A group of researchers from the UNC School of Medicine is employing evolutionary genomics to gain insights into human diseases. Their focus lies on highly conserved genes that have remained unchanged throughout mammalian evolution. This unique approach enables the identification of genetic alterations in these genes, shedding light on the origins of psychiatric and neurological disorders. By manipulating specific DNA sequences, researchers may potentially mitigate the impact of genetic diseases.
In a groundbreaking effort, a team of scientists has developed a comprehensive resource for researchers to explore the origins of human diseases with a high genetic risk.
Numerous scientific studies have been conducted to unravel the genetic basis of common human traits, encompassing physical and mental characteristics ranging from eye color to intelligence and various illnesses.
Dr. Patrick Sullivan, a distinguished professor of Psychiatry and Genetics at the University of North Carolina (UNC) School of Medicine, along with the Psychiatric Genomic Consortium, has compiled an extensive document in the journal Science. This resource empowers researchers with a novel avenue to comprehend human diseases using the powerful tool of evolutionary genomics.
Dr. Sullivan, who is also a professor at the Karolinska Institute in Stockholm, Sweden, expressed his excitement about this tool, stating, “This is a tool that can provide us with invaluable insights into human disease. By delving deep into an individual’s genome, we can gain an understanding of their ancestral history, encompassing both human and nonhuman lineages, and observe the impact of millions of years of evolution.”
Every living organism on Earth possesses DNA, the self-replicating material that serves as a blueprint for producing vital molecules, particularly proteins. It comes as no surprise that humans share 98.8% of their genetic material with their closest relatives, chimpanzees.
While certain genes have undergone evolutionary changes, others have remained conserved throughout the entire mammalian evolutionary process. These genes, known as “highly constrained” genes, exhibit remarkable genetic similarity across species such as mice, cows, dogs, cats, bats, and dolphins in many regions of the genome.
These genes unite us as mammals. Having withstood the test of evolutionary history, these unchanged genetic regions are presumed to play fundamental roles in an organism’s health and genetic makeup, as highlighted by Dr. Sullivan. He explains, “Some highly constrained genes can produce proteins that are nearly identical in both humans and mice, despite the roughly 60 million years of evolutionary divergence between the two species. This indicates the crucial functions of these proteins.”
Taking a holistic perspective enables a clearer understanding of the impact of our shared genes. Humans and other mammals share anatomical structures such as four-chambered hearts, lungs, hair or fur, skeletons, and milk-producing mammary glands. Additionally, we share similar underlying processes at a cellular level, encompassing embryology, cell growth and division, and the development and functioning of synapses that facilitate the transmission of neurological signals throughout our bodies and brains.
All of these shared characteristics are determined by our common genetic regions. Therefore, any alteration or deletion in the genes responsible for these fundamental mammalian traits can have detrimental effects on the organism.
This approach offers a new lens through which to examine the connection between human mental and physical health. For instance, when studying a patient with a neurological or psychiatric disorder, researchers can trace the condition back to a significant impact on one of the highly constrained genes critical to the nervous system, brain structure, or synapses.
To identify the genetic risk for a disease, many researchers have relied on genome-wide association studies (GWAS). By leveraging genomic techniques and large-scale samples, researchers analyze the entire genome of diverse populations to identify genetic variations, including single nucleotide polymorphisms (SNPs), associated with a particular disease or trait.
While understanding the location of these genetic variations in the genome is crucial, comprehending the mechanisms and reasons behind their occurrence is equally valuable. Dr. Sullivan hopes that other researchers will utilize this extensive resource to draw their own conclusions regarding the genetic underpinnings of various human diseases.
Dr. Sullivan, who also serves as the director of the UNC Suicide Prevention Institute, emphasizes the significant conservation of brain-related traits. He remarks, “As it turns out, many brain traits are highly conserved. This research project has deepened my understanding of the genome and its organization. I now regularly employ this knowledge to investigate schizophrenia, suicide, depression, and eating disorders.”
This research holds promise for future studies. The successful development of a human relies on the intricate interplay of proteins and DNA sequences. Within our DNA, regulatory enhancers and regulatory promoters—short regions—play vital roles in gene regulation.
To illustrate, the process of creating a human gene can be likened to a donut factory. Regulatory enhancers control the amount of dough extruded from the machine onto the baking tray, while promoters determine when the dough is dispensed. Eventually, a fully formed gene is produced.
Researchers like Dr. Sullivan may be able to manipulate these regulatory enhancers and promoters within DNA sequences to modulate the production of proteins encoded by genes, with the aim of mitigating the effects of genetically influenced diseases.
Dr. Sullivan explains, “It might be possible to subtly manipulate the upstream regulatory regions and observe whether it has a beneficial impact.”
Reference: “Leveraging base-pair mammalian constraint to understand genetic variation and human disease” by Patrick F. Sullivan et al., Science, 28 April 2023, DOI: 10.1126/science.abn2937
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Frequently Asked Questions (FAQs) about evolutionary genomics
What is the focus of the research discussed in the text?
The research discussed in the text focuses on utilizing evolutionary genomics to understand the genetic origins of human diseases, particularly in the context of mental health conditions and neurological disorders.
What are highly constrained genes?
Highly constrained genes are genes that have remained unchanged throughout the process of mammalian evolution. They exhibit significant genetic similarity across species and are believed to play fundamental roles in the health and genetic makeup of organisms.
How can studying highly constrained genes provide insights into human diseases?
Studying highly constrained genes allows researchers to trace alterations in these genes to psychiatric and neurological disorders. By understanding the impact of these genetic variations, researchers can gain insights into various mental health conditions and potentially develop strategies to mitigate the effects of genetic diseases.
What is the significance of evolutionary genomics in this research?
Evolutionary genomics provides a powerful tool for understanding human diseases by examining genetic variations within the context of evolutionary history. It helps researchers identify shared genetic regions among mammals and comprehend the fundamental genetic processes underlying physical and mental health.
How can researchers manipulate DNA sequences to lessen the effects of genetic diseases?
Researchers can manipulate regulatory enhancers and promoters within DNA sequences to modulate the production of proteins encoded by genes. By fine-tuning gene regulation, they aim to lessen the impact of genetically influenced diseases and explore potential therapeutic interventions.
3 comments
i’m not a scientist, but i find this topic really fascinating. it’s incredible to think about how our genes have been conserved throughout evolution and how they play such important roles in our health. understanding the genetic basis of diseases could lead to better treatments and maybe even preventions in the future. science is so cool!
this reseach seems like it could be a real game changer! if they can figure out how to manipulate the DNA sequences, maybe we can find new ways to treat genetic diseases. it’s like science fiction becoming reality! can’t wait to see where this research leads.
wow this article is super interesting! i didn’t know that studying genes from different species can help us understand human diseases. i always thought genes were just for eye color and stuff like that lol. but it turns out they’re also connected to mental health conditions. amazing!