Lecture 4 - Genetics PDF

GENETICS ENGR. ARIEL M. ROSALES The Cell Cycle (and cancer) [Updated] Explore the cell cycle with the Amoeba Sisters and an important example of when it is not controlled: cancer. We have an Unlectured resource for this topic: https://www.amoebasisters.com/unlectured Expand video details for table of contents. 👇 Video also mentions cell cycle checkpoints and cell cycle control. Table of Contents: 00:00 Intro 1:00 Cell Growth and Cell Reproduction 1:42 Cancer (explaining uncontrolled cell growth) 3:27 Cell Cycle 5:26 Cell Cycle Checkpoints 6:48 Cell Cycle Regulation 8:16 G0 Phase of Cell Cycle Vocabulary in this video includes the words apoptosis, G1, S, G2, mitosis, and cytokinesis. Positive regulator proteins such as cyclins and cyclin dependent kinases are briefly mentioned as well as a negative regulator protein p53. Positive and negative regulation reference regarding cyclin types and cyclin rise/fall areas [in humans]: OpenStax, Biology. OpenStax CNX. http://cnx.org/contents/[email protected]. Are you interested in how blood supply to cancer cells may differ from blood supply to healthy cells? Learn more in this Further Reading: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661770/ The Amoeba Sisters videos demystify science with humor and relevance. The videos center on Pinky's certification and experience in teaching biology at the high school level. For more information about The Amoeba Sisters, visit: http://www.amoebasisters.com/about-us.html We cover the basics in biology concepts at the secondary level. If you are looking to discover more about biology and go into depth beyond these basics, our recommended reference is the FREE, peer reviewed, open source OpenStax biology textbook: https://openstax.org/details/books/biology Support Us? https://www.amoebasisters.com/support-us Our Resources: Biology Playlist: https://www.youtube.com/playlist?list=PLwL0Myd7Dk1F0iQPGrjehze3eDpco1eVz GIFs: https://www.amoebasisters.com/gifs.html Handouts: https://www.amoebasisters.com/handouts.html Comics: https://www.amoebasisters.com/parameciumparlorcomics Unlectured Series: https://www.amoebasisters.com/unlectured Connect with us! Website: https://www.AmoebaSisters.com Twitter: http://www.twitter.com/AmoebaSisters Facebook: http://www.facebook.com/AmoebaSisters Tumblr: http://www.amoebasisters.tumblr.com Pinterest: http://www.pinterest.com/AmoebaSister-s Instagram: https://www.instagram.com/amoebasistersofficial/ Visit our Redbubble store at https://www.amoebasisters.com/store TIPS FOR VIEWING EDU YOUTUBE VIDEOS: Want to learn tips for viewing edu YouTube videos including changing the speed, language, viewing the transcript, etc? https://www.amoebasisters.com/pinkys-ed-tech-favorites/10-youtube-tips-from-an-edu-youtuber-duo MUSIC: Music in this video is listed free to use/no attribution required from the YouTube audio library https://www.youtube.com/audiolibrary/music?feature=blog COMMUNITY: We take pride in our AWESOME community, and we welcome feedback and discussion. However, please remember that this is an education channel. See YouTube's community guidelines and how YouTube handles comments that are reported by the community. We also reserve the right to remove comments. TRANSLATIONS: Thank you so much to our translators! Turkish subtitles by Kardelen Ünalleylioğlu While we don't allow dubbing of our videos, we do gladly accept subtitle translations from our community. Some translated subtitles on our videos were translated by the community using YouTube's community-contributed subtitle feature. After the feature was discontinued by YouTube, we have another option for submitting translated subtitles here: https://www.amoebasisters.com/pinkys-ed-tech-favorites/community-contributed-subtitles We want to thank our amazing community for the generosity of their time in continuing to create translated subtitles. If you have a concern about community contributed contributions, please contact us. Cell division is a part of the cell cycle. The cell cycle is an orderly set of stages that take place between the time a cell divides and the time the resulting cells also divide. 4.1 The Cell Cycle The Stages of Interphase Interphase is divided into three stages: the G1 stage occurs before DNA synthesis, the S stage includes DNA synthesis, and the G2 stage occurs after DNA synthesis. Originally G stood for the “gaps” that occur before and after DNA synthesis during interphase. But now that we know growth occurs during these stages, the G can be thought of as standing for “growth.” During the G1 stage, a cell doubles its organelles (such as mitochondria and ribosomes), and it accumulates the materials needed for DNA synthesis. Some cells, such as nerve and muscle cells, typically pause during the cell cycle. These cells are said to have entered a G0 stage. Cells in G0 phase continue to perform their normal functions, but no longer prepare for cell division. Some cells may enter G0 phase if their DNA is damaged. If the repair of the DNA can not be completed, then the cell may undergo apoptosis. 4.1 The Cell Cycle The Stages of Interphase During the S stage, DNA replication occurs. At the beginning of the S stage, each chromosome is composed of one DNA molecule, which is called a chromatid. At the end of this stage, each chromosome consists of two sister chromatids that have identical DNA sequences. Another way of expressing this is to say that DNA replication has resulted in duplicated chromosomes. The sister chromatids remain attached until they are separated during mitosis. 4.1 The Cell Cycle The Stages of Interphase During the G2 stage, the cell synthesizes the proteins needed for cell division, such as the proteins that make up the microtubules found in the spindle apparatus Some cells, such as nerve and muscle cells, typically do not complete the cell cycle and are permanently arrested. These cells exit interphase and enter a stage called G0. While in the G0 stage, the cells continue to perform normal, everyday processes, but no preparations are being made for cell division. Cells may not leave the G0 stage without proper signals from other cells and other parts of the body. 4.1 The Cell Cycle The Mitotic Stage Following interphase, the cell enters the M (for mitotic) stage. This stage not only includes mitosis, the division of the nucleus and genetic material, but also cytokinesis, the division of the cytoplasm (which may not occur in all cells). During mitosis (covered in section 4.3), the sister chromatids of each chromosome separate, becoming daughter chromosomes that are distributed to two daughter nuclei. When cytokinesis is complete, two daughter cells are present, each identical to the original mother cell. Mammalian cells usually require only about four hours to complete the mitotic stage. 4.1 The Cell Cycle The majority of cells contain enzymes, called caspases, that bring about apoptosis. The enzymes are ordinarily held in check by inhibitors, but they can be unleashed either by internal or external signals. There are two sets of caspases. The first set, the “initiators,” receive the signal to activate the second set, the “executioners,” which then activate the enzymes that dismantle the cell. For example, executioners turn on enzymes that tear apart the cytoskeleton and enzymes that chop up DNA. 4.2 Control of the Cell Cycle Eukaryotic cells have evolved a complex system for regulation of the cell cycle. The cell cycle is controlled by both internal and external signals. The internal signals ensure that the stages follow one another in the normal sequence and that each stage is properly completed before the next stage begins. The external signals tell the cell whether or not to divide The events of the cell cycle must occur in the correct order, even if the steps take longer than normal. The red stop signs in Figure 5.1 represent three checkpoints when the cell cycle possibly stops. Researchers have identified proteins called cyclins that increase and decrease as the cell cycle continues. The appropriate cyclin has to be present for the cell to proceed from the G1 stage to the S stage and from the G2 stage to the M stage. 4.2 Control of the Cell Cycle The first checkpoint during G1 allows the cell to determine whether conditions are favorable to begin the cell cycle. The cell needs to assess whether there are building blocks available for duplication of the DNA and if the DNA is intact. DNA damage can stop the cell cycle at the G1 checkpoint. In mammalian cells, the p53 protein stops the cycle at the G1 checkpoint when DNA is damaged. First, the p53 protein attempts to initiate DNA repair, but if that is not possible, the cell enters G0 phase and undergoes apoptosis. The cell cycle stops at the G2 checkpoint if DNA has not finished replicating. This prevents the initiation of the M stage before completion of the S stage. Also, if DNA is damaged, stopping the cell cycle at this checkpoint allows time for the damage to be repaired. If repair is not possible, apoptosis occurs. 4.2 Control of the Cell Cycle Another cell cycle checkpoint occurs during the mitotic (M) stage. The cycle stops if the chromosomes are not going to be distributed accurately to the daughter cells. These checkpoints are critical for preventing cancer development. A damaged cell should not complete mitosis, but instead should undergo apoptosis. Mammalian cells tend to enter the cell cycle only when stimulated by an external factor. Growth factors are hormones that are received at the plasma membrane. These signals set into motion the events that result in the cell entering the cell cycle. For example, when blood platelets release a growth factor, skin fibroblasts in the vicinity are stimulated to finish the cell cycle so an injury can be repaired. 4.2 Control of the Cell Cycle Proto-oncogenes and Tumor Suppressor Genes Two types of genes control the movement of a cell through the cell cycle: proto-oncogenes and tumor suppressor genes. Proto-oncogenes encode proteins that promote the cell cycle and prevent apoptosis. They are often likened to the gas pedal of a car because they cause cells to continue through the cell cycle. Tumor suppressor genes encode proteins that stop the cell cycle and promote apoptosis. They are often likened to the brakes of a car because they inhibit cells from progressing through the cell cycle (Fig. 5.3a). Cancer is unregulated cell growth. Carcinogenesis, or the development of cancer, is a multistage process involving disruption of normal cell division and behavior. This typically occurs due to mutations in either proto-oncogenes or tumor suppressor genes. These genetic changes may be inherited from a parent, the result of an error in replication, or induced by an environmental agent. Later, the altered cell grows and divides to become a population of cells, also called a tumor. 4.2 Control of the Cell Cycle Proto-oncogenes and Tumor Suppressor Genes 4.2 Control of the Cell Cycle Proto-oncogenes and Tumor Suppressor Genes 4.2 Control of the Cell Cycle Proto-oncogenes and Tumor Suppressor Genes When proto-oncogenes mutate (Fig. 5.4), they become cancer-causing genes, called oncogenes. For example, the protein product of the RAS proto-oncogene is part of a signal transduction pathway, one of a series of relay proteins (see Fig. 5.3b). When a signaling molecule, such as a growth factor, binds to a receptor on the cell surface, the Ras protein is activated. Activated Ras protein conveys a message to the nucleus, resulting in gene expression that brings about cell division. If the RAS proto-oncogene is mutated to become an oncogene in such a way that the Ras protein is always activated, no growth factor needs to bind to the cell for the altered Ras protein to send the signal to divide. An altered Ras protein is found in approximately 25% of all tumors 4.2 Control of the Cell Cycle Proto-oncogenes and Tumor Suppressor Genes When tumor suppressor genes mutate, their products no longer inhibit the cell cycle (Fig. 5.5). p53 and BRCA1 are both examples of tumor suppressor genes. The p53 protein is such an important protein for regulating the cell cycle that almost half of all human cancers have a mutation in the p53 gene. Mutations in BRCA1 are often associated with breast and ovarian cancer. The Bioethical feature, “Genetic Testing for Cancer Genes,” discusses some of the challenges facing testing for these genes. 4.3 Mitosis: Maintaining the Chromosome Number Eukaryotic chromosomes are composed of chromatin, a combination of both DNA and protein. Some of these proteins are concerned with DNA and RNA synthesis, but a large proportion, termed histones, have an important role in chromosome structure. On average, a human cell contains at least 2 m of DNA. Yet all of this DNA is packed into a nucleus that is about 5 μm in diameter. The histones are responsible for packaging the DNA so that it can fit into such a small space. When a eukaryotic cell is not undergoing division, the chromatin is dispersed or extended. This makes the DNA available for gene expression. At the time of cell division, chromatin coils, loops, and condenses into a highly compacted form. 4.3 Mitosis: Maintaining the Chromosome Number Each species has a characteristic chromosome number. For instance, human cells contain 46 chromosomes, corn has 20 chromosomes, and the crayfish has 200! This number is called the diploid (2n) number because it contains two (a pair) of each type of chromosome. Humans have 23 pairs of chromosomes. One member of each pair originates from the mother, and the other member originates from the father. Half the diploid number, called the haploid (n) number of chromosomes, contains only one of each kind of chromosome. In the life cycle of humans, only sperm and eggs have the haploid number of chromosomes. Mitosis: The Amazing Cell Process that Uses Division to Multiply! (Updated) Updated Mitosis Video. The Amoeba Sisters walk you through the reason for mitosis with mnemonics for prophase, metaphase, anaphase, and telophase. Expand details to see table of contents. 👇 Video handout here: http://www.amoebasisters.com/handouts Table of Contents: 00:00 Intro 0:44 Why is Mitosis Important? 2:00 Why Don't You Want Cells Dividing all the Time? 2:23 Interphase (occurs before mitosis) 2:55 DNA and Chromosomes 4:07 Chromosome Replication 5:30 PMAT Mitosis Stages 7:30 Cytokinesis (actual splitting of cell) We appreciate the feedback we get for what we need to clarify or should have added. Please see our pinned comment! The Amoeba Sisters videos demystify science with humor and relevance. The videos center on Pinky's certification and experience in teaching biology at the high school level. For more information about The Amoeba Sisters, visit: http://www.amoebasisters.com/about-us.html REFERENCE: We cover the basics in biology concepts at the secondary level. If you are looking to discover more about biology and go into depth beyond these basics, our recommended reference is the FREE, peer reviewed, open source OpenStax biology textbook: https://openstax.org/details/books/biology -------------------------------------------------------------------- Support Us? https://www.amoebasisters.com/support-us Our Resources: Biology Playlist: https://www.youtube.com/playlist?list=PLwL0Myd7Dk1F0iQPGrjehze3eDpco1eVz GIFs: https://www.amoebasisters.com/gifs.html Handouts: https://www.amoebasisters.com/handouts.html Comics: https://www.amoebasisters.com/parameciumparlorcomics Unlectured Series: https://www.amoebasisters.com/unlectured Connect with us! Website: http://www.AmoebaSisters.com Twitter: http://www.twitter.com/AmoebaSisters Facebook: http://www.facebook.com/AmoebaSisters Tumblr: http://www.amoebasisters.tumblr.com Pinterest: http://www.pinterest.com/AmoebaSister-s Instagram: https://www.instagram.com/amoebasistersofficial/ Visit our Redbubble store at https://www.amoebasisters.com/store TIPS FOR VIEWING EDU YOUTUBE VIDEOS: Want to learn tips for viewing edu YouTube videos including changing the speed, language, viewing the transcript, etc? https://www.amoebasisters.com/pinkys-ed-tech-favorites/10-youtube-tips-from-an-edu-youtuber-duo MUSIC: Music in this video is listed free to use/no attribution required from the YouTube audio library https://www.youtube.com/audiolibrary/music?feature=blog COMMUNITY: We take pride in our AWESOME community, and we welcome feedback and discussion. However, please remember that this is an education channel. See YouTube's community guidelines and how YouTube handles comments that are reported by the community. We also reserve the right to remove comments. TRANSLATIONS: Thank you so much to our translators! Filipino translation: Norman II While we don't allow dubbing of our videos, we do gladly accept subtitle translations from our community. Some translated subtitles on our videos were translated by the community using YouTube's community-contributed subtitle feature. After the feature was discontinued by YouTube, we have another option for submitting translated subtitles here: https://www.amoebasisters.com/pinkys-ed-tech-favorites/community-contributed-subtitles We want to thank our amazing community for the generosity of their time in continuing to create translated subtitles. If you have a concern about community contributed contributions, please contact us. 4.3 Mitosis: Maintaining the Chromosome Number Overview of Mitosis Mitosis is nuclear division in which the chromosome number stays constant. A 2n nucleus divides to produce daughter nuclei that are also 2n. It would be possible to diagram this as 2n → 2n. Figure 5.6 gives an overview of mitosis; for simplicity, only four chromosomes are depicted. Before nuclear division takes place, DNA replication occurs, duplicating the chromosomes. Each replicated chromosome is composed of two sister chromatids held together in a region called the centromere. Sister chromatids are genetically identical—they contain the same DNA sequences. At the completion of mitosis, each of the chromosomes in the daughter cells consist of a single chromatid, sometimes referred to as a daughter chromosome. Mitosis Mitosis in animal cells 4.3 Mitosis: Maintaining the Chromosome Number Mitosis in Animal Cells Mitosis is a continuous process that is arbitrarily divided into several phases for convenience of description: prophase, prometaphase, metaphase, anaphase, and telophase (Fig. 5.7)., Prophase -It is apparent during early prophase that cell division is about to occur. The centrosomes begin moving away from each other toward opposite ends of the nucleus. Spindle fibers appear between the separating centrosomes as the nuclear envelope begins to fragment, and the nucleolus begins to disappear. The chromatin condenses and the chromosomes are now visible. Each is duplicated and composed of sister chromatids held together at a centromere. The spindle begins forming during late prophase. 4.3 Mitosis: Maintaining the Chromosome Number Mitosis in Animal Cells Prometaphase - During prometaphase, preparations for sister chromatid separation are evident. Kinetochores appear on each side of the centromere, and these attach sister chromatids to the kinetochore spindle fibers. These fibers extend from the poles to the chromosomes, which will soon be located at the center of the spindle The kinetochore fibers attach the sister chromatids to opposite poles of the spindle, and the chromosomes are pulled first toward one pole and then toward the other before the chromosomes come into alignment. Notice that even though the chromosomes are attached to the spindle fibers in prometaphase, they are still not in alignment. 4.3 Mitosis: Maintaining the Chromosome Number Mitosis in Animal Cells Metaphase - By the time of metaphase, the fully formed spindle consists of poles, asters, and fibers. The metaphase plate is a plane perpendicular to the axis of the spindle and equidistant from the poles. The chromosomes attached to centromeric spindle fibers line up at the metaphase plate during metaphase. Polar spindle fibers reach beyond the metaphase plate and overlap. Anaphase - At the beginning of anaphase, the centromeres uniting the sister chromatids divide. Then the sister chromatids separate, becoming daughter chromosomes that move toward the opposite poles of the spindle. Daughter chromosomes have a centromere and a single chromatid. What accounts for the movement of the daughter chromosomes? First, the kinetochore spindle fibers shorten, pulling the daughter chromosomes toward the poles. Second, the polar spindle fibers push the poles apart as they lengthen and slide past one another. 4.3 Mitosis: Maintaining the Chromosome Number Mitosis in Animal Cells Telophase During telophase, the spindle disappears, and nuclear envelope components reassemble around the daughter chromosomes. Each daughter nucleus contains the same number and kinds of chromosomes as the original parental cell. Remnants of the polar spindle fibers are still visible between the two nuclei. The chromosomes become more diffuse once again, and a nucleolus appears in each daughter nucleus. Cytokinesis is under way, and soon there will be two individual daughter cells, each with a nucleus that contains the diploid number of chromosomes. Mitosis in plant cells 4.3 Mitosis: Maintaining the Chromosome Number Mitosis in Plant Cells As with animal cells, mitosis in plant cells permits growth and repair. A particular plant tissue called meristematic tissue retains the ability to divide throughout the life of a plant. Meristematic tissue is found at the root tip and also at the shoot tip of stems. Lateral meristematic tissue accounts for the ability of trees to increase their girth each growing season Figure 5.7 also illustrates mitosis in plant cells. Exactly the same phases occur in plant cells as in animal cells. Although plant cells have a centrosome and spindle, there are no centrioles or asters during cell division. The spindle still brings about the distribution of the chromosomes to each daughter cell. 4.3 Mitosis: Maintaining the Chromosome Number Cytokinesis in Animal and Plant Cells Cytokinesis, or cytoplasmic cleavage, usually accompanies mitosis, but they are separate processes. Division of the cytoplasm begins in anaphase and continues in telophase but does not reach completion until just before the next interphase. By that time, the newly forming cells have received a share of the cytoplasmic organelles that duplicated during the previous interphase. Cytokinesis in Animal Cells As anaphase draws to a close in animal cells, a cleavage furrow, which is an indentation of the membrane between the two daughter nuclei, begins to form. The cleavage furrow deepens when a band of actin filaments, called the contractile ring, slowly forms a constriction between the two daughter cells. The action of the contractile ring can be likened to pulling a drawstring ever tighter about the middle of a balloon, causing the balloon to constrict in the middle. Meiosis (Updated) Updated meiosis video. Join the Amoeba Sisters as they explore the meiosis stages with vocabulary including chromosomes, centromeres, centrioles, spindle fibers, and crossing over. Expand details to see table of contents 👇 This video also compares meiosis with mitosis. This video has a handout here: http://www.amoebasisters.com/handouts.html Major Points in Table of Contents: Intro 00:00 Mitosis vs. Meiosis Comparison 0:17 Gametes and Chromosome Count Compared to Body Cells 0:46 Interphase 1:44 Meiosis I 3:36 Crossing Over (in Prophase I) 3:56 Meiosis II 5:25 End Result of Meiosis 6:17 The Amoeba Sisters videos demystify science with humor and relevance. The videos center on Pinky's certification and experience in teaching biology at the high school level. For more information about The Amoeba Sisters, visit: http://www.amoebasisters.com/about-us.html We cover the basics in biology concepts at the secondary level. If you are looking to discover more about biology and go into depth beyond these basics, our recommended reference is the FREE, peer reviewed, open source OpenStax biology textbook: https://openstax.org/details/books/biology Support Us? https://www.amoebasisters.com/support-us Our Resources: Biology Playlist: https://www.youtube.com/playlist?list=PLwL0Myd7Dk1F0iQPGrjehze3eDpco1eVz GIFs: https://www.amoebasisters.com/gifs.html Handouts: https://www.amoebasisters.com/handouts.html Comics: https://www.amoebasisters.com/parameciumparlorcomics Unlectured Series: https://www.amoebasisters.com/unlectured Connect with us! Website: http://www.AmoebaSisters.com Twitter: http://www.twitter.com/AmoebaSisters Facebook: http://www.facebook.com/AmoebaSisters Tumblr: http://www.amoebasisters.tumblr.com Pinterest: http://www.pinterest.com/AmoebaSister-s Instagram: https://www.instagram.com/amoebasistersofficial/ Visit our Redbubble store at https://www.amoebasisters.com/store TIPS FOR VIEWING EDU YOUTUBE VIDEOS: Want to learn tips for viewing edu YouTube videos including changing the speed, language, viewing the transcript, etc? https://www.amoebasisters.com/pinkys-ed-tech-favorites/10-youtube-tips-from-an-edu-youtuber-duo MUSIC: Music in this video is listed free to use/no attribution required from the YouTube audio library https://www.youtube.com/audiolibrary/music?feature=blog COMMUNITY: We take pride in our AWESOME community, and we welcome feedback and discussion. However, please remember that this is an education channel. See YouTube's community guidelines and how YouTube handles comments that are reported by the community. We also reserve the right to remove comments. TRANSLATIONS: While we don't allow dubbing of our videos, we do gladly accept subtitle translations from our community. Some translated subtitles on our videos were translated by the community using YouTube's community-contributed subtitle feature. After the feature was discontinued by YouTube, we have another option for submitting translated subtitles here: https://www.amoebasisters.com/pinkys-ed-tech-favorites/community-contributed-subtitles We want to thank our amazing community for the generosity of their time in continuing to create translated subtitles. If you have a concern about community contributed contributions, please contact us. Figure 5.11 Meiosis I in an animal cell. Figure 5.15 Meiosis I compared to mitosis Laws of Heredity ENGR. ARIEL M. ROSALES DNA, Chromosomes, Genes, and Traits: An Intro to Heredity Explore DNA structure/function, chromosomes, genes, and traits and how this relates to heredity! Video can replace old DNA structure function video and in addition covers foundational concepts of heredity. Expand details for video handout: http://www.amoebasisters.com/handouts and table of contents. Table of Contents: Video Intro 00:00 Intro to Heredity 1:34 What is a trait? 2:08 Traits can be influenced by environment 2:15 DNA Structure 3:25 Genes 5:32 Some examples of proteins that genes code for 5:54 Chromosomes 6:37 Recap 7:18 To learn more about heredity including dominant and recessive traits, alleles, and probabilities in inheritance, see our full playlist here: https://www.youtube.com/watch?v=fcGDUcGjcyklist=PLwL0Myd7Dk1FVxYPO_bVbk8oOD5EZ2o5W The Amoeba Sisters videos demystify science with humor and relevance. The videos center on Pinky's certification and experience in teaching biology at the high school level. For more information about The Amoeba Sisters, visit: http://www.amoebasisters.com/about-us.html We cover the basics in biology concepts at the secondary level. If you are looking to discover more about biology and go into depth beyond these basics, our recommended reference is the FREE, peer reviewed, open source OpenStax biology textbook: https://openstax.org/details/books/biology Support Us? https://www.amoebasisters.com/support-us Our Resources: Biology Playlist: https://www.youtube.com/playlist?list=PLwL0Myd7Dk1F0iQPGrjehze3eDpco1eVz GIFs: https://www.amoebasisters.com/gifs.html Handouts: https://www.amoebasisters.com/handouts.html Comics: https://www.amoebasisters.com/parameciumparlorcomics Unlectured Series: https://www.amoebasisters.com/unlectured Connect with us! Website: https://www.AmoebaSisters.com Twitter: http://www.twitter.com/AmoebaSisters Facebook: http://www.facebook.com/AmoebaSisters Tumblr: http://www.amoebasisters.tumblr.com Pinterest: http://www.pinterest.com/AmoebaSister-s Instagram: https://www.instagram.com/amoebasistersofficial/ Visit our Redbubble store at https://www.amoebasisters.com/store TIPS FOR VIEWING EDU YOUTUBE VIDEOS: Want to learn tips for viewing edu YouTube videos including changing the speed, language, viewing the transcript, etc? https://www.amoebasisters.com/pinkys-ed-tech-favorites/10-youtube-tips-from-an-edu-youtuber-duo MUSIC: Music in this video is listed free to use/no attribution required from the YouTube audio library https://www.youtube.com/audiolibrary/music?feature=blog COMMUNITY: We take pride in our AWESOME community, and we welcome feedback and discussion. However, please remember that this is an education channel. See YouTube's community guidelines and how YouTube handles comments that are reported by the community. We also reserve the right to remove comments. TRANSLATIONS: While we don't allow dubbing of our videos, we do gladly accept subtitle translations from our community. Some translated subtitles on our videos were translated by the community using YouTube's community-contributed subtitle feature. After the feature was discontinued by YouTube, we have another option for submitting translated subtitles here: https://www.amoebasisters.com/pinkys-ed-tech-favorites/community-contributed-subtitles We want to thank our amazing community for the generosity of their time in continuing to create translated subtitles. If you have a concern about community contributed contributions, please contact us. Laws of heredity formulated by Gregor Mendel: Law of Segregation: Each organism carries two alleles for each trait, which segregate during gamete formation. Law of Independent Assortment: Alleles for different traits segregate independently of one another during gamete formation. Genetics Combination of traits Patterns of Gene Inheritance Variations Mendel’s Laws “The Investigations of Gregor Mendel.” Principles of inheritance the pea plant homologous chromosomes dominant over recessive Alleles and Genes Join the Amoeba Sisters as they discuss the terms "gene" and "allele" in context of a gene involved in PTC (phenylthiocarbamide) taste sensitivity. Note: as mentioned throughout video, the ability to taste PTC may be more complex than a single gene trait. This video serves as an introduction before exploring Punnett squares in our heredity series: https://www.youtube.com/watch?v=fcGDUcGjcyklist=PLwL0Myd7Dk1FVxYPO_bVbk8oOD5EZ2o5W This video has a handout! http://www.amoebasisters.com/handouts While this video only focuses on basic understanding of alleles and genes as well as the ability to taste- or not taste- PTC (phenylthiocarbamide), we encourage learning more! Here is a recommended reading that expands on the genetics involved in tasting PTC and includes some of the history in how it was discovered: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349222/ The Amoeba Sisters videos demystify science with humor and relevance. The videos center on Pinky's certification and experience in teaching biology at the high school level. For more information about The Amoeba Sisters, visit: http://www.amoebasisters.com/about-us.html We cover the basics in biology concepts at the secondary level. If you are looking to discover more about biology and go into depth beyond these basics, our recommended reference is the FREE, peer reviewed, open source OpenStax biology textbook: https://openstax.org/details/books/biology Support Us? https://www.amoebasisters.com/support-us Our Resources: Biology Playlist: https://www.youtube.com/playlist?list=PLwL0Myd7Dk1F0iQPGrjehze3eDpco1eVz GIFs: https://www.amoebasisters.com/gifs.html Handouts: https://www.amoebasisters.com/handouts.html Comics: https://www.amoebasisters.com/parameciumparlorcomics Unlectured Series: https://www.amoebasisters.com/unlectured Connect with us! 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See YouTube's community guidelines and how YouTube handles comments that are reported by the community. We also reserve the right to remove comments. TRANSLATIONS: Huge thank you to our translators!! Sean Smith - translated subtitles in Afrikaans Evangelia Andreopoulou - translated subtitles in Greek While we don't allow dubbing of our videos, we do gladly accept subtitle translations from our community. Some translated subtitles on our videos were translated by the community using YouTube's community-contributed subtitle feature. After the feature was discontinued by YouTube, we have another option for submitting translated subtitles here: https://www.amoebasisters.com/pinkys-ed-tech-favorites/community-contributed-subtitles We want to thank our amazing community for the generosity of their time in continuing to create translated subtitles. If you have a concern about community contributed contributions, please contact us. The Inheritance of a Single Trait The phenotype of an organism refers to the individual’s actual appearance. The genotype refers to the alleles the chromosomes carry that are responsible for that trait. Gamete Formation & One-Trait Crosses Independent Assortment Mendel had no knowledge of meiosis, but he could see that his results were attainable only if the sperm and eggs contain every possible combination of factors. This caused him to formulate his second law of inheritance, also called the law of independent assortment. The law of independent assortment states the following: Each pair of factors separates independently, without regard to how the others separate. All possible combinations of factors can occur in the gametes. The Inheritance of Two Traits Homologous pairs of chromosomes during meiosis. A cell has two pairs of homologous chromosomes (homologues), recognized by length, not color. The long pair of homologues carries alleles for freckles and the short pair of homologues carries alleles for finger length. The homologues, and the alleles they carry, align independently during meiosis. Therefore, all possible combinations of chromosomes and alleles occur in the gametes, as shown in the last row of cells. The Inheritance of Two Traits Figure illustrates the law of segregation and the law of independent assortment. Because it does not matter which homologue of a pair faces which spindle pole, a daughter cell can receive either homologue and either allele. A Punnett square represents all possible sperm fertilizing all possible eggs, so following are the expected phenotypic results for a dihybrid cross: 9 freckles and short fingers, 3 freckles and long fingers, 3 no freckles and short fingers, 1 no freckles and long fingers. Dihybrid cross. Each dihybrid can form four possible types of gametes, so four different phenotypes occur among the offspring in the proportions shown. In the two-trait cross depicted in Figure 23.7, a person homozygous for freckles and short fingers (FFSS) reproduces with one who has no freckles and long fingers (ffss). The law of segregation gametes for the ffss parent have to be fs. Therefore, their offspring will all have the genotype FfSs and the same phenotype (freckles with short fingers). This genotype is called a dihybrid because the individual is heterozygous in two regards: presence of freckles and finger length. Dihybrid cross. Each dihybrid can form four possible types of gametes, so four different phenotypes occur among the offspring in the proportions shown. When the dihybrid FfSs reproduces with another dihybrid that is FfSs, what gametes are possible? The law of segregation tells us that each gamete can have only one letter of each kind, and the law of independent assortment tells us that all combinations are possible. Therefore, these are the gametes for both dihybrids: FS, Fs, fS, and fs. A Punnett square represents all possible sperm fertilizing all possible eggs, so following are the expected phenotypic results for a dihybrid cross: 9 freckles and short fingers 3 freckles and long fingers 3 no freckles and short fingers 1 no freckles and long fingers This 9:3:3:1 phenotypic ratio is always expected for a dihybrid cross when simple dominance is present. We can use this expected ratio to predict the chances of each child receiving a certain phenotype. For example, the chance of getting the two dominant phenotypes together is 9 out of 16, and the chance of getting the two recessive phenotypes together is 1 out of 16. SUMMARY Law of Segregation: According to this law, each organism carries two alleles (alternative forms of a gene) for each trait, with one allele inherited from each parent. During gamete formation, these alleles segregate or separate, so that each gamete carries only one allele for a particular trait. During fertilization, when gametes combine, the offspring inherit one allele from each parent, thus receiving a pair of alleles. Law of Independent Assortment: This law states that alleles for different traits segregate independently of one another during gamete formation. In other words, the inheritance of one trait does not influence the inheritance of another trait. The random alignment and separation of homologous chromosomes during meiosis result in various combinations of alleles in the gametes. SUMMARY Together, these laws explain the observed inheritance patterns and the concepts of dominant and recessive alleles: Dominant Allele: A dominant allele is expressed when present in the genotype, even if only one copy is inherited. Dominant alleles are represented by uppercase letters. For example, if an organism carries a dominant allele for a specific trait (e.g., "B"), it will exhibit the corresponding dominant phenotype (observable trait). Recessive Allele: A recessive allele is only expressed when two copies are inherited (one from each parent). Recessive alleles are represented by lowercase letters. If an organism carries two recessive alleles for a trait (e.g., "bb"), it will exhibit the recessive phenotype. SUMMARY Homozygous: When an organism carries two identical alleles for a particular trait (e.g., "BB" or "bb"), it is said to be homozygous for that trait. Heterozygous: When an organism carries two different alleles for a particular trait (e.g., "Bb"), it is said to be heterozygous for that trait. Genotype: The genetic makeup of an organism, represented by the combination of alleles it carries (e.g., "BB," "Bb," or "bb"). Phenotype: The observable traits of an organism, resulting from the interaction between its genotype and the environment. SUMMARY By understanding these laws and concepts, we can predict the probability of certain traits being expressed in offspring and explain how traits are passed from parents to offspring in a predictable manner. END REFERENCE: R1: Chapter 23 Central Dogma of Molecular Biology ENGR. ARIEL M. ROSALES Genetics - Central Dogma of Life - Lesson 17 | Don't Memorise The Central Dogma of life is very crucial for the functioning of every Cell in our body. The synthesis of Proteins depends upon the code present on DNA. But how exactly is this done? There are two important steps! Watch this video to get introduced to the extremely important processes which are the important parts of the Central Dogma of life. To access all videos related to Genetics, enrol in our full course now: https://bit.ly/GeneticsBasics_DM In this video, we will learn: 0:00 Introduction 0:44 What is the central dogma? 1:23 What is transcription? 2:42 Why is transcription needed? 3:47 What is translation? 6:22 Why is the directionality needed? 6:53 Gene expression 8:53 Eukaryotes prokaryotes To watch more Genetics videos, click here: https://bit.ly/GeneticsBasics_DMYT Don’t Memorise brings learning to life through its captivating educational videos. To Know More, visit https://DontMemorise.com New videos every week. To stay updated, subscribe to our YouTube channel : http://bit.ly/DontMemoriseYouTube Register on our website to gain access to all videos and quizzes: http://bit.ly/DontMemoriseRegister Join us on Facebook: http://bit.ly/DontMemoriseFacebook Follow us on Twitter: https://twitter.com/dontmemorise Follow us : http://bit.ly/DontMemoriseBlog #Genetics #CentralDogma #DNAreplication Transcription makes an RNA copy of DNA The process of transcription produces an RNA copy of the information in DNA. That is, transcription is the DNA-directed synthesis of RNA by the enzyme RNA polymerase. Because DNA is double-stranded and RNA is single-stranded, only one of the two DNA strands needs to be copied. We call the strand that is copied the template strand. The RNA transcript’s sequence is complementary to the template strand. The strand of DNA not used as a template is called the coding strand. It has the same sequence as the RNA transcript, except that U (uracil) in the RNA is T (thymine) in the DNA-coding strand. The RNA transcript used to direct the synthesis of polypeptides is termed messenger RNA (mRNA). Its name reflects its use by the cell to carry the DNA message to the ribosome for processing. Translation uses information in RNA to synthesize proteins The process of translation is by necessity much more complex than transcription. In this case, RNA cannot be used as a direct template for a protein because there is no complementarity—that is, a sequence of amino acids cannot be aligned to an RNA template based on any kind of “chemical fit.” Molecular geneticists suggested that some kind of adapter molecule must exist that can interact with both RNA and amino acids, and transfer RNA (tRNA) was found to fill this role. This need for an intermediary adds a level of complexity to the process that is not seen in either DNA replication or transcription of RNA. Translation takes place on the ribosome, the cellular protein-synthesis machinery, and it requires the participation of multiple kinds of RNA and many proteins. RNA has multiple roles in gene expression Messenger RNA. Even before the details of gene expression were unraveled, geneticists recognized that there must be an intermediate form of the information in DNA that can be transported out of the eukaryotic nucleus to the cytoplasm for ribosomal processing. This hypothesis was called the “messenger hypothesis,” and we retain this language in the name messenger RNA (mRNA). Ribosomal RNA. The class of RNA found in ribosomes is called ribosomal RNA (rRNA). There are multiple forms of rRNA, and rRNA is found in both ribosomal subunits. This rRNA is critical to the function of the ribosome. RNA has multiple roles in gene expression Transfer RNA. The intermediary adapter molecule between mRNA and amino acids is transfer RNA (tRNA). Transfer RNA molecules have amino acids covalently attached to one end and an anticodon that can base-pair with an mRNA codon at the other. The tRNAs act to interpret information in mRNA and to help position the amino acids on the ribosome. Small nuclear RNA. Small nuclear RNAs (snRNAs) are part of the machinery that is involved in nuclear processing of eukaryotic “pre-mRNA.” RNA has multiple roles in gene expression SRP RNA. In eukaryotes, where some proteins are synthesized by ribosomes on the rough endoplasmic reticulum (RER), this process is mediated by the signal recognition particle, or SRP. The SRP contains both RNA and proteins. Small RNAs. This class of RNA includes both micro-RNA (miRNA) and small interfering RNA (siRNA). DNA (deoxyribonucleic acid) DNA Characteristics: able to store information that pertains to the development, structure, and metabolic activities of the cell or organism. stable so that it can be replicated with high accuracy during cell division and be transmitted from generation to generation The Nature of the Genetic Material Frederick Griffith, a bacteriologist, was attempting to develop a vaccine against a form of bacteria (Streptococcus pneumoniae) that causes pneumonia in mammals Alfred Hershey and Martha Chase - used a virus called a T phage, composed of radioactively labeled DNA and capsid coat proteins, to infect Escherichia coli bacteria DNA Structure James Watson and Francis Crick - determined the structure of DNA in the early 1950s DNA is a chain of nucleotides. Each nucleotide is a complex of three subunits—phosphoric acid (phosphate), a pentose sugar (deoxyribose), and a nitrogen-containing base. There are four possible bases: two are purines with a double ring, and two are pyrimidines with a single ring. Adenine (A) and guanine (G) are purines; thymine (T) and cytosine (C) are pyrimidines. DNA Replication – the process of copying one DNA double helix into two identical double helices At the molecular level, several enzymes and proteins participate in the synthesis of the new DNA strands. This process is summarized in Figure 25.5: 1. The enzyme DNA helicase unwinds and “unzips” the double-stranded DNA by breaking the weak hydrogen bonds between the paired bases. 2. New complementary DNA nucleotides fit into place by the process of complementary base pairing. These are positioned and joined by the enzyme DNA polymerase. The DNA polymerase uses each original strand as a template for the formation of a complementary new strand. (cont.) 3. Because the strands of DNA are oriented in an antiparallel configuration, and the DNA polymerase may add new nucleotides only to one end of the chain, DNA synthesis occurs in opposite directions. The leading strand follows the helicase enzyme, while synthesis on the lagging strand results in the formation of short segments of DNA called Okazaki fragments. 4. To complete replication, the enzyme DNA ligase connects the Okazaki fragments and seals any breaks in the sugar-phosphate backbone. 5. The two double helix molecules are identical to each other and to the original DNA molecule. Gene Expression - the process of using the information within a gene to synthesize a protein - relies on the participation of several different forms of RNA (ribonucleic acid) molecules Gene expression requires two processes: 1. Transcription 2. Translation Gene Expression Processes: 1. Transcription During transcription a segment of the DNA called a gene serves as a template for the production of a RNA molecule. 2. Translation During translation gene expression leads to protein synthesis. Translation occurs at the ribosome and requires several enzymes, and several different types of RNA molecules, including mRNA, tRNA, and rRNA. A Mutation, which may arise during replication and/or recombination, is a permanent change in the nucleotide sequence of DNA. Mutation Damaged DNA can be mutated either by substitution, deletion or insertion of base pairs. Mutations, for the most part, are harmless except when they lead to cell death or tumor formation. Mutation The mutation is a process that produces a gene or chromosome that differs from the wild type (arbitrary standard for what “normal” is for an organism). The mutation may result due to changes either on the gene or the chromosome itself. Thus, broadly mutation maybe: 1.Gene mutation where the allele of a gene changes. 2.Chromosome mutation where segments of chromosomes, whole chromosomes, or entire sets of chromosomes change. Types of Mutations There are various schemes for classification of different kind of mutations. Depending on: The Type of Cell Involved Mode of Origin Direction of Mutation Size and Quality Phenotypic Effects Magnitude of Phenotypic Effect Loss of Function or Gain of Function Type of Chromosome Involved Chromosomal Mutation and Types References Gene Mutations Mutations are heritable changes in the genetic coding instructions of DNA. They are essential to the study of genetics and are useful in many other biological fields Categories of Mutations 1. Somatic mutations - arise in somatic tissues, which do not produce gametes. These mutations are passed on to other cells through the process of mitosis, which leads to a population of genetically identical cells (a clone). 2. Germ-line mutations - arise in cells that ultimately produce gametes. Size According and Qualityto size following two types of mutations have been recognized: 1. Point mutation 2. Multiple mutations or gross mutations. 1. Point mutation When heritable alterations occur in a very small segment of DNA molecule, i.e., a single nucleotide or nucleotide pair, then this type of mutations are called “point mutations”. The point mutations may occur due to following types of subnucleotide change in the DNA and RNA. – Deletion mutations. The point mutation which is caused due to loss or deletion of some portion (single nucleotide pair) in a triplet codon of a cistron or gene is called deletion mutation. – Insertion or addition mutation. The point mutations which occur due to addition of one or more extra nucleotides to a gene or cistron are called insertion mutations. The mutations which arise from the insertion or deletion of individual nucleotides and cause the rest of the message downstream of the mutation to be read out of phase, are called frameshift mutations. – Substitution mutation. A point mutation in which a nucleotide of a triplet is replaced by another nucleotide, is called substitution mutation. Figure 25.20 Point mutations. The effect of a point mutation can vary. Starting at the top: Normal sequence of bases results in a normal sequence of amino acids; next, a base substitution can result in the wrong amino acid; in the final two rows, an addition or deletion can result in a frameshift mutation, altering all the codons downstream of the point mutation. 2. When Multiple mutations changes involving more than one nucleotide pair, oror entiregross gene, then such mutations are called gross mutations. The mutations. gross mutations occur due to rearrangements of genes within the genome. It may be: 1. The rearrangement of genes may occur within a gene. Two mutations within the same functional gene can produce different effects depending on gene whether they occur in the cis or trans position. 2. The rearrangement of gene may occur in number of genes per chromosome. If the numbers of gene replicas are non- equivalent on the homologous chromosomes, they may cause different types of phenotypic effects over the organisms. 3. Due to movement of a gene locus new type of phenotypes may be created, especially when the gene is relocated near heterochromatin. The movement of gene loci may take place due to following method: i. Translocation. Movement of a gene may take place to a non-homologous chromosome, and this is known as translocation. ii. Inversion. The movement of a gene within the same chromosome is called inversion. Type of Chromosome According Involved to the types of chromosomes, the mutations may be of following two kinds: 1.Autosomal mutations. This type of mutation occurs in autosomal chromosomes. 2.Sex chromosomal mutations. This type of mutation occurs in sex chromosomes. Chromosomal Mutation and Types The changes in the genome involving chromosome parts, whole chromosomes, or whole chromosome sets are called chromosome aberrations or chromosome mutations. Chromosome mutations have proved to be of great significance in applied biology— agriculture (including horticulture), animal husbandry and medicine. Chromosome mutations are inherited once they occur and are of the following types: a. Structural changes in chromosomes b. Changes in number of chromosomes Structural changes in chromosomes: 1.Changes in number of genes (a) Loss: Deletion which involves loss of a broken part of a chromosome. (b) Addition: Duplication which involves addition of a part of chromosome. 2.Changes in gene arrangement: (a) Rotation of a group of genes 1800 within one chromosome: Inversion in which broken segment reattached to original chromosome in reverse order. (b) Exchange of parts between chromosomes of different pairs: Translocation in which the broken segment becomes attached to a non- homologous chromosome resulting in new linkage relations. A deletion occurs when a single break causes a chromosome to lose an end piece or when two simultaneous breaks lead to the loss of an internal chromosomal segment. When an individual inherits a normal chromosome from one parent and a chromosome with a deletion from the other parent, they no longer have a pair of alleles for each trait, which can result in a syndrome. In a duplication, a chromosomal segment is repeated in the same chromosome or in a nonhomologous chromosome. In any case, the individual has more than two alleles for certain traits. An inverted duplication is known to occur in chromosome 15. Inversion means that a segment joins in the direction opposite from normal. Children with this syndrome, called inv dup 15 syndrome, have poor muscle tone, mental impairment, seizures, a curved spine, and autistic characteristics, including poor speech, hand flapping, and lack of eye contact A translocation is the exchange of chromosomal segments between two nonhomologous chromosomes. If a person has both of the involved chromosomes, they will have the normal amount of genetic material and generally be healthy, unless the chromosome exchange breaks an allele into two pieces. However, if a person inherits only one of the translocated chromosomes, they will have only one copy of certain alleles and three copies of certain other alleles. An inversion occurs when a segment of a chromosome is turned 180 degrees. Although the same genes are present in the inverted segment, the reverse sequence of alleles can lead to altered gene activity. Shape, circle Description automatically generated Types of Gene Mutations a. Base substitutions The simplest type of gene mutation is a base substitution, the alternation of a single nucleotide in the DNA. Base substitutions are of two types. In a transition, a purine is replaced by a different purine or, alternatively, a pyrimidine is replaced by a different pyrimidine. In a transversion, a purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine. Types of Gene Mutations b. Insertions and deletions The second major class of gene mutations contains insertions and deletions—the addition or the removal, respectively, of one or more nucleotide pairs. Insertions and deletions within sequences that encode proteins may lead to frame shift mutations, changes in the reading frame of the gene. Types of Gene Mutations c. Missense mutation A base substitution that alters a codon in the mRNA, resulting in a different amino acid in the protein. d. Nonsense mutation Changes a sense codon (one that specifies an amino acid) into a nonsense codon (one that terminates translation). If a nonsense mutation occurs early in the mRNA sequence, the protein will be greatly shortened and will usually be nonfunctional. e. Silent mutation Alters a codon but the codon still specifies the same amino acid. Repair of DNA Base Excision Repair Base Excision Repair eliminates modified bases like those that have been deaminated, methylated or modified chemically. The bases cytosine, adenine and guanine can undergo spontaneous, depurination to respectively form uracil, hypoxanthine and xanthine. These altered bases do not exist in the normal DNA, and therefore need to be removed. This is carried out by base excision repair. A defective DNA in which cytosine is deaminated to uracil is acted upon by the enzyme uracil DNA glycosylase. Nucleotide Excision Repair Nucleotide excision Repair is ideally suited for a large scale defects in DNA. The process is activated when a bulky lesion has been produced, such as DNA damage due to ultraviolet light, ionizing radiation and other environmental factors, often results in the modification of certain bases, strand breaks, cross linkages etc. Nucleotide Excision Repair After the identification of the defective piece of DNA, the DNA double helix is unwound to expose the damaged part. An excision nuclease (exinuclease) cuts the DNA on either side (upstream and downstream) of the damaged DNA. This defective piece is degraded. The gap created by the nucleotide excision is filled up by the DNA polymerase which gets ligated by DNA ligase. Mismatch Repair Despite high accuracy in replication, defects do occur when the DNA is copied. For instance, cytosine (instead of thymine) could be incorporated opposite to adenine. Mismatch repair corrects a single mismatch base pair e.g. C to A, instead of T to A. The template strand of the DNA exists in a methylated form, while the newly synthesized strand is not methylated. The difference allows the recognition of the new strand. The enzyme GATC endonuclease cuts the strand at adjacent methylated GATC sequence. This is followed by an exonuclease digestion of the defective strand and thus its removal. A new strand is now synthesized to replace the damage one Double-Strand break repair Double-Strand break repair ( DSBs) in DNA are dangerous. They result in genetic recombination which may lead to chromosomal translocation, broken chromosomes, and finally cell death. DSBs can be repaired by homologous recombination or non- homologous end joining. Homologous recombination occurs in yeasts while in mammals, non-homologous and joining dominates. RECOMBINATION References https://thebiologynotes.com/types-of-mutations/ https://www.researchgate.net/publication/340091209_Gene_Mutations https://www.slideshare.net/KamleshYadav35/mutation-repair- recombination https://www.youtube.com/watch?v=mCaFgwWH61o R1: Chapters 24-25

Lecture 4 - Genetics PDF

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