Hey, hey there dudes, what's going on here back in the game, another reaction video and today we're gonna be learning the members of all my girl We're gonna fully go into it. I've done a funny moments video I tried to learn a few of the members. I can remember Vinny and Hyojung and Yua, I didn't say I'm confident on Yua. Am I right? Yep. Okay. I am right Okay, so I got the screen of like the members on this side just with like their names because I was just having a quick Skim through this and I was just seeing what the subtitles would be like, you know If it was showed the full name or if I would like to do the initials and it's got the initials for them So it'd be nice for me to actually learn their names So once I see them talking and stuff I'll quickly look over onto this screen see what their name is and what a pin what a boom what a bam I'm gonna be learning the members and we're gonna be doing it through their series called sketchbook And I am freaking excited for this legit I am freaking excited for learning freaking oh my god, and I need to get back into learning 17 Okay, tomorrow 17 video got to nail the members But anyways today we're learning all my girl and oh my god. I cannot wait so let's get straight into this I'm freaking excited. I hope you guys are too and let's do this. Oh Okay, I'm drawing stuff.   Oh, this looks like they're Pan-Cochin showcases in it. No M. M. M. M. Mimmy. Oh, that's pretty easy to remember Mimmy Oh Also, that would be so sad because it's finished. Why is the first episode said episode? J. E.  Have you dirt? Miracles. Oh, okay. There's been in the back. Yo Benny's pretty Little pretty song song here song haze in the blue. Okay song here. Yeah, Lila is such a good song J. H. J. H. Jeeho Jeeho Jeeho Jeeho Jeeho. Oh Hershey's yo, Hershey's Hershey's a good man Wait, oh, there's Mimi Mimi and so y'all song he song he Are you received the book here?  It will be a miracle for me I think I might do this daddy there's like 30 episodes isn't it? He's exactly 30 episodes I'm gonna do this daddy one month of all my girl. Okay, that was actually pretty good I learned what I can remember one member from this which was a Mimi I can remember Mimi from this so that's good. That's good. We're getting progress. I can't wait for the day We are just like yo Hey, Mimi. Hey Hey, yo, John. Oh, hey, you are. Oh, hey, buddy. I'm just knowing all the names. I cannot wait for that Oh, but I I'm definitely gonna try and do this daddy because it looks like there's only a few minutes long So it shouldn't be that that back. So I'll definitely do this once a day Maybe like the I don't know when I'll just do it once a day. How about that? But uh you guys this is gonna be all of this video I hope you guys did and join in case you didn't have to show some support by leaving a like and also Comment down below All my girl facts because I am learning this group because they are amazing So I love to know some facts about them so comment those down below and also subscribe guys and new to the channel because It's gonna be daily on my girl videos for a while and then I will try and like do stuff After I've reacted to all of this, you know after all the sketchbook I'll try and do some other things to react maybe like more funny moments or something like that I don't know like I'll find videos around. Okay. I'll find them and uh, yeah of them that I hope you guys have a great day and just keep on smiling and adios amigo


So the party starter legendary melee weapon basically give you fire fists these things are both brutal and a hilarious at the same time I mean, I wish I could show you gameplay, but with YouTube penalizing my videos for showing actual gameplay of this game I can't but trust me for the little work it takes to get these they're 100% worth it How's it going guys? My name is DPG and if you do enjoy the video leaving a like really helps out and if you like what you see Be sure to subscribe Now most if not all legendaries in this game at some point or another are tied to you completing the game's main story quest line For sure you can progress probably start this quest, but I ain't certain if you'll be able to finish it So if you can't finish it and you're stuck somewhere it's because you need to progress the main Campaign so keep that in mind So this quest what a quest for this is called a drunken disorderly It's a lost and found side quest mission and it's picked up within the Ocean Avenue area So from the whole tell checkpoint people follow this path I take on screen now to grab this quest. You may have to kill a zombie or two that may be in your way From here you need to head to Venice Beach and to the Roses Tattoo Shop located on screen here Once you are going inside there should be a couple of zombies in here you need to take out Including a screamer so be careful Once taken out pick this item up to progress this quest You now need to come to the gang green shop located here here. You are looking for a zombie called Cold now he can appear around the back of the shop or out front But when you do find him take him out and collect the item he drops You then guys need to head to the peer area and to this point right here Now once you are here, there's an item on the table that you have to collect so quickly grab it Now guys you need to hang about as a named enemy will spawn in who you have to take out His name is Jordan So take this fire spitting pussy out and grab the car keys that he drops Now guys you need to head back to that ocean Avenue hotel and to this point right here I won't see you guys take who I take to the hotel parking lot until a bit of this vehicle open it And you're rewarded these amazing Legendaries and they have it guys enjoy this one guys if you enjoyed the video Living a lot coolly helps out you feel like what you see once you more be sure to subscribe and hopefully guys I will see you on that next one


ion because here one of them gains a new function and changes and here not but then and here they have when you cartoon this you always put up sorry each has one loss of function and that's also what I put in my cartoon earlier here they each have one loss of function right so you always draw it symmetric whereas here it's asymmetric but actually there's no reason for that there's no theory we said it should be asymmetric or symmetric so you can have asymmetry under sub-functionation also so asymmetry although there's been quite a few pays which said it was indicative of neo-functionization that's not necessarily the case so what you need to decide whether it's sub-functionation or neo-functionation is to know what was the outgroup state because a big difference between neo-functionalization and sub-functionalization is that together they describe the function of the outgroup of the sorry of the ancestor or one has the function of the ancestor the other has a new function now we don't have a time machine because the physicists still haven't given us the time machine and if you have any physicists friends you can complain to them but we have our groups which is second best and that we have thanks to comparative genomics and autologues so let's rejoice we should compare our duplicates genes to an outgroup not duplicated and see if one copy is like the outgroup and function and the other is different this looks like neo-functionalization if the two paralogs are a bit different and together they describe the function of the outgroup that looks like sub-functionalization and I don't have a result of mine on this because I've been trying to test this for years and every time I try to start testing it the new results on the autologue conjecture and I go back to that so it's still my plans for next year but it's been my plan for next year for six seven years but other people have worked on it in the meantime so here for example you have RNA-seq human mouse where they looked at the expression of the duplicates which are human specific or mouse specific comparing to the outgroup and the other species and for example here sorry here they don't have an outgroup sorry my bad so you cannot tell so this is an example of asymmetry here you have these two genes have different expression see this gene is expressed highly in the lung the kidney the liver and the testis and the paralogue is also expressed in the testis but highly in the heart where this one wasn't highly in the cortex where this one wasn't and here I have a gene which has highly expressed in one copy and lowly in the other and actually this is quite frequent it's never in our mothers but it's quite common so this kind of study is interesting but don't really allow us to choose so we need outgroups and this is where the fish genome duplication are very interesting because in fishes we have not only genome duplications which means a lot of genes which are duplicate with the same age so we can compare them but we also have outgroups for one thing a nice outgroup to all fishes is human and mouse where we have a lot of data so when I work on fishes I treat human and mouse as the outgroup which is very convenient because there is a lot of data and we also have extra genome duplication salmonids and salmonids have an outgroup all the other fish for which we have data notably zebrafish and I wish I could tell you I'm going to give you the final answer here but it's not the case so this figure is a bit complicated but what's important is that here if you compare so here what they did they sequenced the gar and the gar if you go back here is a fish which is which diverged by speciation from other fishes before the teleost genome duplication so it's an outgroup to the teleost genome duplication so all the genes are duplicated in all teleost fishes from the genome duplication a single copy in the gar and so they did the genome and the transcriptome of the gar and compared expression and so we have genes like this where you have the gar in gray and one paralogue in zebrafish which is expressed in the same place as the so one paralogue here in red is expressed in the same place as the outgroup the gar and the other paralogue in blue is expressed a different place so that looks like neo-functionization and you can do the same thing when you have the medica so it allows you a biological replicate the different fish also teleost and they have the same pattern but you also have patterns like this where the gar gene is expressed in the brain and the heart and one copy in the of the gene duplication the onologue in zebrafish expressed in the brain and the other in the heart so this really looks like sub-functionization and when they counted the two types they had much more sub-functionizations than neo-functionizations they also verified this by correlating the levels of expression so the here for example you see that the here you have the one copy of the in the zebrafish is lowly correlated to the gar outgroup the other copy is also lowly correlated to the gar outgroup but if i sum their expression so and sub-functional sub-functionalization i'm going to assume that the sum of the two corresponds to the outgroup then have a high correlation to the gar similar to what they get for singletons so this for the genes which have a pattern like sub-functionalization whereas those which have a pattern like neo-functionalization the duplicates differ from the singleton so it's not the same and you repeat again this in zebrafish and medaka with slightly different scales and here they found evidence for overall sub-functionalization that's very nice it's a lot of data it would be nicer to finalize the question but the same year another group studied the salmon in genome duplication so they sequence the genome of a salmon which had a duplication the salmon salar the usual salmon and pike which is closely related to summons but didn't have the genome duplication and they compared the gene expressions like this so you have gene expression every column is a tissue a sample and every line is a gene and so you see that when you have a gene which for example here all these genes are highly expressed in the brain for one copy in salmon salar in the salmon highly expressed in the brain for the outgroup in the pike but much more lowly expressed in the brain for the other copy in the salmon and on the other hand they had high duplicate high expression all kinds of other places which was not present neither in the outgroup oops sorry nor in the first copy so this goes in the direction of saying that we have no functionalization we have repeatedly genes which have one copy which is like the outgroup and the other color which is different so these two groups have fought by different papers they use different methods different metrics so there is a paper by the salmon group which says if we realize everything it's clearly no functionalization and a paper by the gar group which says if we realize everything is clearly sub-functionalization at this point i would say i don't know and i'm collaborating with the gar people to get more data and try to understand but and there was also a paper more recently in aphioxus so aphioxus if you look at the phylogeny is the outgroup to the vertebra genome duplications and what we find here we cannot really distinguish so this is a complicated figure but what's important that when you have on the logs you can compare the expression in the tissue in the aphioxus to the zebrafish and what you often have is a kind of specialization so it's not really a sub-functionalization in the cartoonish way but more that one of the sorry two zebrafish copies is broadly expressed in more it's the same place as the aphioxus and the other is much more narrowly expressed and this is something we see a lot we also saw in the human mouse data although we didn't have an outgroup is that we have a lot of cases where when there's two duplicates one is lower expressed and more specialized and the other is higher expressed and more broadly expressed but how this relates to sub-functionalization and no-functionalization we don't yet know so this is something this third hour i'm sorry is full of question marks we don't have the full answer to the auto-conjection we don't have the full answer to neo and sub-functionalization that's research for you but i think we are refining our view and seeing that things are more subtle than the cartoon images we had 10 years ago so if i want to keep a few minutes for questions i will go to a conclusion slide so on average after genome duplication there is evidence for both sub and neo-functionalization and one of the things i think that people would like to do now is to understand better clearly both happen when do they happen is it because neo-functionalization happens more short term and sub-functional long term is it because different categories of genes are kept is it because some are at the expression level and some at the protein sequence level i didn't show you but there's starting to be some evidence for selection on the protein sequences also many genes do not diverge an expression i didn't show this too much in the slides because kind of boring pictures but in fact these slides are only a part of the picture here you have the genes diverge between the copies but someone has had many more genes than this they have about 40 000 because they had several genome duplications and most of them are actually all the same and we see this also for example in xenopus and we are studying a lot these questions on expression because it's i would not say easy but feasible tractable to get expression in different species across the whole genome and compare it other features of function are much harder so they're harder to get large scale and when we get them large scale they're harder to compare so we have limitations both on the experiment side it can be very difficult to do it's almost impossible to systematic knockout in any species which is not yeast or E. coli it's very difficult to do systematic protein-protein interactions it's very difficult to do systematic and most then features of function actually specific of subcategories of genes so if you have enzymes you want to study their the catalysis if you have receptors you want to study their ligands if you have transcription factors you want to study the genes they regulate but then this becomes much harder to put all together and by informatically as soon as you go outside of RNA-seq which already has biases then it becomes even worse like what i showed you for the genotology complicates also all the other things whether it's knockout phenotype whether it's protein-protein interactions whether it's enzyme activity all these things become very complicated to compare so i'm not saying we won't manage but it's clear that we start with expression because it was tractable so in conclusion of this morning thank you for listening first i see that some of you are still here so i hope i showed you that gene and genome location are quite common and so we should take them into account in comparative genomics i think i showed you that the evolution of function is hard to study i don't want to discourage you it also means it's interesting challenges make for interesting research so far as i was saying expression is the best studied proxy for function evolution it doesn't mean it's the best and maybe in 10 years we'll look back and say everything we did on expression was really crappy and lucky now we have a better way to measure function but that's what we can do now okay so we're like the tail of the drunk person who is looking for their keys under the streetlight not because they dropped the keys on the streetlight but because that's where there's light to look for keys and finally i hope i showed you that curated databases are useful and to study function we really need this curation and these structured databases thank you for your attention i will now look at the questions so questions questions are pseudo genes included in sub-functionalization no pseudo genes are included in loss of the gene so a pseudo gene is considered a step between losing the towards losing the gene in most cases so if you have two copies of the gene i showed you only the scenarios where you keep the two copies there's actually another scenario which was the most common one you have two genes and now you go back to one gene you lose and that's that exponential decay we had at the beginning of the morning and now how do you lose genes it's very rare that morica scissors come and chip exact cut out exactly the one of the two copies what happens that your mutations which little by little deactivate this gene so that it's not expressed it's expressed but it's not translated it's translated but it's not folding that at the top so you get a pseudo gene so the genes can be transcribed okay uh sometimes and the pseudo gene pseudo genes are basically uh duplicate genes being lost and actually this brings back to the question someone had earlier this morning if duplication is frequent we should see a lot of duplicate genes in the population and i spoke of copy number variants actually the pseudo genes and there's a bit less pseudo genes than genes in the human genome but close so it's like 19 000 to 17 000 sorry i don't remember the exact numbers the pseudo genes are all evidence for duplication which happened not so long ago and is being lost because once a pseudo gene has no function at all it's not under any purifying selection that will be a target for mutations which will occur and get fixed by drift without any selection to prevent them from getting fixed and so pretty fast you will lose them so it's you cannot compare autologous non-function sequences between a human and a mouse that's too far away because after 80 million years on each side so 160 million years total evolutionary time mutations scrambling so much that you lost everything and should know that in most at least eukaryotic genomes that i know small deletions are more frequent than small insertions so if you have a piece of sequence which is useless you basically lose it little by little just by deletions if you wonder why our genome isn't then much smaller it's because we also have transposons who come and increase the size of our genome but that's a different discussion um going to the questions okay does co-expression of two genes speak for sub-functionalization co-expression of two homologs or paralogs or co-expression of two unrelated genes paralogs so if two paralogs are co-expressed that says that that they share function so they it it's uh from an expression point of view it's would favor um just increase in in quantity now i know anecdotal stories whether it's shared expression with changes of function but it's hard to study large scale but for example um estrogen receptor invertebrates there are two genes estrogen receptor alpha and beta and they form a heterodimer and they express together and you need both paralogs to form the function heterodimer in some circumstances sometimes you need the homodimer actually and sometimes the heterodimer so the heterodimer has a new function and you have various cases like this the most well known is hemoglobin hemoglobin is an assemblage of paralogs which express together but have different sub-functions so yes this can happen but it's hard to characterize on a large scale because you can look at detail at one transcription factor one globin but to characterize this large scale is difficult would you consider duplication somewhat useful because we can compare them to an out group useful for what because it depends useful is useful for something i like duplication because i studied them so they're very useful to my career um but i'm not sure what the question is if this is the question i know some papers which use duplications as an additional phylogenetic information so they improve the species phylogeny by the dating of the duplication so that's the question i can give you some links to that yeah so i can give you a there are some methods which exist um and probably Christophe Desimone knows also some others which use the the the order of duplications in the phylogeny as an additional evidence for species phylogeny additional question as a rough measure can use the number of present absent calls in bg uh use it for what so use it as a measure of tissue specificity yes you can if that's the question yes and uh in our benchmark for um tissue specificity measures we showed this works not as well as a quantitative measure but not too bad and actually we're we're implementing this into bg but it's not yet on the website because before we put something on the website we have to verify it a million times so yeah is there a cause or biases of genomic analyzes seems like a vast and interesting subject the thing is once you look into it it's interesting but if we put this as a title no one will come so that's an interesting suggestion i don't know if patricia palagius here or not right now but uh yeah she's here i am she's coordinating the training at sib so we can take note of the question like you know when genomic uh methods don't work it would be fun to teach i don't know if a lot of students would come