This blog is devoted to BIOL 6988, a graduate level seminar in the biological sciences at Youngstown State University. While targeted towards graduate students, BIOL 6988 actively incorporates undergraduate participants in their scholastic endeavors in the biological sciences. This blog is intended as a educational tool not just for YSU students and faculty, but for anyone who wishes to contribute to an active-learning environment.
So, my good buddy Dr. Gary Walker spoke this past week, correct? I wouldn't know since I couldn't be there. I believe it's Mike's turn to start the discussion. Tell us how it was, Mike!!
Dr. Walker gave an awesome presentation that focused around the protein Titin. Titin is a member of the family of Giant Muscle Proteins and is the largest protein found in nature at this time. Subsequently, the titin gene is also the largest gene to date and found on the short arm of chromosome 2. Titin is a myosin binding protein which means it supports the myosin fibers inside of muscle. Myosin along with Actin, are the major components of the sarcomere, the structure that causes the contraction of muscles. Titin, being a myosin binding protein, helps stabilize the sarcomere and ensure that there is smooth expansion and contraction of the multiple fibers in an effort to avoid damaging the muscle. One of the more interesting aspects of Titin is its evolution. Titin is a huge protein yet, has a region (A band) that is highly conserved in all different forms implying that mutation in this area is unfavorable in nature. Dr. Walker’s investigations into Titin have lead his research to focus on evaluating the possibility that Titin has a role in the regulation of muscle development. What types of genes or proteins do you think might be among the most highly conserved and why?
Dr. Walker's lecture certainly refreshed my memory on on many topics that I learned as a young undergraduate. His research goals are incredible and I hope him and his colleagues are successful as it would have a profound impact on the lives of many individuals. During my research I discovered there are regions in the human genome that are considered "ultra-conserved" regions in the human genome. These regions are have remained unchanged through millions of years of evolutionary history and are present in most other species of the vertebrata subphylum. Interesting however, only a small number of elements in these regions are protein coding. These ultra-conserved regions tend to be located in regions associated with transcription and gene regulation, which is logical as such foundational functions are essential for an individual's organisms development and survival.
Conserved genes, are the genes that have remained unchanged over a long period of time in evolutionary history. This implies that the genes sequence are very vital to life and mutation in this region leads to non – viable life form, or in a form that is eliminated through natural selection. In my view part of the genome having that level of conservation is the DNA that codes for ribosomes and their function in the cells of every organisms. Ribosomes are made of RNA and proteins. They function in translating genetic code during protein synthesis in all cells. Being very essential to life, ribosomal sequences are highly conserved. The DNA sequences that code for ribosomal RNA contain long stretches of bases that are perfectly conserved throughout evolution. Ribosomal RNA is ancient and is common to all species
“There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.” Example: uc.283 lncRNA, which is highly specific for pluripotent stem cells. In addition, uc.283-plus lncRNA is highly expressed in some cancers.
One of the most highly conserved proteins found in eukaryotes and some archaea are histones. These proteins are made up of 2 sets of four subunits (H2A, H2B, H3, and H4) making up the core histone. They also contain one H1 subunit that intertwines with DNA. Histones are extremely important in chromatin structure. DNA is wrapped around this protein forming nucleosomes and these then fold to form higher structures forming the chromosomes found in the nucleus of most eukaryotic species. There are very few changes in amino acids and those changes form different subtypes of histones that are differ in their ability to condense chromatin. The need for this protein to be highly conserved between species is that the cells need functional proteins in order to compact the very large DNA into something manageable in order for proper cell division to occur. Prokaryotes have a much smaller genome that does not need to be compacted it in order for the cell to repoduce. It is very likely that lacking histones, or having altered versions of them, prevents the folding of the DNA. Lack of folding can cause certain parts of the DNA to be lost or cut out during cell division which can form cells that lack very important parts that will more likely than not be aborted or cease to function. Cells that cease to function early in its life cycle or do not form properly will not be able to reproduce and pass on the altered changes in amino sequences that resulted in the faulty histones to other cells.
According to the research article linked at the end of this paragraph, some of the most highly conserved genomic regions across diverse microbial and non-microbial taxa are the 16S and 23S ribosomal genes. Further analysis shows particular tRNA genes, nucleotide binding domains of ATP-binding cassette transporters, and other sequences are nearly universal. These highly conserved genes and proteins are such because they are required for cells to replicate and divide and for life to be sustained.
Paired box protein (PAX6) is a protein regulates development of eyes and central nervous system. Many researches led to the identification of PAX6 gen were examined in mammals and insects and showed that PAX6 is highly conserved among vertebrates and lower animals. PAX6homologues found in rats, zebra fish, mice and the fly drosophila with the %90 amino acid sequence identity(Quiring, et al. 1994);. Also, mouse and human PAX6 have identical amino acid sequences.
Dr. walker gave a great presentation. I really found it fascinating how some of his students are trying to combine 3D printing with muscle cells. This would be a great advantage in future medicine. I have heard of something similar for skin cells where they can replace burned skin with these new cells which will proliferate to repair damaged skin. Reserved gene regions indicate the importance in the cell's functioning and processing. Mutations in dystrophin production is a cause of the severe disease called muscular dystrophy. This disease causes muscle atrophy.
Calmodulin is highly conserved protein and plays important role in muscle action. CaM mediates many important processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. CaM is expressed in many cell types and can have different locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes. Many of the proteins that CaM binds are unable to bind calcium themselves, and use CaM as a calcium sensor and signal transducer.\Calmodulin is a small, highly conserved protein approximately 148 amino acids long. Other proteins can bind calcium, but Calmodulin is one of the most highly used and conserved proteins.
Dr. walker gave an excellent presentation on his research on Titin, i was surprised to learn that it was such a large protein and that it was such a conserved protein. However upon reflection this makes sense, as Titin regulates muscle expansion and contraction which is an extremely important mechanism. I found that the genes encoding for tRNA are also relatively conserved across Archea, Eukarya and Bacteria. I think this sequence is relatively conserved because it is heavily involved with the mechanism of constructing proteins which are essential to many things in all domains. Proteins are involved with exoskeletons, enzymes, mictrotubules etc Hence since proteins are involved in almost every important facet of organisms, it makes sense that the mechanism to construct them is highly conserved, because alterations in these genes may lead to organisms inability to produce proteins and they would not exist and lose out to evolution. So in closing, having conserved tRNA genes probably led to an increase in fitness and that is why we can observe the conservation of the genes today.
Dr. Walker gave an awesome presentation that focused around the protein Titin. Titin is a member of the family of Giant Muscle Proteins and is the largest protein found in nature at this time. Subsequently, the titin gene is also the largest gene to date and found on the short arm of chromosome 2. Titin is a myosin binding protein which means it supports the myosin fibers inside of muscle. Myosin along with Actin, are the major components of the sarcomere, the structure that causes the contraction of muscles. Titin, being a myosin binding protein, helps stabilize the sarcomere and ensure that there is smooth expansion and contraction of the multiple fibers in an effort to avoid damaging the muscle. One of the more interesting aspects of Titin is its evolution. Titin is a huge protein yet, has a region (A band) that is highly conserved in all different forms implying that mutation in this area is unfavorable in nature. Dr. Walker’s investigations into Titin have lead his research to focus on evaluating the possibility that Titin has a role in the regulation of muscle development.
ReplyDeleteWhat types of genes or proteins do you think might be among the most highly conserved and why?
Dr. Walker's lecture certainly refreshed my memory on on many topics that I learned as a young undergraduate. His research goals are incredible and I hope him and his colleagues are successful as it would have a profound impact on the lives of many individuals.
ReplyDeleteDuring my research I discovered there are regions in the human genome that are considered "ultra-conserved" regions in the human genome. These regions are have remained unchanged through millions of years of evolutionary history and are present in most other species of the vertebrata subphylum. Interesting however, only a small number of elements in these regions are protein coding. These ultra-conserved regions tend to be located in regions associated with transcription and gene regulation, which is logical as such foundational functions are essential for an individual's organisms development and survival.
Conserved genes, are the genes that have remained unchanged over a long period of time in evolutionary history. This implies that the genes sequence are very vital to life and mutation in this region leads to non – viable life form, or in a form that is eliminated through natural selection. In my view part of the genome having that level of conservation is the DNA that codes for ribosomes and their function in the cells of every organisms.
ReplyDeleteRibosomes are made of RNA and proteins. They function in translating genetic code during protein synthesis in all cells. Being very essential to life, ribosomal sequences are highly conserved. The DNA sequences that code for ribosomal RNA contain long stretches of bases that are perfectly conserved throughout evolution. Ribosomal RNA is ancient and is common to all species
“There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.”
ReplyDeleteExample: uc.283 lncRNA, which is highly specific for pluripotent stem cells. In addition, uc.283-plus lncRNA is highly expressed in some cancers.
https://users.soe.ucsc.edu/~jill/ultra.html
One of the most highly conserved proteins found in eukaryotes and some archaea are histones. These proteins are made up of 2 sets of four subunits (H2A, H2B, H3, and H4) making up the core histone. They also contain one H1 subunit that intertwines with DNA. Histones are extremely important in chromatin structure. DNA is wrapped around this protein forming nucleosomes and these then fold to form higher structures forming the chromosomes found in the nucleus of most eukaryotic species. There are very few changes in amino acids and those changes form different subtypes of histones that are differ in their ability to condense chromatin. The need for this protein to be highly conserved between species is that the cells need functional proteins in order to compact the very large DNA into something manageable in order for proper cell division to occur. Prokaryotes have a much smaller genome that does not need to be compacted it in order for the cell to repoduce. It is very likely that lacking histones, or having altered versions of them, prevents the folding of the DNA. Lack of folding can cause certain parts of the DNA to be lost or cut out during cell division which can form cells that lack very important parts that will more likely than not be aborted or cease to function. Cells that cease to function early in its life cycle or do not form properly will not be able to reproduce and pass on the altered changes in amino sequences that resulted in the faulty histones to other cells.
ReplyDeleteAccording to the research article linked at the end of this paragraph, some of the most highly conserved genomic regions across diverse microbial and non-microbial taxa are the 16S and 23S ribosomal genes. Further analysis shows particular tRNA genes, nucleotide binding domains of ATP-binding cassette transporters, and other sequences are nearly universal. These highly conserved genes and proteins are such because they are required for cells to replicate and divide and for life to be sustained.
ReplyDeletehttp://arep.med.harvard.edu/pdf/Isenbarger08.pdf
Paired box protein (PAX6) is a protein regulates development of eyes and central nervous system. Many researches led to the identification of PAX6 gen were examined in mammals and insects and showed that PAX6 is highly conserved among vertebrates and lower animals. PAX6homologues found in rats, zebra fish, mice and the fly drosophila with the %90 amino acid sequence identity(Quiring, et al. 1994);. Also, mouse and human PAX6 have identical amino acid sequences.
ReplyDeleteDr. walker gave a great presentation. I really found it fascinating how some of his students are trying to combine 3D printing with muscle cells. This would be a great advantage in future medicine. I have heard of something similar for skin cells where they can replace burned skin with these new cells which will proliferate to repair damaged skin. Reserved gene regions indicate the importance in the cell's functioning and processing. Mutations in dystrophin production is a cause of the severe disease called muscular dystrophy. This disease causes muscle atrophy.
ReplyDeleteCalmodulin is highly conserved protein and plays important role in muscle action. CaM mediates many important processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. CaM is expressed in many cell types and can have different locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes. Many of the proteins that CaM binds are unable to bind calcium themselves, and use CaM as a calcium sensor and signal transducer.\Calmodulin is a small, highly conserved protein approximately 148 amino acids long. Other proteins can bind calcium, but Calmodulin is one of the most highly used and conserved proteins.
ReplyDeletehttps://en.wikipedia.org/wiki/Calmodulin
Dr. walker gave an excellent presentation on his research on Titin, i was surprised to learn that it was such a large protein and that it was such a conserved protein. However upon reflection this makes sense, as Titin regulates muscle expansion and contraction which is an extremely important mechanism.
ReplyDeleteI found that the genes encoding for tRNA are also relatively conserved across Archea, Eukarya and Bacteria. I think this sequence is relatively conserved because it is heavily involved with the mechanism of constructing proteins which are essential to many things in all domains. Proteins are involved with exoskeletons, enzymes, mictrotubules etc Hence since proteins are involved in almost every important facet of organisms, it makes sense that the mechanism to construct them is highly conserved, because alterations in these genes may lead to organisms inability to produce proteins and they would not exist and lose out to evolution. So in closing, having conserved tRNA genes probably led to an increase in fitness and that is why we can observe the conservation of the genes today.
http://arep.med.harvard.edu/pdf/Isenbarger08.pdf