Gene Regulation Is Distinctively Human

Another study finds extreme brain
differences between humans and apes

by Jerry Bergman, PhD

The headline in a University of California announcement reveals a major problem in evolution: “Our brain is arguably the organ that most distinguishes humans from other primates. Its exceptional size, complexity and capabilities far exceed those of any other species on Earth.”[1] The announcement raises the need for an explanation: “How did the brain evolve to exceed that of all other life forms?”  Furthermore, “The remarkable … human brain is … a major foundation for the emergence of distinctive human-specific cognitive and behavioral traits.”[2]

Research by Joshy et al. was designed in order to understand how the human brain could have evolved by researching the differences between humans and the animal considered our closest relative, the chimpanzee. Specifically, they compared six central brain cell types—astrocytes, excitatory neurons, inhibitory neurons, microglia, oligodendrocytes and oligodendrocyte precursor cells. Oligodendrocyte precursor cells are a subtype of the central nervous system’s glial cells.  They have an essential role as precursors to oligodendrocytes and myelin. Other cells are important, but a selection had to be made because of research funds and time limitations.

The three sets of comparisons were between humans and chimpanzees, humans and macaques, and chimpanzees and macaques. Their goal was to support evolutionary ancestry of humans and apes, or at the least to better understand how evolution could have occurred. The term evolution was mentioned in the PNAS paper 92 times.

The motive of the research was to understand “The molecular basis of human brain evolution [because it] is a key piece in understanding the evolution of human-specific cognitive and behavioral traits.”[3] The specific questions the researchers attempted to explore included comparing differentially expressed genes (DEGs) between humans and other primates. They asked,

did human brains experience accelerated regulatory evolution (more DEGs) and did that involve more genes up-regulated than in other species? Does the human brain express more unique genes and highly express unique genes compared to that of chimpanzees? ……To balance the brain cellular heterogeneity and statistical rigor (to account for the limited number of cells), we performed the analysis at the level of six well-defined major cell types, including two classes of neurons and four glial cell types.[4]

The importance of the research and its findings, as explained by the lead researchers, included the following:

Differential gene expression in the human brain compared to nonhuman primate brains is a key molecular feature of human evolution. In this study, we show that differential gene expression of human brains encompasses highly divergent sets of cell-type-specific changes. Despite such cellular diversity, human brain cells have experienced a general increase of gene expression rather than a decrease of gene expression. We reveal specific functional programs that have experienced differential expression in different cell types and genomic and epigenomic features that correlate with such changes. These findings provide a significant conceptual advance to our understanding of human brain evolution.[5]

Background

A common method in conceptualizing the difference between two animal types in order to hypothesize evolution scenarios is to produce genetic comparisons. The number of genetic differences used by the University of University of California – Santa Barbara to compare humans and chimps was “humans share upwards of 95% of our genome with chimpanzees, our closest living relatives.”[6]

Ignoring the problems with this number, the scientists recognized that the problem for evolution is the fact that the human brain’s “exceptional size, complexity and capabilities far exceed those of any other species on Earth.” Evolutionary reasons must exist for the morphological and behavioral chasm between the brains of humans and chimps. The goal of the researchers was to explain by evolution this morphological and behavioral chasm. Although the six cell families identified were similar in humans and chimps, the amount of regulation, they found, was very different. The proper term is up-regulation (increasing the number of products of the genes) and down-regulation (reducing the number of products of the genes).

Although the genetic differences are one important factor in producing the phenotype and behavior differences, the up-down regulation turns out to be a critically important reason for the differences. In addition to the genes, their regulation is critical to constructing a living organism. One method of measuring up-or-down regulation is to measure the amount mRNA (messenger ribonucleic acid) in the cell. The mRNA produced by gene transcription leaves the nucleus to be translated in ribosomes into protein. The more mRNA produced, the more protein that is produced; the less mRNA produced, the fewer proteins  are produced. Survival requires a specific level of protein. Both too much and too little can cause disease and, if not medically or otherwise treated, can result in death.

Evolution of the gene without proper genetic regulation will not generate life. This finding adds one more factor to the list of requirements for vitality beyond genetic information. Joshy’s team confirmed that a major factor explaining the vast difference between humans and chimps, both in body and mind, is genetic regulation. This distance, furthermore, was found between man and rhesus macaques. Their paper concludes,

As we continue to unfold the cellular complexity of the brain, the actual scope of DEGs in the human brain appears to be much broader than previously estimated. Our study supports the acceleration of cell-type-specific functional programs as an important feature of human brain evolution.

Summary

The authors conclude that gene regulatory systems are the main factors resulting in the mental and behavioral chasm between humans and other primates. As they put it, epigenetic variation of gene regulation was “a key molecular feature of human brain evolution.”[7] They also concluded that genetic up/down regulation is exceedingly complex and specific—which creates a huge problem for evolution. Darwinism is a mindless, random process. The author’s conclusion also begs the question of why the human regulatory complex is leaps and bounds ahead of all other primates.

The authors assumed that all other primates are very similar to the two they tested (chimps and rhesus macaques). This raises the question, “Why would only humans be so far ahead of all the other primates?” Humans and chimps or rhesus macaques are believed to have evolved from a common ancestor, yet no evidence of this hypothetical common ancestor exists. Assuming the hypothetical common ancestor of humans was very similar to chimps and rhesus macaques, the question remains why humans would have evolved their finely-tuned, gene-number regulation system but apes and monkeys did not.

References

[1] University of California – Santa Barbara. “Gene expression in the human brain: Cell types become more specialized, not just more numerous,” ScienceDaily, www.sciencedaily.com/releases/2025/01/250102162258.htm, 2 January 2025; emphasis added.

[2] Joshy, D., G. Santpere, and S.V. Yi. “Accelerated cell-type-specific regulatory evolution of the human brain,” Proceedings of the National Academy of Sciences 121(52), DOI: 10.1073/pnas.2411918121, 2024.

[3] Joshy et al., 2024.

[4] Joshy et al., 2024.

[5] Joshy et al., 2024.

[6] Harrison Tasoff, “It’s all about expression,” UC Santa Barbara, January 2, 2025.

[7] Joshy et al., 2024.

Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,900 publications in 14 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,800 college libraries in 27 countries. So far over 80,000 copies of the 60 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.