue that meaning is a result of our biological evolution, and that language evolved from primates’ ability to grasp conceptually the most important features of their environment. I hold that natural selection and adaptation ensure that primates both sense and conceptualize their world similarly, and that they therefore think similarly, whenever they receive the same sense impressions. This cognitive similarity enabled our predecessors to learn and develop a language because of the regular association of a particular sound and a particular image. The evolutionary pressure on our predecessors to develop a language was the advantage that such a language had for cooperation and survival. Finally, I argue that the old, but in wider circles frowned-upon theory of meaning, the expressive theory of language, provides the best explanation of the relationship between thought, meaning, and words, because it operates with words and not sentences as the basic semantic unit.

How Chaos Theory Brings Order to the Evolution of Intelligence

This study investigates links between human evolution, information transmission processes, and Chaos Theory, revealing a mathematical pattern underlying evolutionary milestones. By examining the timing of new methods of information transmission, the research confirms a suspected correlation with the Feigenbaum constant δ, a universal factor in Chaos Theory and also found in complex systems. This pattern is prominent in cultural evolution but also extends to biological evolution, as well as to the evolution of written language, suggesting a predictable framework for understanding the progression of complexity in life. The study incorporates findings from various disciplines, including cognitive science, archaeology, and nonlinear dynamics, providing evidence that our development, while it may be random in most aspects, is deterministic in the way complexity grows steadily and evolves information transmission of increasing sophistication. This multidisciplinary approach offers new insights into the links between chaos, complexity, and information, and their role in driving the evolution of intelligent life.

Exploring the intersection of neuroscience and the soul: Understanding the mysteries of the mind

Over the past five decades, scientific progress has underscored the imperative of integrating diverse fields of human inquiry, highlighting their interdependence. Thus, the segregation of humanities from neuroscience appears ludicrous, akin to a jest played upon rational thinkers. With the imminent advent of the human genome project, biotechnology is forging ahead, offering prospects for significant advancements in organ regeneration. While macro evolution may have concluded, micro-evolution persists within the realm of the brain. Neural Darwinism evolves continuously as long as consciousness and memory endure. Amidst diverse internal physiological mechanisms and external stimuli, an alternative theory to preprogrammed directionalism emerges, positing three mechanisms: developmental variation and selection, experiential selections, and reentrant signaling. Reentrant signaling reorients and correlates external inputs, preceding the development of consciousness and psychic evolution. Cholinergic and aminergic neuro-modelling systems emerge as fitting value systems. The primary function of consciousness lies in unifying the myriad categorizations inherent in perception into a cohesive SCENE. Evolution further entails the capacity of reentrant signaling to be guided by a value system, presenting abundant choices. With trillions of neurons and connections, freedom of choice may yield either enlightenment or tyranny. Intriguingly, the evolutionary progression toward worship has shifted from external environments to internal contemplation. Neuroscience stands poised as the next frontier in unraveling the mysteries of the mind and soul, representing the next stage in human understanding and evolution.

Shape variation in modern human upper premolars.

Morphological variation in modern human dentition is still an open field of study. The understanding of dental shape and metrics is relevant for the advancement of human biology and evolution and is thus of interest in the fields of dental anthropology, as well as human anatomy and medicine. Of concern is also the variation of the inner aspects of the crown which can be investigated using the tools and methods of virtual anthropology. In this study, we explored inter- and intra-population morphometric variation of modern humans' upper third and fourth premolars (P3s and P4s, respectively) considering both the inner and outer aspects of the crown, and discrete traits. We worked by means of geometric morphometrics on 3D image data from a geographically balanced sample of human populations from five continents, to analyse the shape of the dentinal crown, and the crown outline in 78 P3s and 76 P4s from 85 individuals. For the study of dental traits, we referred to the Arizona State University Dental Anthropology System integrated with more recent classification systems. The 3D shape variation of upper premolar crowns varied between short and mesio-distally broad, and tall and mesio-distally narrow. The observed shape variation was independent from the geographical origin of the populations, and resulted in extensive overlap. We noted a high pairwise correlation (r1 = 0.83) between upper P3s and P4s. We did not find any significant geographic differences in the analysed non-metric traits. Our outcomes thus suggest that geographical provenance does not play a determinant role in the shaping of the dental crown, whose genesis is under strict genetic control.

Pathogenic variants in human DNA damage repair genes mostly arose in recent human history.

Genome stability is maintained by the DNA damage repair (DDR) system composed of multiple DNA repair pathways of hundreds of genes. Germline pathogenic variation (PV) in DDR genesdamages function of the affected DDR genes, leading to genome instability and high risk of diseases, in particular, cancer. Knowing evolutionary origin of the PVs inhuman DDR genes is essential to understand the etiology of human diseases. However, answer to the issue remains largely elusive. In this study, we analyzed evolutionary origin for the PVs inhuman DDR genes. We identified 169 DDR genes by referring tovarious databases and identified PVs in theDDR genes of modern humans from ClinVar database. We performed a phylogenetic analysis to analyze the conservation of human DDR PVs in 100 vertebrates through cross-species genomic data comparison using the phyloFit program of the PHAST package and visualized the resultsusing theGraphPad Prism software and the ggplot module. We identified DDR PVs from over 5000ancient humansdeveloped a database to host the DDR PVs ( https://genemutation.fhs.um.edu.mo/dbDDR-AncientHumans ). Using the PV data,we performed a molecular archeological analysis tocompare theDDR PVs between modern humans and ancient humans. We analyzed evolution selection of DDR genes across 20 vertebrates using theCodeML in PAML for phylogenetic analysis. Ourphylogenic analysis ruled out cross-species conservation as the origin of human DDR PVs. Ourarcheological approach identified rich DDR PVs shared between modern and ancient humans, which were mostly dated within the last 5000 years. We alsoobserved similar pattern of quantitative PV distribution between modern and ancient humans. We furtherdetected a setof ATM, BRCA2 and CHEK2 PVs shared between human and Neanderthals. Our study reveals that human DDR PVs mostly arose in recent human history. We propose that human high cancer risk caused by DDR PVs can be a by-product of human evolution.