well first of all nice job on the exam we were quite pleased with how you guys did and so from now on in the course professor Imperiali has been telling you about information flow but information flow within a cell right so information flow from the DNA to the proteins that are made in the cell which determines what that cell does okay and so we're gonna switch directions today and we're going to start talking about how information flows between cells so from parent cell to its daughter cells and we're also going to talk about how information flows from generation to the next okay and this of course is the study of genetics and what genetics is as a discipline is it is the study of genes and their inheritance okay and the genes that you inherit influences what is known as your phenotype and what phenotype is is it simply the set of traits that define you so you can think of it as a set of observable traits okay I mean and this involves your genes as you probably know I mean just this morning I was dropping my son off at school and he was comparing how tall he was compared to his classmates and as he went in he is like thanks for the genes dad so I expect that many of you are gonna be familiar with much of what we'll discuss but we're gonna lay a real solid foundation because it's really fundamental for understanding the rules of inheritance and how that works okay so genetics is a study of genes so what is a gene so there you can think about genes in different ways okay and what we've been talking about up till now we've been talking about molecular biology and what is known as the central dogma and the central dogma states that there's the source of the code is in the DNA and there's an information flow from a piece of DNA which is a gene and a gene is a piece of DNA that then encodes some sort of RNA such as a messenger RNA and many of these RNAs can make specific proteins that do things in your cells in your body okay so that's one very molecular picture of a gene you can think of a gene as a string of nucleotides and there might be a reading frame and those nucleotides that encodes a protein okay so that's a very molecular picture of a gene right the field of genetics started well before we knew about DNA and its importance and what sort of the DNA encoded RNA which encoded proteins okay so the concept of a gene is much older than that and so what you can think of a G another way you can think of a gene is it's essentially the functional unit of heredity okay so it's the functional unit of heredity okay I'll bump this up so I want to just briefly pause and kind of give you an overview of why I think genetics is so important so what you saw up here is you saw a cell divide and I showed you this in the last lecture you saw the chromosomes which are here how they're segregated two different daughters and this is basically you're seeing the information flow from the parent cell into the daughter cell okay but we saw this so I'm just gonna skip ahead so why is this so important okay so I'm gonna give you a fairly grandiose view of why genetics is so important and I'm gonna say that we can make a good argument that genetics is responsible for the rise of modern civilization okay so humans as a species began manipulating genes and genetics even before we had under any understanding of what was going on so this is more of an unconscious selection and so 10,000 years ago humans were hunter-gatherers they'd go out and try to find nuts and seeds and hunt animals and that's how we got our food but around 10,000 years ago was the first example of where humans as a species really altered the phenotype of a plant in this case okay so wild wheat and wild barley the seeds develop in a pod and the biology of the wild wheat is such that the pod shatters and the seeds then spread on the ground where they can be where they can then germinate into new plants okay but 10,000 years ago humans decided that it would be more ideal if we had a form of wheat which didn't shatter which is known as non shattering wheat which in which the seeds remain on the plant and that allows it to be easily harvested at the end of the season okay so 10,000 years ago is one of the first examples where humans really genetically altered the phenotype of a plant and they selected for this non shattering wheat which then allowed the rise of Agriculture okay in addition to wheat we also for about four thousand years ago was the rise of domesticated fruit and nuts so here are some almonds if you would like an almond feel free to have some you guys want some almonds nope if you have a nut allergy don't eat them okay great so wild almonds when you chew them there's an enzymatic reaction that results in cyanide forming Rachel just stopped chewing don't worry these these are almonds that are harvested at Trader Joe's so you're safe and so the wild almonds obviously were not we're not compatible for consumption consumption but 4,000 years ago humans again selected for a form of the almond which involved just a single gene which was non bitter and known as a sweet almond which was also not toxic okay so this doesn't just go for foods but also for clothing so humans have selected for cotton with long lint and that served as a basis for clothing and and sort of allowing us to have fabric and I just want to end with a little story about the almond which is part of the archaeological evidence for when almonds were domesticated was when King Tut's tomb was unearthed and they found a pile of almonds next to the tomb because the the Egyptian culture what they did is they buried the dead with food to sustain them in the afterlife okay so that just gives you an idea as how far back sort of the importance of genetics goes if we think about nowadays right now you are always seeing genetics in the news and you also have the opportunity yourself to sort of do your own genetic experiment and so now you guys are undoubtedly aware of all these companies that want you to send them their DNA and they also want you to send them money such that they can give you information about your family tree and also information about your health okay and so this is now a big business but if you but if you don't understand genetics this is not as useful as it could be okay so I'm just curious how many people here have used one of these services and had their DNA genotyped well and do you think that that really changed your view of who you are or was it kind of so you're looking for genetic disorders and you don't have to tell me anything about that yeah so you know I mean my I have not done this but my dad has done it and he will go find his like relatives and bore them with our ancestry okay so so this is one example of how genetics is really in play today right and not everyone knows how this works I've had people at Starbucks in the morning come up to me with their like with their like 23andme profile and asked me to explain stuff because they know who I am this a little awkward so we can also use genetics for forensics and so this is kind of a I I had a lab manager in the lab and he told me that like people were doing this and like like senior homes in Florida which I thought was kind of funny what I find hilarious about this is the mugshot of the dog right that dog looks so guilty right but you can use DNA to you can use DNA to genotype poop you genotype your neighbor's dog you can get evidence that they're the one that's like pooping on your lawn so that's not so serious example but there are more serious examples of where DNA genotyping is really having an effect in our society and this is something I mentioned in the intro lecture just this past spring someone was suspected as being the Golden State killer this is a cold case the kid the killing has happened 40 years ago but the break came from investigators getting DNA from the suspects relatives to implicate this person in this crime okay so they had DNA from the crime and they saw that there are matches to the DNA at the crime to certain people and then they can reconstruct who might be the person in the right place to commit the crime okay so this is I think this is interesting because it also leads to all sorts of privacy issues right who's gonna gain access to sort of your genotype if you submit it to these companies right I mean this is probably a case right argue there's probably a beneficial result in that you can actually figure out if someone's committed a crime but there are other issues in terms of thinking about insurance companies where we might be interested in having our sort of information not publicly available to insurance companies and maybe this is something we can discuss later on in another lecture for today I want to move on and go through really the fundamentals of genetics and what I'm gonna do is I'm gonna start with the answer okay I'm gonna present to you guys today the physical model for how inheritance happens okay so today we're going to go over the physical the physical model of inheritance and this physical model involves cell division which you saw in the last lecture and also in my opening slide it involves cell division and the physical segregation of the chromosomes during cell division so also chromosome segregation okay so these this is how I'm gonna represent chromosomes and I just want to kind of step you through what all what it all means so I kind of have these two arms that are attached to this central circle the circle is meant to represent the centromere so this is the centromere and you'll remember from the last lecture on Monday the centromere is the piece of the chromosome that physically is attached to the microtubules that are gonna pull the chromosomes to separate poles okay so that's that's called the centromere and usually it's denoted like a constriction in the chromosome or a little circle okay these other parts of the chromosome are the arms so that you have the arms of the chromosome now I'm drawing what's known as a metacentric chromosome it's not important that you know that term but it just means that the centromere is in the middle of the chromosome there are other types of chromosomes where the centromere might be at the end okay so there are different types of chromosomes all right now for all of us we have cells that have different numbers of chromosomes okay some of our cells are what is known as haploid and what I mean by haploid is there is a single set of chromosomes now the cells that we have that are haploid are our gametes so there are eggs and our sperm cells okay so these include gametes okay but most of the cells in your body are what is known as diploid and diploid means there's two complete sets of chromosomes okay and you get one set from one parent the other set from the other parent okay so one set from each parent okay and I'll draw the other set like this and what I'll do is I'll just sort of shade in this one this one to denote that it's different okay so these two chromosomes then are what is known as homologous their homologous chromosomes Moll I guess okay and what I mean by them being homologous is that basically these two chromosomes have the same set of genes okay so they have the same genes they're the same genes but they have different variants of those genes okay so different variants of these genes and these variants are referred to as alleles okay so if you have the same gene but they differ slightly in their nucleic acid sequence then they're distinct alleles of those genes so often the way geneticists refer to these different variants or alleles is we use a capital letter in a lowercase letter okay so this chromosome over here might have a gene that's allele capital a and then this homologous chromosome will have the same gene but a different allele which I'll denote lowercase a okay so in this case big a and little a are different alleles of the same gene they might produce a slightly different protein which would result possibly in a different phenotype okay so everyone understand that distinction oh I want to make one point because this came up last semester and was one of those cases where I forgot the part about the head so I we often just have two alleles when we sort of teach genetics but I hope you can see that because a gene is a long sequence of DNA there's a ton of different alleles you can have within a given gene so one nucleotide difference in that gene would result in a different allele okay so we often refer to two alleles but there can be more than two alleles for a given gene okay does everyone see how that manifests itself okay great any questions up till now yes Carmen in the population so Carmen asked well do can I have like five alleles of a gene and that's a great question and so Thank You Carmen for asking that what I'm what I mean is if we consider a population as a whole right you have two alleles of each gene unless it's a gene that somehow like duplicated and so when we're considering the population there can be more than right I mean right I see we have people with hair color is not a monogenic traits are with brown hair right there's more than just like two possible sort of alleles with possible phenotypes okay all right let's go up this alright now I want to start at the beginning where so most of our cells are diploid and the origin of our first diploid cell is from the union of two gametes okay so I'm going to draw two gametes here each is one end and I'm just going to draw one set of chromosomes for this here so we might have a male gamete and a female gamete and what I'm referring to when I say n here n is basically referring to the number of chromosomes number of chromosomes perhaps I am / haploid genome so when you have 1n it means you're haploid because you have only one set of a haploid genome but early in your life you're we're all the result of a fusion between a male and female gametes and so that creates a diploid cell okay so now this diploid zygote so this is referred to as the zygote is diploid and now has a set of homologous chromosomes okay so I'm only drawing one set of homologous chromosomes here so on the board I'm gonna stick to just one so I don't have to draw them all out in the slides I'm I have three okay so each of these represents a chromosome these are different chromosomes different chromosomes are their different color or have a different sort of centromere position and then these down here that are colored are going to be the homologous chromosomes okay you see how I'm representing this okay so once you have the zygote right so you guys are no longer one cell right you guys each are tens of trillions of cells so this zygote had two the zygotes L had to reproduce itself and your cells had to divide so that you grew into an entire multicellular organism just quickly erase that okay so when most of your cells divide and most of your cells are known as somatic cells when cells of your body or your intestine and your skin when they divide they genetically replicate themselves and they're undergoing a type of cell division known as mitosis okay in mitosis in mitosis it's essentially a cloning of a cell or ideally it's the cloning of the cell so you have a diploid cell it has to undergo DNA replication and when a chromosome undergoes DNA replication it will during mitosis look like this okay and these two different sort of arms or strands they're known as sister chromatids okay so that's just another term you should know these are sister chromatids okay and the sister chromatids if DNA replication happened with any without any errors should be exactly the same as each other in terms of nucleotide sequence okay so after DNA replication this cell will essentially have four times the amount the amount of DNA as a haploid cell and it will split into two cells and again they'll both be diploid okay and I'll just point out if we're thinking about our pair of chromosomes here right Egypt this parent cell has both homologs and the daughter cells because they should be genetically identical also have both homologs okay so that's an example with just one chromosome I'll take you through an example with these three chromosomes here well six chromosomes so you have these are homologs these are homologs these are homologs and during mitosis all all of these chromosomes initially are kind of all over the nucleus but during mitosis they will align along the equator of the cell and what is known as the metaphase plate metaphase is just a fancy term for one particular stage in the mitotic cycle so's and then what will happen is the spindle will attach to either one side or the other side of these chromosomes and it will physically segregate them into different cells okay and what I hope you see see here is that this has six chromosomes this has six chromosomes and these two daughter cells are genetically identical to the parent cell okay so this is known as an equation elision because it's totally equal okay and again the daughter cells are both diploid okay so that's mitosis any questions about mitosis okay moving on we're going to talk now about another type of cell and these are your germ cells and these germ cells undergo an alternative form of cell division known as meiosis okay and your germ cells germ cells produce your egg in sperm and so meiosis essentially is producing gametes such as egg and sperm cells okay so what's the final product gonna be how what should be the genomic content of the final product of meiosis it should be one end right who said that sorry yeah exactly right what's your name Jeremy so Jeremy is exactly right right the germ cells in order to reproduce sexually they should be haploid cells right so that they can combine with another haploid to give rise to a diploid okay so the ultimate result that we want is to have cells that are one end but most of our cells to start out with are diploid so there are 2n okay so what's special about meiosis is you're not just going from 2 n to 2 n but you're reducing the genetic content of the cells you're going from 2 n to a 1 end content okay so again meiosis starts with DNA replication but in this case the first division which is meiosis 1 is not equal and it actually segregates the homologs such that you get one cell that has one of the homologs duplicated and another cell that has the other homologue duplicated ok and I'll show this I'll show it right now so this is the same cell now it's undergone DNA replication as you can see each chromosome has two copies but instead of all the chromosomes lining up in the same position of the metaphase plate what you see is that homologous chromosomes pair at the metaphase plate and what happens here is that the homologous chromosomes are separated to different cells and now you have two cells that are not genetically identical okay so because there's it's not equational it's and there's a reduction in the genetic material that's present in the cells this is known as a reduction Allah vision okay so that's meiosis one and that's a reduction old division and then but this is not yet haploid and so I'll just stick another one in here these cells then undergo another round of division which is known as meiosis two and during this meiosis these sister chromatids are separated such that you're left with one chromosome and by drawing at least one chromosome / / gamete okay so each of these then is 1n okay so again you have the chromosomes but this time you you have them aligned like in mitosis they align the sister chromatids are physically separated and now you see this cell is genetically identical to this cell and this cell here is genetically identical to this cell okay so that's meiosis 2 and that's an equation older vision much more like mitosis okay because the product of the division of those two cells each of those is equal okay and the finally the result of meiosis 2 is that you're then left with gametes that have a haploid content of their genome ok I want to end lecture by doing a demonstration let's see so this could either be amazing or it will be a complete disaster so we're totally going to do it so what everyone come up [Music] wait here sure Evelynn when you can leave when you have to go and we'll have a chromosome loss event okay you just have to be a multiple of four if we have extra people they and the people can supervise go oops sorry alright we got here here you go Brett Andrew sorry I hope I'm not hitting anybody what's that yeah that's the didn't see advantage of these all right there you go miles let's see there you go sorry someone take this all right what do we got here got a little chromosome here sorry all right who doesn't have a chromosome everyone in the class has a chromosome all right one of you wanna come in here all right we'll see how constrained we are in terms of space we've never been this ambitious and had this many chromosomes before so I'm excited to see how this works so you each have a swim noodle there are different colors so different colors represent different chromosomes and then you also have swim noodles that have tape on them and these represent different alleles from your other chromosomes so these two chromosomes would be homologs of each other okay does that make sense okay great all right now the metaphase plate will be kind of along the center of the room so let's first reenact mitosis so why don't you guys find your sister chromatid and then sort of a line in the middle of the room here sister or brother chromatid how are we doing do we have enough space there it's a little packed you can see how you know the cell you can imagine how packed it is inside a cell okay everyone found their sister chromatid normally the sister chromatids they replicate and they get held together so there's no finding of sister chromatids but all right great so segregate and we'll see how you guys did all right in the goal is that you guys would be genetically identical saris okay great that looks like one short red one short red that's good they look genetically identical to me alright so that was mitosis now we're gonna do meiosis okay want you guys aligned like like what would happen during meiosis one okay you guys can come back think about who you're gonna pair with oh all right so what were you looking for when you were pairing who were you looking for your prohm is ohm right okay great all right why don't you guys segregate alright so that was my OSIS 1 meiosis one looks successful to me and now we have to undergo meiosis 2 so maybe what we could do is you guys can rotate in the metaphase spindle can be sort of in this orientation yeah yeah well we want to group over there a group over there grow a group here group here and those will be our four gametes all right you guys set all right go okay terrific everyone haploid looks like everyone is haploid which is good right so look let's just take a minute and think about probability here so what was the probability that a gamete would end up with this orange allele on the red chromosome huh maybe is there two right so these two gametes have that allele these two should not right okay great we just had a chromosome loss so that gamete is in trouble but maybe we could get a TA to rescue this chromosome either one of you is fine there you go David all right that was great now let's you know as you're doing this right you kind of get a sense as to how things could get mixed up right and you know you think inside the cell right so I don't I've lost track of how many chromosomes we have one two three four five six right how many chromosomes do we have we are haploid set for us is how many chromosomes 23 exactly right so it'd be even worse for a human cell to get this to go right so why don't you guys line up in the mitosis configuration and we'll consider some things that could go wrong all right who here is good friends with their with their sister or brother chromatid there's anyone very good friends with their sister or brother chromatid yeah someone become good friends and become inseparable okay which with someone volunteer to be inseparable okay great you guys are now inseparable okay now segregate okay great now what happened there what's that yeah that sell stolen okay so now we have to a duplication of that chromosome what's happened over here with this daughter cell it's missing a chromosome right so these are the types of mistakes that can be associated with a cell becoming cancerous right because let's say there was a gene that suppresses growth on that chromosome and it wasn't on that homologue then you might result in genetic sort of mutant or loss of that gene that would result in uncontrolled proliferation also picking up the copies extra copies of genes that promote growth could allow that cell to have a proliferative advantage okay we're gonna this is sort of short foreshadowing what we're going to talk about later but I just want to kind of like plant the seed now okay why don't we go back and do my OSIS okay now anyone see any friends looking across the aisle now all right great you guys are now inseparable why don't you guys segregate except the inseparable ones oh but but your sister chromatids still have to stay attached there you go see great right so just like last time that this is known as a non distinct disjunction event where the chromosomes don't separate when they should okay great now we want you guys do meiosis to all right you can segregate all right now you see these two gametes over here are lacking an entire orange chromosome and these two gametes here have picked up an additional copy of an orange chromosome okay so they're this the two gametes are no longer haploid for the orange chromosome and if one of these gametes were to fused with a haploid gamete that has an orange chromosome then now you have a zygote that has three copies of the orange chromosome which is abnormal okay so if that work froma zome 21 in humans that would result in something that's called trisomy 21 which is Down syndrome okay so you see how mistakes and how Roma's ohms segregate can result in human disease okay well we give give yourselves a hand good job okay you can just throw the pool noodles on the side and I just have one slide to show you where we're going next she said throat yeah can you share those you're asking if there's crossing over yeah there's crossing over yes and that will that will that will get its own entire lecture yes good question okay so just to give you guys a preview of what's up next so in the next lecture we're going to talk about Mendel and Mendel's peas and we'll talk about the laws of inheritance okay and realize Mendel you know this Mendel is way before DNA or what our knowledge of the gene was okay next we'll talk about fruit flies and Thomas Hunt Morgan and seminal work that led to the chromosome model of inheritance and also resulted in the concepts of linkage and also genetic Maps okay we're gonna go well just sort of anchor yourself right the structure of DNA was published in 1953 so these seminal genetic studies up here were done before we knew about DNA so geneticists were studying genes and their behavior well before we knew DNA was what was responsible and then we'll talk about sequencing and the sequencing Rezo revolution will talk about cloning and molecular biology and how one might go from a human disease to a specific gene that causes it and then finally we'll start talking about entire human genome and genome sequences okay so that's just a preview of where we're going so have a great weekend [Music] you