Evolution of the Primate Brain: What Makes Us Human?

Darwin’s famous voyage to the Galapagos Islands in 1831 formed the foundation of the theory of evolution [1]. Since then, scientists have applied this theory to investigate the diversity and relationship between species. Although Darwin’s theory of evolution states that humans evolved from primates, the definition of cognitive function and consciousness was not explained clearly.

According to the Cambridge Declaration on Consciousness, “the absence of a neocortex does not appear to preclude an organism from experiencing affective states.” In other words, recent evidence indicates that nonhuman animals have the capability of “generating consciousness” [2].

So, what does make us human? Why are humans so different from nonhuman primates with regards to phenotype, intelligence, and behavior? This article examines how the evolution in a particular region of the primate brain, the neocortex, may account for differences in the cognitive abilities between humans and our closest ancestor, the chimpanzee.

The neocortex is an integral part of the mammalian brain, and was the most recent part of the cerebral cortex to evolve. It can be divided into four lobes—frontal, parietal, occipital, and temporal lobes—which perform a variety of functions ranging from visual acuity to conscious thought [3]. The neocortex is initially thought to have emerged as a simple six-layered structure made up of mature neurons, but it since has evolved into more complex structures [4]. The neocortex ratio—the ratio of the size of the neocortex to the brain volume—has also progressively increased from macaque monkeys to human. Scientists believe that these two disparities in primates’ brains account for the substantial differences in intelligence between humans and nonhuman primates.

While the size of the neocortex is significantly greater in humans than in chimpanzees, there exist several attributes that have retained their similarities throughout primate evolution. A common theme in all primates is the way neurons emerge and position themselves in the neocortex. All neurons began to develop in the embryonic ventricular (VZ) and subventricular (SVZ) zones. The progenitors that appear in these zones develop into the projection neurons that eventually migrate to their respective neocortical layers VI to II in an “inside-out” fashion [5].

Figure 1: A diagram of the differentiation and emergence of the neocortical layers in a mammal

Figure 1: A diagram of the differentiation and emergence of the neocortical layers in a mammal

The enlargement of the cortical surface of the neocortex can be explained primarily by the “radial unit hypothesis,” which states that the neural progenitors symmetrically divide into radial cortical columns. The radial glial cells further divide asymmetrically to produce intermediate progenitor cells, which then divide symmetrically to form neural projection cells. An increase in the number radial glial cells that rise from progenitors is what accounts for the increase in the surface area of the cortical surface without a simultaneous increase in the thickness. During primate evolution, these cortical surfaces expanded into distinct arrangements. A larger size of cortical surface allows for more neural connections, improving cognitive abilities [6, 7].

The use of modern bioinformatics tools, such as RNA sequencing and microarray analysis, provide insights into neocortical development and is particularly significant in elucidating how the modern human brain emerged from primates, especially chimpanzees. The data can then be analyzed.

According to a 1975 paper by King and Wilson, nearly all of the protein-coding sequences in humans and chimpanzees are the same. About 98% of our DNA is shared with that of the chimpanzee. However, these similar genetic sequences cannot and do not account for our drastic phenotypic differences. King and Wilson further clarified that the regulation of gene expression plays a far greater role in accounting for those phenotypic differences. Since changes in gene expression most prominently affect phenotype during the early stages of neocortical development, the importance of examining the embryonic stages of neurogenesis should be emphasized [8].

The “evo-devo” method explores the relationship between the development processes of  organisms and the evolution of those organisms, particularly examining how the development processes fit into the broader context of evolution. The “evo-devo” approach to molecular and development biology involves the analysis of certain regulatory genes, which control the timing, duration, and magnitude of expression levels in chimpanzee and humans, providing more information into the evolution of neurogenesis. One particular example of the pathway of regulatory genes is the successive expression of the Pax6, Tbr2, and Tbr1 genes in the differentiation of neocortical stem cells [9]. Scientists hope that the evo-devo approach will not only identify differentially expressed genes, but also clarify the connection to primate evolution.

Preparing RNA sequencing libraries is one of the many methods to determine which part of the genome is expressed, since examining the sequences of RNA gives us a snapshot of the cell at any given moment in time. Often, making RNA-seq libraries involves converting raw RNA into DNA, which is a more stable macromolecule. Adaptors are then tagged onto the cDNA for bridge amplification. By measuring the light intensity and emitted wavelength of fluorescently tagged nucleotides, the DNA can be sequenced [10].

After sequencing the DNA, the sequences need to be mapped to a reference genome. Differential gene expression analysis is primarily interested in determining the relative DNA differences in expression levels between reads. However, inherent bias in the data needs to be corrected. First, longer reads will tend to have more transcripts (the longer the read, the higher probability that a transcript will match to the read on the reference genome). Furthermore, the library preparation with the higher concentration will have more number of transcripts. Count normalization, which performs various statistical algorithms, can account for this inherent bias, giving a more accurate measure of the relative differences in the gene expression of the reads [11].

To determine whether a difference in the expression levels between genes exists, a statistical test, typically a p test, is performed. By comparing the p values, for example, for the different library preparations of cells over various stages of potency, the down regulation and up regulation of certain genes can be determined [12]. So far, research indicates that the differences in the neocortex of primates stem from differential gene expression in the stem cells of the VZ. The information encoded in the regulatory genes is carried to the cortical plate by radial glial cells [13].

Ultimately, the differences in cognitive abilities and social behaviors between humans and chimpanzees can be explained by two major factors at this point. First, larger brain development during the early stages of embryonic growth in humans results in increased cerebral volume, but in nonhuman primates, brain development occurs to a much lesser extent. Second, images of the human brain display a greater number of neural connective fibers than images of nonhuman primates, which may account for our higher level of cognitive ability.

By further examining the timing and levels of expression in a variety of genes and by analyzing brain images during early embryonic development, scientists hope to find the answer to the question that remains partially unanswered: what makes humans unique?

References:

  1. Anders, Simon, and Wolfgang Huber. “Differential expression of RNA-Seq data at the gene level–the DESeq package.” Fred Hutchinson Cancer Research Center. Accessed August 11, 2015. http://cobra20.fhcrc.org/packages/release/bioc/vignettes/DESeq/inst/doc/DESeq.pdf.
  1. “The Cambridge Declaration of Consciousness.” Your Brain and You: Philosophy of mind without jargon. Last modified August 24, 2012. Accessed August 27, 2015. http://politicalblindspot.com/prominent-scientists-sign-a-declaration-of-animal-consciousness/.
  1. “Brain Structures and Their Functions.” Serendip Studio. Last modified 1994. Accessed September 3, 2015. http://serendip.brynmawr.edu/bb/kinser/Structure1.html.
  1. Rakic, Pasko. “Evolution of the Neocortex: Perspective from Developmental Biology.” National Center for Biotechnology Information, October 2009, 724-35. Accessed June 4, 2015. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913577/#R125.
  1. Ibid.
  1. Lui, Jan H., David V. Hansen, and Arnold R. Kriegstein. “Development and Evolution of the Human Neocortex.” Science Direct 146, no. 1 (July 8, 2011): 18-36. Accessed June 9, 2015. http://www.sciencedirect.com/science/article/pii/S0092867411007057.
  1. Rakic, Pasko. “Evolution of the Neocortex: Perspective from Developmental Biology.” National Center for Biotechnology Information, October 2009, 724-35. Accessed June 4, 2015. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913577/#R125.
  1. King, Mary-Claire, and A. C. Wilson. “Evolution at Two Levels in Humans and Chimpanzees.” Science 188, no. 1 (April 11, 1975): 107-16. Accessed June 2, 2015. http://links.jstor.org/sici?sici=0036-8075%2819750411%293%3A188%3A4184%3C107%3AEATLIH%3E2.0.CO%3B2-0.
  1. Englund, Chris, Andy Fink, Charmaine Lau, Diane Pham, Ray A. M. Daza, Alessandro Bulfone, Tom Kowalczyk, and Robert F. Hevner. “Pax6, Tbr2, and Tbr1 Are Expressed Sequentially by Radial Glia, Intermediate Progenitor Cells, and Postmitotic Neurons in Developing Neocortex.” The Journal of Neuroscience 25, no. 1 (January 5, 2005): 247-51.
  1. Parkhomchuk, Dmitri, Tatiana Borodina, Vyacheslav Amstislavskiy, Maria Banaru, Linda Hallen, Sylvia Krobitsch, Hans Lehrach, and Alexey Soldatov. “Transcriptome analysis by strand-specific sequencing of complementary DNA.” Oxford Journals 37, no. 18 (June 30, 2009). Accessed July 7, 2015. http://nar.oxfordjournals.org/content/37/18/e123.full.
  1. Anders, Simon, and Wolfgang Huber. “Differential expression of RNA-Seq data at the gene level–the DESeq package.” Fred Hutchinson Cancer Research Center. Accessed August 11, 2015. http://cobra20.fhcrc.org/packages/release/bioc/vignettes/DESeq/inst/doc/DESeq.pdf.
  1. Ibid.

Image References:

[1] Accessed June 28, 2015.

http://www.nature.com/nrn/journal/v8/n6/fig_tab/nrn2151_F1.html

 

Sohil Patel is currently a senior at The Harker School in San Jose, California. He is interested in studying diverse biology and chemistry topics, especially genetics. An avid bird watcher, he loves strolling through his neighborhood park and observing nature’s chemistry firsthand.​

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