this is a video for d2.2 on gene expression which is a higher level topic now we can think of gene expression as being a process so we inherit alals from our parents that is our genotype the phenotype is the physical expression of those traits so if we go back and think about what a gene is a gene is a segment of DNA that codes for a protein so gene expression needs to involve manufact facturing proteins so we're talking about stages of transcription taking DNA and using that as a template to make mRNA translation translating mRNA into an amino acid sequence and then protein function so genes are segments of DNA that um code for a specific protein promoters are regions in the beginning of a gene so they're actually base sequences um that tell RNA polymerase where transcription should begin transcription factors which I'll do here in blue are binding proteins that can bind to this promoter and can act as either an enhancer or a silencer enhancers are going to promote transcription so those are going to be things that say yes let's Express this Gene silencers are going to be things that inhibit transcription so prevents that Gene from being expressed let's take a look at this section of DNA so we've got a gene a gene is a segment of DNA that codes for a specific protein and we've got the promoter region which is a base sequence to which RNA polymerase would bind so that it knows where transcription should begin Upstream of that Gene okay so before it um we have regions called silencers and enhancers and these are regions where a transcription Factor could potentially bind so transcription factors are proteins that can either inhibit or promote um transcription if a transcription Factor binds to an enhancer then transcription is increased that promotes transcription which means that that Gene is going to be expressed if however the transcription Factor binds to the silencer region that is going to inhibit transcription and this is how sales turn off genes right making sure that that Gene is not expressed by making sure that that protein is not manufactured let's take a look at this mature mRNA that is the product of posttranscriptional modification you have all of your exons that have been spliced together your five Prime cap and a poly a tail I've shown this with only four A's um but the reality is is that this can have a varying number okay now as this mRNA is translated at ribosomes you know one piece of mRNA can be translated many times over this poly a tail tends to degrade and shorten mRNA molecules with short tails are less likely to be translated because they're more more vulnerable to degradation by nucleas enzymes so as this tail gets shorter and shorter this mRNA is less likely to be translated but by controlling the length of the polyat tail to begin with cells can control how much of a protein that is made using that mRNA so if we need to make a large amount of proteins using this one piece of mRNA the cell would add on a very long polyat tail if only a short amount of that Pro or only a small amount of that protein is needed a short tail would be manufactured to begin with hormones can influence the length of this poly a tail also so this is a complex process but there is a link here between the length of the tail and the n a number of times that this mRNA can be translated which is one way that cells can control that protein production now all the cells in your body came from that one original fertilized egg that zygote which made copies of itself and eventually became an embryo a ball of undifferentiated stem cells through the process of cell specialization or cell differentiation those stem cells differentiated into many different cell types well how do they do that because all of these cells have an identical genome cells control cell division or cells control cell specialization by turning on or turning off genes and when we say turning on genes that means that those genes are expressed and turning off genes means that those genes are not expressed they still have those genes they just are not expressed so for example example a liver cell is going to have all of the genes in the entire Human Genome it is going to express the genes that help it perform its jobs and it is going to not express genes that would help other cells do their jobs this process of cell differentiation is known as epigenesis okay so it's the result or it results in different tissues and again this is all related to activating some genes and silencing others so activated is turned on and expressed silence is turned off or not expressed activation and silencing is due to what we call an epigenetic tag epigenetic tag are chemical modifications that cause some Gene to be expressed While others are silenced remember it doesn't affect the gene themselves just whether or not they are expressed and transcribed and translated into proteins and it's really important that we understand the difference between or the relationship between genes and proteins so genomes this is all of the genetic information in a Cell right so all of the base sequences the transcriptome is all of the MRNA sequences that a cell can produce so remember this can be controlled in lots of different ways and production of different mRNA sequences is definitely an option especially when you think about TR posttranscriptional modification the proteome is all of the proteins produced by a cell and you'll notice that this goes up in terms of complexity even from one mRNA sequence we can produce several proteins if you edit out um different amino acid sequences or if you change the tertiary structure there's lots of things that you can do here also it's worth noting that this proteome is going to vary for different individual cells at different times there will be some times when a cell really needs a certain protein and so it will produce it but it might not produce that same protein at other times so the Genome of an organism remains constant but the transcriptome and the proteome are going to vary depending on the needs of the cell at that time now again controlling genes means controlling the production of that protein so one of the examples of epigenetic tagging that we'll look at is something called methylation I love this because it's exactly what it sounds like it's a type of epigenetic tag that involves adding a methyl Group which is ch3 and that methyl group can be added directly to DNA or to histone proteins if that methyl methyl group is added to base sequences on the promoter of a gene it inhibits transcription so it can be added directly to like let's say the cysteine um nucleic acid um that nitrogenous base so if that methyl group is added there again that will silence the gene in UK carot uh DNA is wrapped around those octomer of histone proteins and histone proteins have several important functions one of which is to help control genetic expression you can actually add a methyl group to those histone proteins and that changes the availability of DNA to transcription it kind of squishes the histones together and it hides some of the DNA so that is a way for cells to control genetic expression by again making sure that that protein cannot be produced because you're inhibiting iting the very first process of transcription in addition to inheriting genomes cells that are the product of mitosis also inherit the epig genome which is all of the epigenetic tags in an organism so what does that mean what are the implications well let's say this neuron is looking like a neuron because of its epigenetic tags it is um expressing all of the genes for how to look and function like a neuron and it is silencing all the genes for the functions of the other cells if this neuron undergoes mitosis then the daughter cell not only inherits the entire genome it also inherits the epigenetic tags so it will automatically look like and function like a neuron theme D is all about continuity and change so during mitosis when cells are inheriting both the genome and the epig genome that is a great example of continuity our previous hypothesis was that all of that epigenome was kind of wiped clean and cells that are the products of miosis did not inherit that epigenome they only inherited The genome and therefore was a great example of change our current understanding is that yes most of that epigenomic tagging is wiped clean during meosis but not all of it that some epigenetic tags might remain now it's important to differentiate between genomic changes and epigenetic tagging genomic changes are changes to the base sequence of the DNA those are mutations mutations acquired by parents during their lifetime are not passed to offspring however epigenetic tagging can be passed to offspring so you can actually inherit patterns of genetic expression from your parents it's important to remember that our phenotype um is some kind of combination of our genotype and environmental factors environmental factors can change our phenotype by changing the pattern of genetic expression and there are a lot of ways that that can happen we'll talk about air pollution as an example air pollution decreases DNA methyl methylation now remember methylation is going to silence genes so if you're decreasing the methyl the methylation you are going to enhance transcription because you're removing the things that are inhibiting the transcription to begin with so this means that we'll have more transcription of genes and many of the genes that are um unmethylated by air pollution are coding for immune system proteins so that means we're going to have more of these proteins which can be good in fighting some of the things that um are complicating factors from air pollution but it can also increase rates of asthma rates of heart attack and it can even affect gestation which is the term of pregnancy so there are a lot of effects of these environmental factors um because they interact with our genes now most of the epigenetic tags are going to be removed during meosis so that's when we're producing um our gametes however not all of them a very very small proportion of those epigenetic tags can actually remain and that can have a huge impact on genetic inheritance especially if it is a dominant Al that is silenced by what we call genomic imprinting right the remaining of those epigenetic tags during gamet formation so let's consider this scenario where I have a male who is homozygous dominant for a certain trait and a female who is homozygous recessive when I put this into a pet Square okay and I had the male over here and the female over here it would appear that all of The Offspring should have the dominant phenotype because all of them have at least one or all of them have one dominant Al let's however consider the possibility that one of the father's um Al is silenced by genomic imprinting okay so this is a silencing Factor well that means that this dominant alil is silenced this dominant alil is silenced this dominant alil is silenced that means that these two individuals will not display the dominant phenotype they will have the recessive phenotype they still have the dominant alil but it was silenced in the father and that was passed down into the Offspring via gamet formation so these are things that can disrupt typical patterns of inheritance particularly when it's the dominant Al that um has remnants of that genomic imprinting so let's talk about a really cool example of genomic imprinting um these are lions and female and male lions have different genomic imprinting patterns okay so female lions can actually carry Offspring from multiple males with in the same litter it's very cool so remember no matter whether you're a male or a female a lion or a butterfly it doesn't matter the the goal is to be passing along genes to offspring so any patterns of genomic imprinting are going to be to give your Offspring the best chance to be conceived to be born to grow to adulthood so for the female lion that means that she's going to have genomic imprinting for large litters that means having having a lot of cubs the more Cubs she has the more likely at least one of them will survive to reproductive age males on the other hand have imprinting for large Offspring okay so they want their Cub to be the biggest cub of the litter if the female is carrying a litter from multiple males so that means that his cub would have the option for like out competing the others so they have different patterns of imprinting usually this kind of evens out into having like medium-sized litters with mediumsized Offspring tigers and lions can actually interbreed they don't produce fertile offspring because they're not the same species but they can produce Offspring they can interbreed but female tigers can only carry a litter from a single male at a time so there's a no imprinting in Tigers there's no kind of like competition between other males within the litter so no imprinting exists so when they interbreed you get some really interesting observations due to this imprinting if the male parent is a tiger and the female parent is a lion there's no imprinting from male tigers to be big so that lion cub or sorry this Offspring between them is going to be relatively small there's no Advantage for being big no imprinting for being big if the male parent is a lion and the female parent is a tiger then this imprinting on male lions for having big cubs really comes through and so you get an um an offspring that is often even larger than either parent so it's a really great example here of genomic imprinting before we get into monozygotic twin studies let's just talk about the difference between monozygotic and dizygotic twins monozygotic twins come from one zygote so mono means one so this means that I have one egg fertilized by one sperm and that creates one zygote this zygote under goes mitosis many times to become a ball of undifferentiated cells and then for unexplainable reasons that ball of undifferentiated cells gets separated and each of these undifferentiated balls of cells grows up into its own individual they are identical because they came from the same sperm and egg so these are our identical twins they have identical genomes d means two D zygotic twins come from two separate eggs that are fertilized by two separate sperm so they make two separate zygotes each zygote is going to develop into its own ball of undifferentiated stem cells so here's our embryo and each one of these is going to be its own individual but they are not identical because they came from different sperm and eggs we're going to be focusing on monozygotic Twins and the reason why they are very interesting is because they inherit the same genome and because of that you would think that they would be identical in all ways well remember they have the same genome but they acquire different epigenetic markers throughout their lifetime they're exposed to different environmental factors so it's a really great way to study nature which is the genome part versus nurture which is the epigenetic markers part to see what parts of our physical expression are controlled by genes versus environmental factors so it's a great way to study that so here's a famous set of twins and they are identical twins and one of them was sent to space while the other one one remained on Earth to try to see the effects of space on our physical characteristics so again um a really great way to study this nature versus nurture part you don't have to go to space though to see another great example of environmental factors affecting gene expression let's take a look at one that occurs in our own bodies lactose is a disaccharide um that is found in milk products and it's a great example of a biochemical Factor that can impact gene expression lactase is an enzyme that helps break down lactose into its monosaccharide so the gene for lactase only needs to be expressed while we're eating lactose so when lactose levels rise in our digestive system this repressor protein that normally sits on the silencer part is removed okay so removed or deactivated since that is no longer silenced the gene is expressed lactase that enzyme starts to be produced and this lactose gets broken down into its monosaccharides when the lactose is broken down that means that lactose levels are going to fall and that means we don't need lactase anymore so that Gene will be silenced once again so that we are not producing excess lactase and the last example that we'll talk about here um is a hormone hormones regulate the patterns of genetic expression they can either promote them or they can silence them and estrogen is a great example of a hormonal factor that affects that pattern of genetic expression it does a lot of things one of the things that it can do is it can binded to Target genes and change their expression and we're going to talk particularly about the endometrium if you haven't studied the reproductive chapter yet that's okay the endometrium is this highly vascular lining of the uterus and in order to um develop and maintain that endometrium the cells that are here need to be able to receive uh another hormone called progesterone so what estrogen will do is it will turn on genes in these cells allowing them to produce a protein that acts like a receptor for progesterone those cells start to produce that protein on the outside of their cells they produce receptors for progesterone and then that tissue becomes more responsive to Progesterone so if you get to the chapter or the topic rather on hormones and you're wondering how does one hormone affect the production of another hormone it's usually because the first hormone is um regulating patterns of genetic expression making other target cells more or less susceptible to the second hormone