YSM Issue 91.1

More documents

Recommendations

Info

FOCUS evolutionary biology DIVERGENCE The Molecular and Cellular Basis of the Human Brain Evolution by Anna Sun || art by Emma Healy Millions of years have passed since humans parted ways with our closest nonhuman primates on the evolutionary pathway. During this time, humans have developed languages and writing skills, harnessed fire and begun cooking, created innovative technologies that now govern our daily lives, and even studied how life itself works. So why have no other nonhuman primates ever rivaled our level of cognitive ability? In hopes of answering that very question, much debate among scientists today centers around the differences between the brain structures of humans and nonhuman primates. While some argue that the larger size of the human brain alone is responsible for higher-order thinking, others insist that there is more to the story. Perhaps in addition to increased size, the connections between cells and the different cells themselves provide a better explanation. André Sousa and Ying Zhu, researchers at the Yale School of Medicine, analyzed tissue samples from sixteen regions of the brain to further investigate the cellular and molecular differences between human and nonhuman primate brains. Examining individual gene expression differences in the brains of chimpanzees, macaques, and humans, these researchers discovered human-specific differences in the expression of the TH gene responsible for dopamine production and the MET gene that is related to Autism Spectrum Disorder, gaining insight into the basis of certain neurological and psychiatric disorders. Our closest relatives In order to determine human-specific differences in the brain structures, the researchers chose to study chimpanzees, our closest living relative, as well as the rhesus macaque, one of the most commonly studied nonhuman primates. “Ideally, the easiest way to study human brain evolution would be to analyze the brains of all extinct human species,” Sousa remarked. However, since the brain does not fossilize, he and his colleagues instead had to compare the human brain with the brains of our closest living relatives to determine which features are most likely human-specific. For ethical reasons, they could only use postmortem tissue for direct molecular experimentation. The researchers particularly analyzed the upregulation or downregulation of 22 Yale Scientific Magazine March 2018 www.yalescientific.org
evolutionary biology FOCUS genes, to correspondingly compare increased or decreased gene expressions in different parts of the brain in the different species studied. “What drives these differences in gene expression are often changes in regulatory non-coding regions,” explains Sousa. “Additionally, mutations in non-coding regions of DNA don’t change the protein product, but rather change when, where, and how much is produced.” Because humans and chimpanzees diverged from a common ancestor more recently than they did from macaques, the researchers were able to use these three branches of a much more extensive evolutionary tree in order to narrow down the origins of a modified gene. For example, if a specific gene appeared to be upregulated in humans but downregulated in both chimpanzees and macaques, then this would indicate a human-specific change. Similarly, if a gene was upregulated in humans and macaques, but downregulated in chimpanzees, then this would demonstrate a chimpanzee-specific change. This gene regulation would then correspond to an increase or decrease in the production of proteins in cells and thus a change in the trait, or phenotype, displayed by each species. A glance at brain structure The human brain is about three times larger than the chimpanzee brain. The primary assumption is that a bigger brain should be able to hold more information and form more complex circuits between nerve cells. “We believe that instead of one big change in brain structure that accounts for a lot of differences, there are actually many small but distinct differences in human brains that “ This image shows the molecular characterization of TH+ cells. Instead of one big change in brain structure that accounts for a lot of differences, there are actually many small but distinct differences in human brains that add together to make big differences. www.yalescientific.org ” - André Sousa add together to make big differences, for example, in cognition,” Sousa said. Uncertain of where they would find the most differences in the brains of the three species, the researchers approached this study without a main brain region of interest. Because the neocortex is known predominantly for its role in higher cognitive function, they hypothesized that the greatest number of differences across the species would be located in this region. Their data demonstrated that, as expected, most genes were similar and therefore conserved among humans, chimpanzees, and macaques. However, the most interspecies differences in changes in gene expression were actually discovered not in the neocortex but in the striatum, a region of the brain primarily involved in voluntary movement, planning, and reward. “This is likely because it is a transition station between the neocortex and other regions of the brain, so changes in this region may also lead to changes in the neocortex,” Zhu reasoned. The key is in dopamine IMAGE COURTESY OF ANDRE MIGUEL SOUSA All primates have dopamine, a crucial neurotransmitter responsible for motor control and emotional responses. The researchers discovered that the TH gene, responsible for the production of dopamine, was more expressed in the human striatum than in the striata of chimpanzees and macaques, which indicates that humans most likely have more dopamine in the striatum than in the other species studied. “There are two possible explanations for this observation,” Sousa said. “First—there are exactly the same number of TH cells among the three species, but each human cell is producing considerably more dopamine; or second—humans have more TH cells than chimpanzees and macaques.” Because these comparisons were made at the tissue level, the researchers performed cellular-level analysis and were able to conclude that the latter case was true: humans have more TH cells in the striatum than the other two species. In fact, chimpanzees and the other non-human African great apes (bonobos and gorilas) March 2018 Yale Scientific Magazine 23
Page 1: Yale Scientific Established in 1894
Page 4 and 5: Q&A HOW COLD CAN WATER GET? By Alic
Page 6 and 7: NEWS in brief THE ROLE OF ERROR IN
Page 8 and 9: NEWS psychology KNOW TOO MUCH? The
Page 10 and 11: NEWS medicine ERADICATING HIV Targe
Page 12 and 13: FOCUS biotechnology Sneaking Organs
Page 14 and 15: FOCUS biomedical engineering perfus
Page 16 and 17: FOCUS organic chemistry Within our
Page 18 and 19: Surprises in the CLOUDS Understandi
Page 20 and 21: FOCUS neuroscience BRAVING THE COLD
Page 24 and 25: FOCUS evolutionary biology have no
Page 26 and 27: FEATURE environmental science IT’
Page 28 and 29: DISEASE DOUBLE WHAMMY Crohn’s dis
Page 30 and 31: BIG BANG GIVE ME A TWIRL by Urmila
Page 32 and 33: FEATURE biomedical engineering Defe
Page 34 and 35: FEATURE environmental science COUNT
Page 36 and 37: COLIN HEMEZ (ES ‘18) THINKING DEE
Page 38 and 39: Science in the Spotlight The Evolut
Page 40: C A R T O O N S TEARS FELLOWSHIPS W

YSM Issue 91.1

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?