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Jesal Solanki Thursday 3:00pm Research paper topic and annotated bibliography My research paper topic is “Is the human brain still evolving” Easton, John. "University of Chicago Researchers Find Human Brain Still Evolving." - The University of  	Chicago Medicine. N.p., n.d. Web. 14 Sept. 2014. This article describes the genes that are contributing to the evolution of the human brain as mutations. The mutations don’t cause evolution on a species levels but instead some individual are exposed to the mutation first. Natural selection is said to favor the mutation and increases chance of survival in the constant changing environment. Gilbert, Sandra L., William B. Dobyns, and Bruce T. Lahn. "Opinion: Genetic Links between Brain 	Development and Brain Evolution."Nature Reviews Genetics 6.7 (2005): 581-90. Web. 14 Sept. 2014. This article stresses the further importance of microcephaly defines it as a defect that that has reduced brain size and the evolutionary past. Microcephaly continues to regulate brain size in the continuing evolution of the human brain. "Research News: Human Brain Is Still Evolving | Howard Hughes Medical Institute." HHMI.org. N.p., 5 Sept. 2005. Web. 14 Sept. 2014. This article outlines the research of Bruce Lahns team on the studies done to examine the difference in genomic structure of the human brain compared to that of other primates. The research mostly highlight the discovery of the ASPM and Microcephalin genes which may have risen due to a mutation. The genes may be a part of a larger genome that could be the basis for the higher cognitive functions of the human brain. Stern, Rowena, and Christopher Geoffrey Woods. "Evolutionary Genetics: Is Brain Evolution Still Continuing in Modern Humans?" European Journal of Human Genetics 14.7 (2006): 799-800. Web. 14 Sept. 2014. Highlights the studies done by Bruce Lahn and researchers at the University of Chicago. It arcticle discusses the difference between the size of the human brain compared to the brain size of other animals. The larger brain size of humans means that it is more costly in energy. The article also highlights the research on the microcephalin gene and how its constant evolution causes changes in modern human brain function. Zhang, J. "Evolution of the Human ASPM Gene, a Major Determinant of Brain Size." Genetcis (2003): n. pag. PubMed. Web. 14 Sept. 2014. Discussion of the ASPM gene which is a major determinant of human brain size. This gene is linked to the emergence of higher cognitive function. Associated with the evolutionary split between humans and chimpanzees.

Edits to exiting page "Evolution of the Brain"
Bruce Lahn, the senior author at the Howard Hughes Medical Center at the University of Chicago and colleagues have suggested that there are specific genes that control the size of the human brain. These genes continue to play a role in brain evolution, implying that the brain is continuing to evolve. The study began with the researchers assessing 214 genes that are involved in brain development. These genes were obtained from humans, macaques, rats and mice. Lahn and the other researchers noted points in the DNA sequences that caused protein alterations. These DNA changes were then scaled to the evolutionary time that it took for those changes to occur. The data showed the genes in the human brain evolved much faster than those of the other species. Once this genomic evidence was acquired, Lahn and his team decided to find the specific gene or genes that allowed for or even controlled this rapid evolution. Two genes were found to control the size of the human brain as it develops. These genes are Microcephalin and Abnormal Spindle-like Microcephaly (ASPM). The researchers at the University of Chicago were able to determine that under the pressures of selection, both of these genes showed significant DNA sequence changes. Lahn's earlier studies displayed that Microcephalin experienced rapid evolution along the primate lineage which eventually led to the emergence of Homo sapiens. After the emergence of humans, Microcephalin seems to have shown a slower evolution rate. On the contrary, ASPM showed its most rapid evolution in on the later years of human evolution once the divergence between chimpanzees and humans had already occurred. .

Each of the gene sequences went through specific changes that lead to the evolution of humans from ancestral relatives. In order to determine these alterations, Lahn and his colleagues used DNA sequences from multiple primates then compared and contrasted the sequences with those of humans. Following this step, the researchers statistically analyzed the key differences between the primate and human DNA to come to the conclusion, that the differences were due to natural selection. The changes in DNA sequences of these genes accumulated to bring about a competitive advantage and higher fitness that humans possess in relation to other primates This comparative advantage is coupled with a larger brain size which ultimately allows the human mind to have a higher cognitive awareness. .

Final Draft
Throughout the study of human evolution, scientists have identified specific traits that distinguish humans from other species that share a common ancestor. These characteristics include many anatomical and behavioral alterations. However, the most obvious and important attribute for this differentiation is none other than the capabilities of the human brain. The complexity of the brain allows humans to possess higher cognitive functions compared to other primates and mammals. These high order functions contribute to certain unique capabilities, such as utilization of a written language or the early development of agriculture (Hawks 2014). However, the way the human brain evolved such complexity and the factors that allowed this occurrence is still perplex many researchers today. In order to assess the components that brought about this higher function, we must go back to the evolutionary divergence between humans and other nonhuman primates. Then, we will examine two specific genes that suggest the human brain never stopped evolving and continues to grow more complex every day. Much of the discoveries and theories of early human development are based on fossil discoveries of ancient relatives of modern Homo sapiens. One such ancient species is Australopithecus afarensis. Before the emergence of the modern day Homo sapiens, many characteristics of these ancient relatives were similar to the traits of early and modern apes. By using the assessments of ancient skull fossils, anthropologists were able to predict the size of the brain based on the internal skull volume of Australopithecus afarensis. The volume of the internal skull cavity was found to be similar to that of modern chimpanzees and gorillas (Hawks 2014). However, about two million years ago the human brain diverted from this characteristic and the brain of this ancient relative began to show subtle changes in size and shape. Ancient skull molds show that alternations in specific parts of the brain began to take place. For instance, the cerebral cortex began to expand and areas within the cortex began to exhibit changes (Bradbury 2005). Later in the timeline of human brain evolution, scientists began so see major “jumps” in brain size with the emergence of the first species of the Homo genus. These “jumps” can be described as a static brain size for long periods of time followed by sudden rapid change. The fossils of the Homo habilis displayed larger volumes of the near frontal cortex, which is responsible for language (Hawks 2014). Following the jumps, the brain began to slowly yet consistently increase in size and complexity for the next 500,000 years. During this time, the individuals in these species were developing skills such as problem solving, social interaction and depth perception (Hawks 2014). This lengthy progression eventually led to the human brain that we are familiar with today. Most of the cognitive attributes that humans possess which differ from other mammals are due to the increased size and complexity of the brain. In fact, a team of researchers at the University of Chicago stated that the selection for higher levels of intelligence is stronger in humans compared to selection for intelligence in other mammals (Dorus et. al. 2004). Although this apparent selection for complexity occurred, what are the molecular and genetic components that are responsible? This can be further analyzed by looking at the modern day evolution of the human brain and the research being done to answer questions about the past and present. Bruce Lahn, the senior author at the Howard Hughes Medical Center at the University of Chicago, has made many assessments that have, perhaps, given an answer to some questions involving human brain evolution. Lahn and colleagues have suggested that there is a specific gene that control the size of the human brain. This gene continues to play a role in brain evolution, implying that the brain is continuing to evolve. The study began with the researchers assessing 214 genes that are involved in brain development. These genes were obtained from humans, macaques, rats and mice. Lahn and the other researchers noted points in the DNA sequences that caused protein alterations. These DNA changes were then scaled to the evolutionary time that it took for those changes to occur. The data showed the genes in the human brain evolved much faster than those of the other species. Once this genomic evidence was acquired, Lahn and his team decided to find the specific gene or genes that allowed for or even controlled this rapid evolution. Two genes were found to control the size of the human brain as it develops. These genes are Microcephalin and Abnormal Spindle-like Microcephaly (ASPM). The researchers at the University of Chicago were able to determine that under the pressures of selection, both of these genes showed significant DNA sequence changes through microevolution. Lahn's earlier studies displayed that Microcephalin experienced rapid evolution along the primate lineage which eventually led to the emergence of Homo sapiens. After the emergence of humans, Microcephalin seems to have shown a slower evolution rate. On the contrary, ASPM showed its most rapid evolution in on the later years of human evolution once the divergence between chimpanzees and humans had already occurred (Dorus et. al. 2004). Each of the gene sequences went through specific changes that lead to the evolution of humans from ancestral relatives. In order to determine these alterations, Lahn and his colleagues used DNA sequences from multiple primates then compared and contrasted the sequences with those of humans. Following this step, the researchers statistically analyzed the key differences between the primate and human DNA to come to the conclusion, that the differences were due to natural selection. The changes in DNA sequences of these genes accumulated to bring about a competitive advantage and higher fitness that humans possess in relation to other primates (Evans et. al. 2005). This comparative advantage is coupled with a larger brain size which ultimately allows the human mind to have a higher cognitive awareness. A researcher from the University of Michigan, Jianzhi Zhang, also sought an answer to the question of what molecular components control the size and complexity of the human brain. Zhang focused his research specifically on ASPM. He studied the role of ASPM in Microcephaly, a human disease that is defined by a major decrease in brain size. The disease is caused by a nonsense mutation on the DNA sequence of the ASPM gene causing a reduction of the brain size. After being able to determine that ASPM was a key gene in controlling the size and complexity of the Human brain, Zhang evaluated its role in evolutionary history. Like Lahn’s conclusion, Zhang was also able to determine that ASPM went through accelerated evolution due to Darwinian selection after the divergence between humans and chimps. He then suggested that the rapid evolutionary changes slowed down after the separation between modern non-Africans and ancient Africans (Zhang 2006). So far discussions have taken place on how the human brain has come to be what it is today. However, what mechanisms are currently present in the human brain that allows it to continue to evolve? Or if it still is evolving for that matter. Researchers at the Hughes Medical Institute in Chicago decided to see if the evolutionary patterns that took place millions of years ago are still present within the genes of modern day populations. The research team began by sequencing both microcephalin and ASPM in 90 ethnically diverse individuals (Stern et. al. 2006). Each individual had distinct blocks of polymorphisms that differed from other individuals in the test. These blocked polymorphisms were referred to as haplotypes. Each haplotype was a distinct gene variant. The haplotype was then broken down into related variant group called haplogroups. In both genes one of these haplogroups displayed a higher frequency than predicted or expected by random chance. They named this haplogroup D. Then the researchers used the frequencies of haplogroup D to compare the different amounts within different ethnic groups. The research team was able to distinguish that individuals who contained high frequencies of haplogroup D in ASPM were more likely to be from Europe, North Africa, South Asia and the Middle East. Low frequencies of haplogroup D in ASPM were marked in individuals from East Asia, sub- Sahara Africa, and New World Indians. In microcephalin, higher amounts of haplogroup D were more apparent in populations outside of the African continent (Evans et. al. 2005). Then using statistical analysis Lahn was able to determine that the Microcephalin haplogroup D appeared in the human brain about 37,000 years ago while haplogroup D in ASPM first emerged only 5,800 years ago (Evans et. al. 2005). This data was used to determine that a high frequency of haplogroup D in Microcephalin is related to the appearance of modern humans and that haplogroup D in ASPM is related to the time when agriculture and a written language emerged (Gilbert et. al. 2005). This trend showed that the brain is evolving through selection based on environmental factors. The brain evolves at different rates depending on the region that one lives in then evolves according to the necessities to survive in that location. However, does this mean that the human brain is more evolved in some regions of the world compared to others? The answer to this would be no. Researchers believe that other genes interact with ASPM and Microcephalin and many different aspects must be considered to even begin to fathom that some regions of the world have more evolved individuals compared to others. (Merkel-Bobrov et. al. 2007). The evolution of the brain is a large novel that researchers have just begun to read. There are many more aspects to the human brain evolution that still need to be discovered. Not to mention that the future of the human brain is probably the biggest mystery itself. Through the genes, Microcephalin and ASPM, researchers are able to track the evolution of the size and complexity of the human brain. With this, they are able to safely say that the human brain is, indeed, evolving and will continue to evolve for as long as the human species survives.

References Bradbury, J. Molecular Insights into Human Brain Evolution. 2005. PLoS Biol.3(3):e50 Gilbert, S. L., Dobyns W. B. and Lahn B. T. 2005 Genetic Links between Brain Development and Brain Evolution. Nat Rev Genet.6(7):581-90. Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L., Mahowald M., Wyckoff G.J., Malcolm C.M., Lahn B.T. 2004. Accelerated evolution of nervous system gene in the origin of homosapiens. Cell. 119(7):1027-40. Evans P.D., Gilbert S.L, Mekel-Bobroz N., Vallender E.J., Anderson J.R. Vaez-Azizi L.M., Tishkoff S.A., Hudson R.R. and Lahn B.T. 2005. Microcephalin, a Gene Reulating Brain Size, Continues to Evolve Adaptively in Humans. Science 309(5741):1717-20 Hawks, J. No, Humans Have Not Stopped Evolving. 2014. Sci. Am. Glo. Mekel-Bobrov N., Posthuma D., Gilbert S.L., Lind P., Gosso M..F., Luciano M., Harris S.E., Bates T.C., Polderman T.J., Whalley L.J., Fox H., Starr J.M. Evans P.D., Montgomery G.W., Fernandes C., Heutink P., Martin N. G., Boosma D.I., Deary I.J., Wright M.J., de Geus E.J., Lahn B.T. The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum. Mol. Genet. 16(6):600-8 Stern, R and Woods C.G. 2006. Evolutionary Genetics: Is Brain Evolution Still Continuing in Modern Humans? Eur J Hum Genet.14(7):799-800. Zhang, J. 2006. Evolution of the human ASPM gene, a major determinant of brain size Genetics165(4):2063-70.