Refuting Creationism - Neanderthals Evolved By Loss of Genetic Information

Life appearance reconstruction of a Neanderthal male at the Natural History Museum of London.

Photo: Allan Henderson under CC BY 2.0.

Fig. 1: Summary of individuals included in the analyses.

a The geographical and chronological range of the Neanderthal clade individuals and modern humans included in the analysis. The symbols correspond to the n of individuals from each site and are colored as follows: blue = Sima de los Huesos; purple = Krapina; green = late Neanderthals; orange = modern humans. Orange ellipses correspond to the approximated geographical range of the extant modern human assemblage. Age estimates of fossil specimens are provided in Table 1. Background satellite image was downloaded from © Mapbox, © OpenStreetMap, © Maxar and rescaled to fit to figure panel size. b–e Three-dimensional models of the left semicircular canal and vestibule of selected individuals for the four groups considered in the present study.

The inner ear of Neanderthals reveals clues about their enigmatic origin

Creationists will confidently tell you that a loss of genetic information is invariably fatal so can play no part in evolution. They believe this because the frauds at the Discovery Institute have misled them into believing that every piece if DNA and therefore every piece of genetic information has a purpose.

And yet researchers have shown that it was a loss of genetic information following a population bottleneck that gave rise to the classic Neanderthals as a distinct species from their pre-Neanderthal ancestors.

This was the conclusion from a study led by Alessandro Urciuoli (Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona) and Mercedes Conde-Valverde (Cátedra de Otoacústica Evolutiva de HM Hospitales y la Universidad de Alcalá), researchers measured the morphological diversity in the structure of the inner ear responsible for our sense of balance: the semicircular canals.

What is known about the evolutionary origins of the Neanderthals? The evolutionary origins of Neanderthals (Homo neanderthalensis) can be traced back to the divergence between the ancestors of Neanderthals and modern humans (Homo sapiens), which likely occurred between 600,000 and 800,000 years ago. Neanderthals are generally considered to have evolved from populations of Homo heidelbergensis or a closely related species in Eurasia. Here's a breakdown of their evolutionary history:

1. Ancestry and Divergence from Modern Humans
   • Genetic and fossil evidence suggests that Neanderthals and modern humans share a common ancestor, often identified as Homo heidelbergensis or Homo antecessor.
   • The split between the lineages leading to Neanderthals and modern humans likely occurred before 600,000 years ago.
   • The Neanderthal lineage remained in Europe and western Asia, while the modern human lineage evolved in Africa.
2. Early Neanderthal Evolution (≈600,000–400,000 years ago)
   • Fossils from Europe, such as those from Sima de los Huesos in Spain (~430,000 years old), exhibit traits that are intermediate between H. heidelbergensis and later Neanderthals.
   • The Denisovans, an enigmatic sister group to Neanderthals, also branched off from this common ancestor.
3. Classic Neanderthals (≈250,000–40,000 years ago)
   • By about 250,000 years ago, Neanderthals had developed their characteristic features, including:
     • A large brain (on average larger than that of modern humans).
     • A robust skeleton adapted for cold climates.
     • Distinctive facial features such as a large nose and pronounced brow ridges.
   • They spread across Eurasia, from western Europe to Siberia and the Middle East.
4. Interbreeding with Other Humans
   • Neanderthals interbred with early modern humans when the two populations encountered each other.
   • Genetic studies show that non-African modern humans carry about 1-2% Neanderthal DNA, indicating interbreeding between Neanderthals and Homo sapiens around 50,000–60,000 years ago.
5. Extinction (~40,000 years ago)
   • Neanderthals disappeared from the fossil record around 40,000 years ago, likely due to a combination of factors:
     • Climate change.
     • Competition with Homo sapiens.
     • Small, isolated populations leading to inbreeding and genetic decline.

Neanderthals were not a dead-end species but contributed to the genetic makeup of modern humans, leaving a lasting evolutionary legacy.

Can you briefly explain how examining the morphology of the semicircular canals in the inner ear can contribute to our understanding of this evolution?

Examining the morphology of the semicircular canals in the inner ear provides valuable insights into the locomotion and ecological adaptations of Neanderthals and their ancestors. The semicircular canals, part of the vestibular system, are crucial for balance and movement coordination, and their shape and size can reflect differences in locomotor behaviour among hominin species.

How It Contributes to Understanding Neanderthal Evolution:

1. Locomotion and Posture:
   • The semicircular canals influence an organism’s ability to balance during movement.
   • Comparisons between Neanderthals and modern humans show that Neanderthals had slightly different canal proportions, possibly reflecting a more rigid, less agile movement style, suited for rough terrain.
2. Adaptation to Environment:
   • Neanderthals evolved in colder, forested, and mountainous regions, where stability and endurance were likely more crucial than rapid directional changes.
   • Differences in canal morphology suggest they may have had a lower agility compared to early modern humans, aligning with their robust, stocky build.
3. Phylogenetic Relationships:
   • By comparing the semicircular canals of Neanderthals, early Homo sapiens, Homo heidelbergensis, and earlier hominins, researchers can infer how locomotion evolved across different human lineages.
   • Neanderthal canal morphology shows a closer affinity to earlier European hominins (H. heidelbergensis) than to modern humans, supporting the idea of a long, independent evolutionary trajectory.

In short, semicircular canal morphology helps reconstruct how Neanderthals moved and adapted to their environments, shedding light on their evolutionary divergence from modern humans.

The study involved the examination of fossil samples from Atapuerca (Spain) and Krapina (Croatia), as well as from various European and Western Asian sites. The results have been published in Nature Communications and are explained in an Institut Català de Paleontologia news item:

The inner ear of Neanderthals reveals clues about their enigmatic origin

---

New research on the inner ear morphology of Neanderthals and their ancestors challenges the widely accepted theory that Neanderthals originated after an evolutionary event that implied the loss of part of their genetic diversity. The findings, based on fossil samples from Atapuerca (Spain) and Krapina (Croatia), as well as from various European and Western Asian sites have been published in Nature Communications.

---

Neanderthals emerged around 250.000 years ago from European populations—referred to as "pre-Neanderthals"—which inhabited the Eurasian continent between 500.000 and 250.000 years ago. It was long believed that no significant changes occurred throughout the evolution of Neanderthals, yet recent paleogenetic research based on DNA samples extracted from fossils revealed the existence of a drastic genetic diversity loss event between early Neanderthals (or ancient Neanderthals) and later ones (also referred to as "classic" Neanderthals). Technically known as a "bottleneck", this genetic loss is frequently the consequence of a reduction in the number of individuals of a population. Paleogenetic data indicate that the decline in genetic variation took place approximately 110,000 years ago.

The presence of an earlier bottleneck event related to the origin of the Neanderthal lineage was also a widespread assumption among the scientific community. As such, all hypotheses formulated thus far were based on the idea that the earliest Neanderthals exhibited lower genetic diversity than their pre-Neanderthal ancestors, as consequence of a bottleneck event. However, the existence of a bottleneck at the origin of the Neanderthals has not been confirmed yet through paleogenetic data, mainly due to the lack of genetic sequences old enough to record the event and needed for ancient DNA studies.

In a study led by Alessandro Urciuoli (Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona) and Mercedes Conde-Valverde (Cátedra de Otoacústica Evolutiva de HM Hospitales y la Universidad de Alcalá), researchers measured the morphological diversity in the structure of the inner ear responsible for our sense of balance: the semicircular canals. It is widely accepted that results obtained from studying the morphological diversity of the semicircular canals are comparable to those obtained through DNA comparisons.

Image 1. Schematic representation of the changes in morphological diversity along the evolutionary history of the Neanderthal clade. Sima de los Huesos and, particularly, Krapina populations show similarly large amounts of morphological variation, thus suggesting continuity during the Middle Pleistocene. Later, classic Neanderthals instead appear much less diverse, hence hinting for the presence of a drop in phenotypic variation right after the temperature maximum reached around 120.000 years ago, and at the beginning of the Last Glacial cycle.

The study focused on two exceptional collections of fossil humans: one from the Sima de los Huesos site of Atapuerca (Burgos, Spain), dated to 430,000 years old, which constitutes the largest sample of pre-Neanderthals available in the fossil record; and another from the Croatian site of Krapina, this representing the most complete collection of early Neanderthals and dated to approximately 130.000-120.000 years ago. The researchers calculated the amount of morphological diversity (i.e., disparity) of the semicircular canals of both samples, comparing them with each other and with a sample of classic Neanderthals of different ages and geographical origins.

The study's findings reveal that the morphological diversity of the semicircular canals of classic Neanderthals is clearly lower than that of pre-Neanderthals and early Neanderthals, which aligns with previous paleogenetic results. Mercedes Conde-Valverde, co-author of the study, emphasized the importance of the analyzed sample: “By including fossils from a wide geographical and temporal range, we were able to capture a comprehensive picture of Neanderthal evolution. The reduction in diversity observed between the Krapina sample and classic Neanderthals is especially striking and clear, providing strong evidence of a bottleneck event.”

On the other hand, the results challenge the previously accepted idea that the origin of Neanderthals was associated with a significant loss of genetic diversity, prompting the need to propose new explanations for their origin.

We were surprised to find that the pre-Neanderthals from the Sima de los Huesos exhibited a level of morphological diversity similar to that of the early Neanderthals from Krapina. This challenges the common assumption of a bottleneck event at the origin of the Neanderthal lineage

Dr. Alessandro Urciuoli, lead author.
Universitat Autònoma de Barcelona
Barcelona, Spain.

Alessandro Urciuoli is a postdoctoral fellow at the University of Zurich (previously employed at the Universitat Autònoma de Barcelona as a Margarita Salas postdoctoral fellow) and associated researcher at the Institut Català de Paleontologia Miquel Crusafont; Mercedes Conde-Valverde is lecturer at the Universidad de Alcalá and director of the Cátedra de Otoacústica Evolutiva de HM Hospitales and the Universidad de Alcalá.

Publication
Urciuoli, A., Martínez, I., Quam, R., Arsuaga, J. L., Keeling, B. A., Diez-Valero, J. & Conde-Valverde, M. (2025).
Semicircular Canals Shed Light on Bottleneck Events in the Evolution of the Neanderthal Clade.
Nature Communications. https://doi.org/1038/s41467-025-56155-8

Abstract
Revealing the evolutionary processes which resulted in the derived morphologies that characterize the Neanderthal clade has been an important task for paleoanthropologists. One critical method to quantify evolutionary changes in the morphology of hominin populations is through evaluating morphological phenotypic diversity (i.e., disparity) in phylogenetically informative bones as a close proxy to neutral evolutionary processes. The goal of this study is to quantify the degree of disparity in the Neanderthal clade. We hypothesize that a reduction in bony labyrinth disparity is indicative of the underlying genetic variation resulting from bottleneck events. We apply a deformation-based geometric morphometric approach to investigate semicircular canal and vestibule shape of a chronologically broad sample of individuals belonging to the Neanderthal lineage. Our results identify a significant reduction in disparity after the start of Marine Isotope Stage 5 supporting our hypothesis of a late bottleneck, possibly leading to the derived morphology of Late Pleistocene Neanderthals.

Fig. 2: Scenarios of phenetic variation along the evolution of the Neanderthal clade.

a Scenario #1: no occurrence of bottleneck events; b Scenario #2: occurrence of an early bottleneck event between Sima de lo Huesos and Krapina populations; c Scenario #3: occurrence of a late bottleneck event after population of Krapina and before late Neanderthals; d Scenario #4: occurrence of both an early and late bottleneck events. The horizontal line is a schematic representation of time with earlier occurring groups on the left and later occurring ones on the right. The thickness of the horizontal bars corresponds to the suggested phenetic variation. Colors are coded as follows: blue = Sima de los Huesos; purple = Krapina; green = late Neanderthals.

---

Fig. 3: Bivariate scatterplots of a principal component analysis performed on the deformation-fields (raw shape data) obtained from the diffeomorphometric analysis of semicircular canals.

a PC2 vs. PC1; b PC4 vs. PC3. The variance explained by each PC is given within parentheses. 95% confidence ellispes, symbols, and c–f group average shapes (in posterolateral and posteromedial views) are color-coded based on group membership: blue = Sima de los Huesos; purple = Krapina; green = late Neanderthals; orange = modern humans. Source data for this figure can be reproduced using the code and files provided in Supplementary Code 1 and Supplementary Data 3.

---

Fig. 4: Shape and size differences.

Frequency plots of morphological variance (a) and disparity (b) for each group in the semicircular canal shape space. Bootstrapped group distributions (20,000 bootstraps) were computed based on PC1-19 scores (86.7% of variance) to account for the small number of available specimens for fossil groups. The solid lines represent density curves of the frequencies for morphological variance and disparity values between all possible pairs of individuals within each bootstrapped group. The vertical axis represents the frequency of a given disparity or variance value obtained from the bootstrapping of the sample. Vertical dashed lines correspond to group averages for morphological variance and disparity. c Line plot of pair-wise Euclidean distances for the bootstrapped group distribution (20,000 bootstraps). The solid line corresponds to the second and third quartile; dashed lines represent first and fourth quartiles; black dot shows median of the distribution. d Natural logarithm (ln) of the centroid size of semicircular canals for the individuals included in the analysis. Classic Neanderthals display the largest size variation together with modern humans. Color coding as in Figs. 1 and 3. Source data for this figure can be reproduced using the code and files provided in Supplementary Code 1 and Supplementary Data 3.

Urciuoli, A., Martínez, I., Quam, R. et al. Semicircular canals shed light on bottleneck events in the evolution of the Neanderthal clade. Nat Commun 16, 972 (2025). https://doi.org/10.1038/s41467-025-56155-8

Copyright: © 2024 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

Neanderthals are a major headache for creationists for several reasons, and this finding that 'classic' Neanderthals were the result of evolution by loss of genetic information is just one of them.

They also lived several thousands of years before creationism's god created the Universe according to their favourite mythology; and, by contributing their DNA to modern Eurasian Homo sapiens, they refute the childish notion of a single founder couple who did the 'Original Sin' that we all need forgiveness and redemption for, allegedly. Not only was there not a single founder couple; there was not even a single founder species.

No wonder one of their favourite lies is that all we know about Neanderthals is from a single specimen which has been shown to be a modern human with arthritis. In fact, roughly 500 individual Neanderthals have been recovered from over 200 sites in western Eurasia spanning a time range of 400,000 to 40,000 years ago. Certainly enough to show evolutionary change over time, as this paper demonstrates.

Malevolent Designer - How Creationism's Divine Malevolence Ensured Its Zika Virus Infects Developing Babies

Zika virus's non-structural protein NS1 (red) and mitochondria (green) travel through the tunneling nanotube (TNT, gray) from infected to uninfected placental cells.

Image: Mysorekar lab.

A representation of the surface of the Zika virus, with protruding envelope glycoproteins shown in red.

Kuhn and Rossmann research groups, Purdue University

Stealth virus: Zika virus builds tunnels to covertly infect cells of the placenta | BCM

I've written recently about the lengths creationism's divine malevolence must have gone to to ensure one of its nasty little parasitic pathogens, the zika virus, gets to infect as many of its potential victims as possible. Science has now revealed how it then ensures as many babies being carried by its pregnant victims as possible are infected, by sneaking past the maternal/foetal barrier in the placenta.

Zika, is, of course, the mosquito-borne virus that causes microcephaly and associated mental handicap in babies whose mothers were infected during pregnancy.

To ensure the success of this method of increasing the suffering in the world, the designer had a major problem of its own making to overcome - it had given the human foetus a placenta that included a barrier between its circulation and that of the mother. This barrier is normally sufficient to prevent viruses crossing over into the developing foetus, so clearly, if an many children with microcephaly as possible are born, the designer had to find a way to bypass this barrier.

It produced the ingenious method of creating microtubules (small tunnels) between the mother's cells and the foetus's cells in the placenta and simply passing through them!

Unusually for creationism's divine malevolence, which normally behaves like a mindless evolutionary process and reinvents a novel solution for the same problem encountered by a different species, this is the same sneaky method used by a few other viruses to pass from cell to cell in a sheet of tissue, without going outside and making themselves available for the immune system to detect and respond to.

Refuting Creationism - A Simple Mutation Could Have Given Us the Power of Speech.

;

Expression pattern of NOVA1 in the brain of a mouse. NOVA1 in green, nuclei (DAPI) in blue.

Darnell lab.

Model of the evolutionary timing for the 197th amino acid change in the NOVA1 gene, noting the Nova1^hu/hu mice generated in this study. Nova1^hu/hu mice express the modern human-specific amino acid in the NOVA1 protein. The bottom panel shows the corresponding position within the KH2 domain of the NOVA1 protein. Amino acids structurally proximal (<5 Å) to the 197th amino acid, as predicted by AlphaFold2, are highlighted in pink.

Tajima, Y., Vargas, C.D.M., Ito, K. et al (2024) (CC BY 4.0)

The Rockefeller University » A single protein may have helped shape the emergence of spoken language

In the simplistic creationist parody of evolution, intelligently designed to make cult members feel superior to real scientists, the evolution of something like speech in humans must have involved complex, specified, information, that humans alone have that other, lesser, species don't have. Of course, this could only be the result of intelligent design by a supreme intelligence who favours humans, its special creation, who can be whichever your favourite deity is, although it’s not religion because it doesn’t mention God or the Bible. Got it!

The surprising thing is that neither William A. Dembski, nor Michael J. Behe, leading Deception Institute fellows, have written a widely acclaimed (in creationist circles and in selected magazine and newspaper articles emanating from the Deception Institute, for its brilliant conclusive proof of the failure of 'Darwinism') book, detailing the sheer astounding complexity of the genetic basis for human speech, and how this proves we don't share a common ancestor with the African apes.

Perhaps they were aware already of the fact that the genetic basis for human speech involves, no such complexity, but just a single point mutation in a gene we share with the other apes and many other mammals.

Rather than proof of human exceptionalism, our ability to speak turns out to be evidence for common ancestry.

The mutation was discovered by researchers from The Rockefeller University and is a simple substitution of the amino acid isoleucine for valine, in the protein NOVA1 which resulted from the substitution of guanine (G) in the first position in the codon for isoleucine for adenine (A). So, the simplest of all mutations - a single point substitution of one nucleotide for another in a gene, may have enabled humans to speak.

What role does the protein NOVA1 play in human speech? NOVA1 (Neuro-oncological ventral antigen 1) is an RNA-binding protein that plays a significant role in alternative splicing regulation, particularly in the nervous system. It has been implicated in human brain development and cognitive functions, including those related to speech and language.

NOVA1 and Human Speech Evolution

A key study in 2021 by Trujillo et al. demonstrated that NOVA1 was subject to human-specific evolutionary changes. The research focused on a single nucleotide difference between modern humans and Neanderthals/Denisovans in the NOVA1 gene. When this archaic variant of NOVA1 was reintroduced into human brain organoids, it resulted in differences in neuronal connectivity, synaptic organization, and gene expression patterns. These differences suggest that the human-specific version of NOVA1 may have played a role in shaping modern human cognition and speech capabilities.

Potential Mechanisms in Speech

1. Neural Circuit Development: NOVA1 influences the splicing of mRNAs involved in synaptic plasticity and neuronal connectivity. Changes in these pathways could have contributed to the fine-tuning of circuits necessary for complex speech.
2. Motor Control of Speech: Given its role in cortical and motor system development, NOVA1 could be involved in the fine control of motor functions necessary for spoken language.
3. Cognitive and Memory Functions: Language involves working memory and complex cognitive processing, and NOVA1 is known to regulate genes implicated in these functions.

While NOVA1 is not the sole determinant of human speech, its evolution likely contributed to the neural adaptations that support our advanced linguistic capabilities.

Interestingly, the same mutation is not present in Neanderthals or Denisovans who had the same version of NOVA1 as other animals, so must have arisen in Homo sapiens after our evolutionary line diverged from theirs.

The researchers have published their findings, open access, in the journal Nature Communications, and explain it in a science news item from Rockefeller University:

A single protein may have helped shape the emergence of spoken language

---

The origins of human language remain mysterious. Are we the only animals truly capable of complex speech? Are Homo sapiens the only hominids who could give detailed directions to a far-off freshwater source or describe the nuanced purples and reds of a dramatic sunset?

---

Close relatives of ours such as the Neanderthals likely had anatomical features in the throat and ears that could have enabled the speaking and hearing of spoken language, and they share with us a variant of a gene linked to the ability to speak. And yet it is only in modern humans that we find expanded brain regions that are critical for language production and comprehension.

Now researchers from The Rockefeller University have unearthed intriguing genetic evidence: a protein variant found only in humans that may have helped shape the emergence of spoken language.

In a study published in Nature Communications, researchers in the lab of Rockefeller researcher Robert B. Darnell discovered that when they put this exclusively human variant of NOVA1—an RNA-binding protein in the brain known to be crucial to neural development—into mice, it altered their vocalizations as they called to each other.

The study also confirmed that the variant is not found in either Neanderthals or Denisovans, archaic humans that our ancestors interbred with, as is evidenced by their genetic traces that remain in many human genomes today.

This gene is part of a sweeping evolutionary change in early modern humans and hints at potential ancient origins of spoken language. NOVA1 may be a bona fide human ‘language gene,’ though certainly it’s only one of many human-specific genetic changes.

Robert B. Darnell, lead author
The Laboratory of Molecular Neuro-oncology
The Rockefeller University, New York, NY, USA.

Three decades in the making

Anatomical adaptations of the vocal tract and intricate neural networks enable our language capabilities. But the genetics behind them isn’t well understood.

One theorized genetic language driver is FOXP2, which codes for a transcription factor involved in early brain development. People with mutations in this gene exhibit severe speech defects, including the inability to coordinate lip and mouth movements with sound. Humans have two amino acid substitutions in FOXP2 that aren’t found in other primates or mammals—but Neanderthals had them too, suggesting that the variant arose in an ancestor of both human lineages. But some findings on FOXP2 have been disputed, and its role in human language development remains unclear.

Now NOVA1 has arisen as a candidate. The gene produces a neuron-specific RNA binding protein key to brain development and neuromuscular control that was first cloned and characterized by Darnell in 1993. It’s found in virtually identical form across a wide swath of the biosphere, from mammals to birds—but not in humans. Instead, we have our own unique form characterized by a single change of an amino acid, from isoleucine to valine, at position 197 (I197V) in the protein chain.

I197V isn’t the only amino acid substitution that distinguishes modern humans from other organisms, points out first author Yoko Tajima, a postdoctoral associate in Darnell’s lab. Several of them may be integral to brain development.

Such changes may have played important roles in the acquisition of characteristics that have contributed to the emergence, expansion, and survival of Homo sapiens.

DR. Yoko Tajima, first author.
The Laboratory of Molecular Neuro-oncology
The Rockefeller University, New York, NY, USA.

A specialist in how RNA binding proteins modulate gene expression, Darnell has been researching NOVA1 since the early 1990s, when he and his colleagues first identified it as the trigger of a neurologic autoimmune disorder called POMA that can cause extreme motor dysfunction. Recently they have begun to identify cases in which NOVA1 genetic variants are associated with developmental language and motor difficulties.

“Understanding NOVA1 has been a career-long effort for me,” he says.

The current study, led by Tajima, used CRISPR gene editing to replace the common NOVA1 protein found in mice with the human variant I197V. They then used advanced techniques such as cross-linking immunoprecipitation (CLIP) analysis, a method developed by Darnell, to identify the RNA binding sites of NOVA1 in the mouse midbrain.

The big reveal

The first notable discovery was that the human variant had no impact on RNA binding related to neural development or motor control. It operated exactly as the one it had replaced.

So what was it doing? The second significant finding gave them a hint: binding sites that were substantially affected by the human variant were located at genes that coded for RNAs related to vocalization.

Moreover, many of these vocalization-related genes were also found to be binding targets of NOVA1, further suggesting the involvement of NOVA1 in vocalization.

DR. Yoko Tajima.

We thought, wow. We did not expect that. It was one of those really surprising moments in science.

Robert B. Darnell.

Darnell’s lab then joined forces with Rockefeller’s Laboratory of Neurogenetics of Language, headed by Erich D. Jarvis, who studies the molecular and genetic mechanisms underlying vocal learning.

Altered communications

Over the next few years, the collaborators investigated the impact on vocalizations among mice of various ages in different contexts. They found altered vocal patterns among both pups of both sexes and adult males.

All baby mice make ultrasonic squeaks to their moms, and language researchers categorize the varying squeaks as four ‘letters’—S, D, U, and M. We found that when we ‘transliterated’ the squeaks made by mice with the human-specific I197V variant, they were different from those of the wild-type mice. Some of the ‘letters’ had changed.

Robert B. Darnell.

They found similar patterns when they studied the hopeful mating calls of male adult mice exposed to female adult mice in estrus.

They ‘talked’ differently to the female mice. One can imagine how such changes in vocalization could have a profound impact on evolution.

Robert B. Darnell.

The human element

The potential influence of I197V on human evolution became their next focus. To confirm that it wasn’t found in our nearest human relatives—the Neanderthals, who largely lived in Europe, and the Denisovans, named after the central Asian cave where they were discovered—the researchers compared eight human genomes with three high-coverage Neanderthal genomes and one high-coverage Denisovan genome.

As expected, our archaic relatives—from whom we are thought to have split about 250,000-300,000 years ago—had the same NOVA1 protein as all non-human animals.

They then combed through 650,058 modern human genomes in the dbSNP database, a catalog of short sequence variations drawn from people around the world. If an alternative to I197V existed, it would be found here.

Of those 650,058 people, all but six had the human variant. Those six had the archaic variant; because the samples are de-identified, details about them are unknown.

Our data show that an ancestral population of modern humans in Africa evolved the human variant I197V, which then became dominant, perhaps because it conferred advantages related to vocal communication. This population then left Africa and spread across the world.

Robert B. Darnell.

Disease and disorders

In the future, Darnell’s lab will investigate how NOVA1 regulates language function with an eye on language or developmental disorders.

We believe that understanding these issues will provide important insights into how the brain operates during vocal communications—and how its misregulation leads to certain disorders.

DR. Yoko Tajima.

Its neural pathways may come into play, for example, when various disorders renders someone unable to speak. Perhaps it influences the development of nonverbal autism; NOVA1 is one of the many genes linked to autism spectrum disorder. And in 2023, the lab reported on a patient with a NOVA1 haploinsufficiency whose neurological symptoms included a speech delay.

Our discovery could have clinical relevance in many ways, ranging from developmental disorders to neurodegenerative disease.

Robert B. Darnell.

Abstract

NOVA1, a neuronal RNA-binding protein expressed in the central nervous system, is essential for survival in mice and normal development in humans. A single amino acid change (I197V) in NOVA1’s second RNA binding domain is unique to modern humans. To study its physiological effects, we generated mice carrying the human-specific I197V variant (Nova1^hu/hu) and analyzed the molecular and behavioral consequences. While the I197V substitution had minimal impact on NOVA1’s RNA binding capacity, it led to specific effects on alternative splicing, and CLIP revealed multiple binding peaks in mouse brain transcripts involved in vocalization. These molecular findings were associated with behavioral differences in vocalization patterns in Nova1^hu/hu mice as pups and adults. Our findings suggest that this human-specific NOVA1 substitution may have been part of an ancient evolutionary selective sweep in a common ancestral population of Homo sapiens, possibly contributing to the development of spoken language through differential RNA regulation during brain development.

Tajima, Y., Vargas, C.D.M., Ito, K. et al.
A humanized NOVA1 splicing factor alters mouse vocal communications. Nat Commun 16, 1542 (2025). https://doi.org/10.1038/s41467-025-56579-2

Copyright: © 2024 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

A single-point mutation in the NOVA1 gene exemplifies how minor genetic changes can lead to profound evolutionary shifts over time. NOVA1 is a crucial RNA-binding protein involved in alternative splicing, shaping how neurons develop and connect in the brain. In modern humans, a small difference in this gene, absent in Neanderthals and Denisovans, has been shown to alter neuronal connectivity and synaptic organization. These changes would have influenced cognitive abilities, including memory, learning, and motor control—key components necessary for the development of complex speech. Such a minute genetic tweak did not instantly grant Homo sapiens the ability to speak in full sentences, but over generations, it contributed to subtle refinements in brain circuitry that eventually supported the evolution of intricate language. It meant evolving humans were able to respond to evolutionary pressure because each refinement in these ability would have given us a significant advantage.

This stands in stark contrast to the creationist notion that human speech must have emerged fully formed by design or the complex ability must have been created by 'complex specified information' being inserted into the genome. Instead, it underscores the gradual, cumulative nature of evolution—where small, naturally occurring mutations provide incremental advantages that are honed by selection over time. NOVA1’s modification alone was not the cause of speech, but as part of a web of genetic and neural adaptations, it played a role in nudging human cognition toward the linguistic sophistication we now take for granted. The story of NOVA1 is a testament to the power of evolution’s tiny steps — showing that complexity arises not through sudden acts of creation but through the relentless refinement of biological systems over millennia.

Malevolent Designer News - How a Fungus Makes Its Host Destroy Its Own Brain

Beauveria bassiana on unidentified insect.

© Lisa Bennett (CC-BY 4.0)

Fungus ‘hacks’ natural immune system causing neurodegeneration in fruit flies - University of Birmingham

If we are to believe creationists, their god created insects such as fruit flies, Colorado beetles, etc., and then set about devising ways to kill them with, amongst other pathogens, fungi that infect them and destroy them from inside.

One of the problems this supposedly intelligent designer had to overcome was the immune system it had given the insects in order to protect them from the pathogens it was designing to kill them.

According to an open access paper just published in PLOS Biology by a team led by Professor Alicia Hidalgo from School of Biosciences, The University of Birmingham, one species of parasitic fungus, Beauveria bassiana, cleverly turns its host's immune system against its host, making it destroy its own brain. Although this fungus does not affect mammals, so poses no threat to humans, the team warns that it is possible that another fungus could use a similar technique against mammals, including humans.

Creationism in Crisis - Scientists Are Questioning Human Evolution - But Not In The Way Creationists Had Hoped

Ai-Generated Image (ChatGPT4o)

This article is best read on a laptop, desktop, or tablet

A new model upends the decades-old “hard steps” theory that intelligent life was an incredibly improbable event and suggests that maybe it wasn't all that hard or improbable. The team of researchers said the new interpretation of humanity’s origin increases the probability of intelligent life elsewhere in the universe.

Credit: NASA. All Rights Reserved.

Does planetary evolution favor human-like life? Study ups odds we’re not alone | Penn State University

An interdisciplinary team of astrophysicists and geoscientists has questioned the evolution of a human-like intelligent species. But the question is not about whether, as creationists have been predicting for 50 plus years, but just how easy or difficult was it? That we evolved was never in any doubt.

The relevance of the easy/difficult question is that it affects our calculation of the probability of similar intelligent life evolving on other planets. If each step in its evolution was hard (the 'hard step' model), then we may be alone in the Universe; if easy, then the Universe could be teeming with life.

Unintelligent Design - A Bird-Brained Designer?

Birds Have Developed Complex Brains Independently from Mammals - campusa-magazine - UPV/EHU

You might expect an intelligent designer to use the same solution to the same problem. After all, no intelligent watchmaker would keep reinventing the movement he or she puts in watches. In fact, an expert horologist can look inside a good watch and tell you who make it, not because the maker's name is engraved inside the case but because the same watchmaker will have used the same design over and over again, maybe varying the outward appearance of the watch and adding some functions like date and phases of the moon, but the basic movement will be the same.

And this is how you can tell that whatever designed living organisms was not an intelligent designer, because whatever it is, it keeps designing different solutions to the same problems. For instance, having designed the basic vertebrate nervous system to have a brain at one end and a cord running through the spinal column, it would have used the same starting components when it came to giving some of those vertebrates the intelligence to make tools, solve puzzles and plan ahead.

Not so creationism's intelligent designer.

Like an amnesiac it seems to have forgotten whichever solution it designed first for the three vertebrate orders in which intelligence is to be found - birds, reptiles and mammals. Starting with the ancestral reptilian brain, the design process has produced two different ways of producing the pallium (the part of the brain responsible for cognition, learning and memory recall) in birds and mammals.

Refuting Creationism - A Mass Extinction of Plants Due To Climate Change - 5,000 Years Before 'Creation Week'

Flora and fauna in Siberia at the last glacial maximum

AI-generated image (ChatGPT4o)

Image of Lake Ilirney during field work in Chukotka, Russia

Photo: Alfred Wegener Institute / Luise Schulte.

Single view - AWI

10,000 years or so before creationism's little god created the small flat planet with a dome over it, thinking it was a universe, as described in the creation myth in the Bible, there was a mass extinction due to global climate change. In addition to the loss of the Ice Age megafauna, such as the woolly mammoth, woolly rhinoceros, cave lions, etc. over most of Eurasia and North America when temperatures rose at the end of the last glaciation, we also lost a lot of the Ice Age-adapted plants.

But, because plants tend not to fossilise so readily as the bones of large mammals, we didn't know until now, just how extensive this loss was, and more importantly, what a similar rise in temperatures is going to mean for the extant flora.

To redress this gap, a team of researchers from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI), Germany, have analysed DNA recovered from plant remains in the sediment of lakes in Siberia and Alaska. In doing so, they have discovered how the temperature affects the way plants interact, tending to support one another in cold weather and competing with one another in warm weather. A rise in ambient temperature meant increasing competition and loss of mutual support.

Refuting Creationism - Where Europeans' Ancestors Came From - Thousands of Years Before 'Creation Week'

Reconstruction of Yamnayan life in the Pontic Area, 5000 years ago

AI-generated image (ChatGPT4o)

Reconstruction of Yamnayan life in the Pontic Area, 5000 years ago.

AI-generated image (ChatGPT4o).

New research based on an analysis of the genomes of 435 individuals has revealed the rich history of the ancestors of modern Europeans, especially the mixing of multiple ethnic groups in the Pontic Area - modern Ukraine - between 8,400 and 4,000 year ago which eventually gave rise to the Yamnaya people who get their name from the Russian for 'pit burial' (Yamna in Ukrainian).

Before the Yamnaya spread into Europe, they were preceded by two earlier waves of migration: firstly, hunter-gatherers who arrived about 45,000 years ago having interbred with and replaced the Neanderthals who had lived there for the previous 250,000 years. These were followed by farmers who came from the Middle East, starting about 9,000 years ago.

The Yamnaya, having formed a stable linguistic and cultural group, and either invented or copied ox-drawn carts and skilled horsemanship, which gave them great mobility, began to expand their range, probably under population pressure beginning about 5,300 years ago and lasting for some 1,800 years, eventually reaching all parts of Western Europe including the Iberian Peninsula and the British Isles.

Malevolent Designer News - How Cancer is Cleverly Designed to Trick Our Immune System

Mitochondrial transfer and metabolic reprogramming of the tumor microenvironment aid cancer immune evasion

Mitochondrial transfer and metabolic reprogramming of the tumor microenvironment aid cancer immune evasion.

How Cancer Cells Trick the Immune System by Altering Mitochondria - Okayama University

There is an ongoing arms race between medical science and cancer - and guess whose side creationism's intelligent designer appears to be on.

Yep, it's the same intelligent designer who designed cancers in the first place by creating an error-prone DNA replication mechanism that goes wrong, as does the error-correction mechanism it designed to try to rectify its faulty design with an added layer of complexity. And one of the results of it going wrong is cancer.

One of the more hopeful treatments for cancer was a tailor-made immunotherapy in which specific antibodies to the cancer cells were used to attack the cancer and treat it like a parasitic pathogen, by training the immune system to recognise the cancer and attack and destroy it.

But, true to form, creationism's divine malevolence has hit back by designing a response by cancer cells to attack by cells of the immune system.

We can be sure this is the work of creationism's intelligent designer because William A Dembski, the Discovery Institute's flunky and pseudoscientist in residence, tells us that any genetic sequence that produces a function must have been given 'specified information' in the form of the DNA that codes for that specific protein because, so he claims, specified information is too complex to have evolved.

Refuting Creationism - Human Cannibalism In Europe - 8,000 Before Creation Week

The entrance to the Maszycka Cave in southern Poland

Photo: Darek Bobak

This article is best read on a laptop, desktop, or tablet

The 18,000-year-old discoveries from the Maszycka Cave include decorated hunting tools made of bone and antler.

Photo: Darek Bobak.

Information for the Media - Georg-August-Universität Göttingen

A good 8,000 years before creationism's little god created the small flat planet with a dome over it as described in Genesis, modern humans were painting wonderful paintings in caves in France and Spain, and cannibalising other humans in what is now southern Poland.

These people were the Magdalenian, a pan-European culture that existed during the Last Glacial Maximum, who are widely regarded as having a form of religion and belief in an afterlife, or at least a spiritual connection to the animals they hunted and depicted on cave walls. However, judging by their cannibalism and casual disposal of human remains along with the bones of the species they hunted for food, and the fact that they decorated and used human bones as utilities such a drinking cups made from human skull caps, they may not have had much regard for the dead.

Creationism Refuted - The Real Universe Shows Us The Bible's Authors Just Make Stuff Up -

Euclid image of a bright Einstein ring around galaxy NGC 6505

Close-up of the Einstein ring around galaxy NGC 6505

ESA - Euclid discovers a stunning Einstein ring

No matter how much you insist that words meant something different in those days, or the description is a poetic allegory or a metaphor the meaning of which is beyond us, the early verses of the Bible clearly and unambiguously describe a universe consisting of a small flat planet with a dome over it with the sun, moon and stars stuck to the underside of the dome.

This, of course, is a childlike description of what the authors saw as they looked up into the sky and saw what looked like a dome, and Earth was more or less flat, give or take a few low hills, so that is what, in their child-like naivety, they described:

How the Bible's authors saw the Universe.

And God said, Let there be a firmament in the midst of the waters, and let it divide the waters from the waters. And God made the firmament, and divided the waters which were under the firmament from the waters which were above the firmament: and it was so. And God called the firmament Heaven. And the evening and the morning were the second day. And God said, Let the waters under the heaven be gathered together unto one place, and let the dry land appear: and it was so. And God called the dry land Earth; and the gathering together of the waters called he Seas: and God saw that it was good.

Genesis 1.6-10

---

And God said, Let there be lights in the firmament of the heaven to divide the day from the night; and let them be for signs, and for seasons, and for days, and years: And let them be for lights in the firmament of the heaven to give light upon the earth: and it was so. And God made two great lights; the greater light to rule the day, and the lesser light to rule the night: he made the stars also. And God set them in the firmament of the heaven to give light upon the earth, And to rule over the day and over the night, and to divide the light from the darkness: and God saw that it was good.

Genesis 1.14-18

Now, as we learn more about the Universe as we develop increasingly sophisticated scientific instruments for examining it, we discover just how childishly naïve the Bible's authors were and so show to anyone interested in truth that the Bible could not possibly have been written or inspired by the creator god described in it, unless that god wanted to mislead us so that it would take humanity another three thousand years or more to discover its lies - and what would have been the point of that?

Mind you, the same creator god could have told us about germs, atoms or electricity or how to make a steam engine or a motor car, but either chose not to or didn't know about those things, because the people who invented it didn't know about those things either. What 'science' there is in the Bible is no better than the primitive understanding of Bronze Age pastoralists.

Abiogenesis News - Closing Another of Creationism's God-Shaped Gaps - Still No God Found

Formation of polyester protocells under early Earth-like conditions Polyester microdroplets, possible precursors to life, were formed from alpha-hydroxy acids (αHAs) in early Earth-like conditions even at low reaction volume, low reactant concentrations, and/or high NaCl or KCl concentrations.

Credit: Associate Professor Tony Z. Jia

How life’s building blocks took shape on early Earth: the limits of membraneless polyester protocell formation – ELSI｜EARTH-LIFE SCIENCE INSTITUTE

Creationism’ ever-shrinking little god that sits in the abiogenesis gap, just got smaller with the news that researchers led by PhD student Mahendran Sithamparam of the Space Science Center (ANGKASA), Institute of Climate Change, National University of Malaysia, working at the Earth-Life Science Institute (ELSI) in the Institute of Science, Tokyo, Japan, have shown how primitive protocells could have formed under a wide range of realistic probiotic Earth conditions. The research team included scientists from Taiwan and China.

The research showed that membraneless protocells could have formed by polymerization of alpha-hydroxy acids (αHAs) to form polyester microdroplets, not to be confused with the modern plastic polyester. These polymers were polymers of esters - simple organic compounds which are chemically similar to the monomers that make modern polyester fibres.

Tell me all about micro polyester droplets as possible early protocells. Micro polyester droplets have recently been investigated as potential early protocells due to their ability to form spontaneously in prebiotic conditions and exhibit behaviours that mimic some cellular properties. Here’s a detailed breakdown:

1. What Are Micro Polyester Droplets?
   Micro polyester droplets are tiny, membraneless liquid-like structures composed of polyester molecules. Polyesters are a class of polymers that can form via simple condensation reactions between hydroxy acids or polyhydroxy-polycarboxylic acids, which could have been abundant on early Earth.
2. Why Are They of Interest in Protocell Research?
   The origin of life research has long been interested in how early protocells might have formed before the advent of phospholipid membranes. Traditional models include fatty acid vesicles, but recent studies suggest that polymer-based droplets, such as micro polyester droplets, could have played a role. They are particularly interesting because:
   • They **form spontaneously** under plausible prebiotic conditions.
   • They can **sequester biomolecules** like RNA and proteins, potentially aiding primitive metabolism.
   • They exhibit **phase separation**, which allows concentration and compartmentalization of biochemical reactions, a key prerequisite for cellular life.
3. Formation Under Prebiotic Conditions
   Researchers have demonstrated that polyester droplets can form in environments mimicking early Earth. This could occur in:
   • Hydrothermal vents where temperature fluctuations drive condensation reactions.
   • Shallow pools with cycles of wet-dry conditions, which promote polymerization.
   • Areas rich in hydroxy acids, which could be produced abiotically via atmospheric or hydrothermal chemistry.
4. Chemical Properties and Stability
   
   • Polyester droplets are more **chemically robust** than lipid vesicles, which are sensitive to changes in pH and salinity.
   • They are **highly dynamic**, meaning they can fuse, divide, and change size—behaviours reminiscent of primitive cell-like compartments.
   • They can **absorb and concentrate organic molecules**, including amino acids and nucleotides, which could facilitate early biochemical evolution.
5. Relevance to the RNA World Hypothesis
   A major challenge for the RNA world hypothesis is how RNA molecules could have been concentrated and protected from degradation. Micro polyester droplets provide a potential solution:
   • They can **selectively encapsulate RNA**, providing a stable environment for early replication.
   • They offer **compartmentalization**, a crucial step toward molecular evolution and the emergence of self-sustaining reactions.
   • Some studies suggest they could support **primitive metabolic cycles** by allowing localized chemical reactions.
6. Comparison to Other Protocell Models
   
   Feature
   1. Stability
      • Polyester Droplets: High
      • Fatty Acid Vesicles: Moderate
      • Coacervates: High
   2. Formation Ease
      • Polyester Droplets: Simple polymerization
      • Fatty Acid Vesicles: Requires amphiphiles
      • Coacervates: Require charges polymers
   3. RNA Compatibility
      • Polyester Droplets: High
      • Fatty Acids Vesicles: Moderate
      • Coacervates: High
   4. Dynamic Behaviour
      • Polyester Droplets: Yes
      • Fatty Acid Vesicles: Limited
      • Coacervates: Yes
   5. Enclosure of Molecules
      • Polyester Droplets: Strong
      • Fatty Acid Vesicles: Weak
      • Coacervates: Strong
7. Possible Pathways to True Cellular Life
   If micro polyester droplets played a role in early life, they could have eventually given way to more complex protocells by:
   1. Incorporating **primitive catalysts**, such as metal ions or ribozymes, to drive chemical reactions.
   2. Developing **membrane-like structures**, either by merging with lipids or evolving into amphiphilic polymers.
   3. Enabling **genetic material replication**, forming a link between compartmentalization and genetic evolution.
8. Challenges and Open Questions
   
   • How did these droplets transition into more complex cellular structures?
   • Could they catalyse reactions autonomously, or would additional molecules be needed?
   • Were polyester-based protocells widespread, or just one of many competing prebiotic compartments?

Conclusion
Micro polyester droplets present an exciting alternative or complement to traditional lipid-based protocell models. Their ability to encapsulate biomolecules, self-organize, and remain stable under a range of conditions makes them a strong candidate for early protocellular life. Further research into their chemical properties and evolutionary potential could provide deeper insights into life’s origins.

The research findings are published in the American Chemical Society journal ACS Bio & Med Chem Au and are explained in a news release from the Earth Life Science Institute, Tokyo:

How life’s building blocks took shape on early Earth: the limits of membraneless polyester protocell formation

---

New research reveals polyester microdroplets, proposed as model membraneless protocells, formed under a wide range of prebiotic conditions, suggesting these molecules were more widespread than previously thought.

---

One leading theory on the origins of life on Earth proposes that simple chemical molecules gradually became more complex, ultimately forming protocells—primitive, non-living structures that were precursors of modern cells. A promising candidate for protocells is polyester microdroplets, which form through the simple polymerisation of alpha-hydroxy acids (αHAs), compounds believed to have accumulated on early Earth possibly formed by lightning strikes or delivered via meteorites, into protocells, followed by simple rehydration in aqueous medium. A recent study from the Earth-Life Science Institute (ELSI) at Institute of Science Tokyo provides new evidence supporting the formation of polyester microdroplets under a wider range of realistic prebiotic conditions than previously thought.

Led by PhD student Mahendran Sithamparam of the Space Science Center (ANGKASA), Institute of Climate Change, National University of Malaysia as the first author and co-supervised by ELSI’s Specially Appointed Associate Professor Tony Z. Jia and ANGKASA Research Scientist Kuhan Chandru, the study explored the formation of these microdroplets under conditions more reflective of early Earth. The team found that polyester microdroplets could form even in salt-rich environments, at low αHA concentrations, and in small reaction volumes. This expands on previous research, which primarily considered their formation at high concentrations or in larger bodies of water such as coastal areas of lakes or hot springs. The findings suggest instead that polyester protocells were likely more widespread than previously thought, potentially forming in confined spaces like rock pores or even in high-salt environments such as briny pools or oceanic environments.

In 2019, the research team discovered that polyester microdroplets could form through a simple dehydration process. When gently heated to 80°C, phenyllactic acid (PA), a type of αHA, transitioned into a gel-like substance that subsequently formed membraneless droplets when rehydrated. In their latest study, the researchers investigated whether these microdroplets could form under more dilute or lower volume conditions, similar to those expected on prebiotic Earth.

Earlier laboratory tests often used high initial concentrations and volumes of αHAs in the hundreds-of-millimolar or microliter range, respectively, which may not reflect the conditions on prebiotic Earth, where such conditions were unlikely; this is why we needed to push the limits of the polymerisation droplet assembly processes to see whether assembly of such protocells would have actually been viable on early Earth.

Associate Professor Tony Z. Jia, co-corresponding author
Earth-Life Science Institute
Institute of Future Science
Institute of Science Tokyo, Japan.

To simulate these more realistic conditions, the researchers reduced the concentration and volume of PA in synthesis and subsequent droplet formation studies. They found that polyesters could be synthesised and droplets could form with as little as 500 µL of 1 mM PA or 5 µL of 500 mM PA. This suggests that polyester microdroplets could have naturally emerged both in confined spaces, such as rock pores, or dilute environments, such as those following flooding or precipitation.

To further test real-world conditions, the team simulated reactions in salinities resembling those in the ancient ocean. They introduced 1M NaCl, KCl, and MgCl2 to the PA reactants, finding that polyester synthesis and microdroplet assembly could proceed in NaCl and KCl but not in MgCl2. This suggests that polyester microdroplets would have been more likely to form in water bodies with specific salt compositions, such as those high in NaCl and KCl but low in MgCl2, favourable to αHA polymerisation and subsequent polyester microdroplet assembly.

The conclusions of this study clearly show that polyester protocells were likely more common on early Earth than previously thought and also informs the next generation of laboratory studies of the system. Thus, a wide range of primitive environments—including oceanic, freshwater, briny, and confined spaces like rock pores—could have ultimately supported the formation of these protocells both on Earth or elsewhere.

Kuhan Chandru, Co-corresponding author
Space Science Center (ANGKASA)
Institute of Climate Change
National University of Malaysia, Selangor, Malaysia.

This research was made possible through the ELSI Visitor Program, which fosters international collaboration involving ELSI researchers; this program supported Sithamparam on two separate visits to ELSI in 2023, as well as a visit during summer 2023 to ELSI for graduate student Ming-Jing He (National Central University) to complete experiments for her master’s thesis. All experiments were conducted at ELSI, and the findings are featured in the ACS Bio & Med Chem Au Special Issue, 2024 Rising Stars in Biological, Medicinal, and Pharmaceutical Chemistry, of which Jia is an awardee.

Reference

Mahendran Sithamparam¹, Rehana Afrin², Navaniswaran Tharumen¹, Ming-Jing He³, Chen Chen⁴, Ruiqin Yi⁵, Po-Hsiang Wang^3,6, Tony Z. Jia^2,7*, and Kuhan Chandru^1,8,9*
Probing the Limits of Reactant Concentration and Volume in Primitive Polyphenyllactate Synthesis and Microdroplet Assembly Processes ACS Bio & Med Chem Au DOI: 10.1021/acsbiomedchemau.4c00082

1. Space Science Center (ANGKASA), Institute of Climate Change, National University of Malaysia, Selangor 43650, Malaysia
2. Earth-Life Science Institute, Institute of Future Science, Institute of Science Tokyo, 2-12-1-IE-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
3. Department of Chemical Engineering and Materials Engineering, National Central University, No. 300, Zhongda Rd., Zhongli District, Taoyuan 32001, Taiwan (R.O.C.)
4. Biofunctional Catalyst Research Team, RIKEN Center for Sustainable Resource Science (CSRS), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
5. State Key Laboratory of Isotope Geochemistry and CAS Center for Excellence in Deep Earth Science, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China
6. Graduate Institute of Environmental Engineering, National Central University, No. 300, Zhongda Road, Zhongli District, Taoyuan City 320, Taiwan
7. Blue Marble Space Institute of Science, 600 first Ave, Floor 1, Seattle, Washington 98104, United States
8. Polymer Research Center (PORCE), Faculty of Science and Technology, National University of Malaysia, Selangor 43600 Malaysia
9. Institute of Physical Chemistry, CENIDE, University of Duisburg-Essen, 45141 Essen, Germany

*Corresponding authors’ email: tzjia@elsi.jp (Tony Z. Jia) and kuhan@ukm.edu.my (Kuhan Chandru)

Abstract

Polyester microdroplets have been investigated as primitive protocell models that can exhibit relevant primitive functions such as biomolecule segregation, coalescence, and salt uptake. Such microdroplets assemble after dehydration synthesis of alpha-hydroxy acid (αHA) monomers, commonly available on early Earth, via heating at mild temperatures, followed by rehydration in aqueous media. αHAs, in particular, are also ubiquitous in biology, participating in a variety of biochemical processes such as metabolism, suggesting the possible strong link between primitive and modern αHA-based processes. Although some primitive αHA polymerization conditions have been probed previously, including monomer chirality and reaction temperature, relevant factors pertaining to early Earth’s local environmental conditions that would likely affect primitive αHA polymerization are yet to be fully investigated. Hence, probing the entire breadth of possible conditions that could promote primitive αHA polymerization is required to understand the plausibility of polyester microdroplet assembly on early Earth at the origin of life. In particular, there are numerous aqueous environments available on early Earth that could have resulted in varying volumes and concentrations of αHA accumulation, which would have affected subsequent αHA polymerization reactions. Similarly, there were likely varying levels of salt in the various aqueous prebiotic solutions, such as in the ocean, lakes, and small pools, that may have affected primitive reactions. Here, we probe the limits of the dehydration synthesis and subsequent membraneless microdroplet (MMD) assembly of phenyllactic acid (PA), a well-studied αHA relevant to both biology and prebiotic chemistry, with respect to reactant concentration and volume and salinity through mass spectrometry- and microscopy-based observations. Our study showed that polymerization and subsequent microdroplet assembly of PA appear robust even at low reactant concentrations, smaller volumes, and higher salinities than those previously tested. This indicates that PA-polyester and its microdroplets are very much viable under a wide variety of conditions, thus more likely participating in prebiotic chemistries at the origins of life.

Sithamparam, Mahendran; Afrin, Rehana; Tharumen, Navaniswaran; He, Ming-Jing; Chen, Chen; Yi, Ruiqin; Wang, Po-Hsiang; Jia, Tony Z.; Chandru, Kuhan
Probing the Limits of Reactant Concentration and Volume in Primitive Polyphenyllactate Synthesis and Microdroplet Assembly Processes ACS Bio & Med Chem Au; doi: 10.1021/acsbiomedchemau.4c00082.

Copyright: © 2025 The authors.
Published by American Chemical Society. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

In addition, the first two paragraphs of the team's introduction to their paper should make grim reading for any creationist still deluded enough to believe the absurd nonsense that biomedical scientists are giving up on the Theory of Evolution and instead turning to magical creationism for answers:

Introduction
Abiogenesis describes the chemical evolution of life on early Earth, i.e., the origins of life (OoL), and involves the formation of simple organic molecules, their polymerization and self-assembly into complex molecules, the emergence of protocells, (1−3) and the development of robust Darwinian evolution before or at the onset of the last universal common ancestor (LUCA). (4) In particular, the synthesis of the primitive chemicals potentially leading to life could have taken place in various settings or by various geological processes on early Earth, including Miller–Urey chemistry, (5) hydrothermal vents, (6,7) shallow pools and lakes, (8,9) panspermia delivery, (10) or wet–dry cycles, (11,12) just to name a few, and likely facilitated possible pathways toward several OoL hypotheses, i.e., the lipid-first world, (13) the metabolism-first world, (14) the RNA world, (15) etc. These primitive environments or processes, combined with energy (i.e., lightning strikes; (16) light, UV-rays, and heat from the young sun; (17) energy from radioactive elements; (18) ionizing radiation; (19) etc.) could have facilitated the formation of many simple biomolecules on early Earth such as amino acids, (20) lipids, (21) nucleotides, (22) simple sugars, (23) or even phosphorus-containing compounds, (24) which could have exhibited important functions or contributions to possibly kick-start the OoL.

However, it is important to recognize that the OoL is not necessarily strictly bound to the canonical biomolecules (i.e., lipids, amino acids, etc.). Other prebiotically available organic molecules could have also played equally essential roles during the emergence of life. (25,26) In particular, we speculate that the properties of α-hydroxy acids (αHAs) lead this category of molecules to be potential key compounds at the OoL due to their active participation of αHAs in chemistries ranging from the prebiotic world all the way to modern biology. For example, citric acid (CA) and malic acid, both αHAs, serve as intermediates in the Krebs cycle. (27−29) Ribosomes, traditionally known for synthesizing proteins, have also been shown to polymerize various αHAs, including lactic acid (LA) and phenyllactic acid (PA), into polyesters, a process that can be directed by mRNA through genetic-code reprogramming. (30) Apart from αHA involvement in biology, αHAs are also essential in biotechnology and biomedicine. (31−38)

Far from being impossible like creationists claim, although they can never explain which laws of chemistry and/or physics makes it so. it seems there are a growing number of ways in which self-replicating systems that evolved into complex cells could have arisen on pre-biotic Earth. Of course, there is no reason to suppose at the pre-DNA stage, that there was only one type of protocell produced by just one set of conditions. There is no reason two or more could not have arisen then either joined forces in symbiosis or one emerged the winner in a competition for resources.

But however it happened, it clearly did not need an unexplained magician suspending the laws of chemistry and physics and making them do thing they couldn't do on their own.

Stand by for the imminent eviction of creationism's little shrinking god from one of its few remaining refuges, as science closes yet another gap where gods used to live in more primitive and unenlightened times.

---

Advertisement

Amazon

Amazon

Amazon

Amazon

Amazon

Amazon

Amazon

Advertisement

Thank you for sharing!

Tweet Link