Prof. Tom Gilbert, Copenhagen University, recently gave a talk during his visit to the CRC 1182 at Kiel University:
“Evolutionary Hologenomics – why many things I used to believe in might be wrong”
Tom Gilbert is the director of the Danish National Research Foundation Center for Evolutionary Hologenomics as well as the group leader of the Hologenomics group at the GLOBE Institute.
More on Tom Gilbert’s work: https://ceh.ku.dk/staff-center-for-evolutionary-hologenomics/?pure=en/persons/295003
I’m very happy to um introduce you Tom Gilbert uh Tom is a professor at the University of Copenhagen uh he’s director of the center for evolutionary Hol genomics and uh a Visionary a thinker uh interested in many different systems uh around the Holo the Holo Bion
And the Holo genome and uh I promise you an exciting and inspiring talk Tom the stage is yours thank you and thank you everybody for coming um I’ve actually been terrified for about six months about giving this talk to be honest because uh normally when I give a talk I talk to
People who don’t believe in the Hol genome and the hollow bant which is most of our colleagues the young people here won’t realize this but most of the old people in biology think it’s heresy so it’s rare if ever I’ve had to talk talk to an audience who could be viewed as
Converts and uh I was mentioning this to Thomas earlier so normally I’m like the missionary going to the heathens and preaching and possibly they’ll try and eat me or burn me or something today I’m kind of like the pope maybe preaching to the the masses which could be good maybe
You’ll be like hallelujah or maybe you’ll be rolling your eyes because you think it’s a load of rubbish but we shall see uh and for the record uh I’m uh I am based in Denmark I am a Dane now I didn’t used to be a Dane I run the
Center for evolutionary holog genomics which is a center that was funded uh to start in 2020 very much actually in light of the fact that that your issue here was funded because I could go to the fund and say this is not crazy look the Germans are funding it and there’s
Nothing Denmark likes funding more than stuff that Germany’s funding not least because of course K is a Danish University I’ve been told many times it’s like Denmark’s second or third University so basically we are the poor copy of of your initiative in ke in Copenhagen um yeah and also for the
Record I am an organismal biologist I uh studied biological sciences at Oxford which uh is very weirdly a bachelor of the Arts degree at Oxford still but I studied biology and actually I’m actually mostly a molecular biologist even worse I’m actually particularly bad at organismal biology I’m not a
Bacteriologist not a microbiologist by training a lot of what I worked on for most of my career was classic organismal biology microbes didn’t feature in there I I did a lot of work on Ancient DNA developing ancient DNA techniques doing systematics and population genetics and
So on done a lot of work on birds I do like my birds and I’ve done a lot of work on domestication in particular in the ancient DNA context although focusing on the organism the microbes if ever they surface they surface because when you work with ancient DNA a lot of
The DNA you get is microbial DNA not what you want and it’s a pain in the ass but then things changed 2006 we actually got money as the 454 was released the original 4554 that became the uh the the GS Flex we got money in Copenhagen to
Get one I apparently loved it so much I had a photo shoot with it I have no memory of this but I I wanted to find a picture of what was going on back then and I I know because I’m a molecular biologist this machine came out and I
Was like yes I want to get this and see what it does and actually the problem in 2006 was it was extremely expensive those who are old enough to remember this will remember that you for thousands of dollars you got 20 whole megabase of data right and it made life
Difficult unless you were working on humans or pigs or something very money based but I say I’ve been around long enough to see the Technologies change and more importantly to see the money bag get cheaper and cheaper and cheaper and today your regular field biologist which I occasionally am can take a
Relatively small amount of money and apply it to stuff and of course CU this was happening and it was getting about feasible really to do stuff financially by about 2010 11 I fully bought into what most of the world believe which is the genome will answer everything and I
Mean the Genome of the big thing you can see I mean this is actually a a cover of a recent nature a lot of people still believe this the answer is in the genome and much of what I did was about this so questions I was applying sequencing to
Were things like this how does X eat y for some reason how does a a vulture manage to eat nasty rotting carcass full of nasty rotting bacteria the answer must have been in the genome I thought right and in fact about 200 something this paper came out by by a group in
Korea they sequenced the Genome of the vulture they found genetic adaptations that allow the explanation of what’s going on and fulfilling my my idea that the genome is is is the answer to what’s going on here another classic question I’ve been interested in why are there so
Many of certain groups of animals and not so many of the others this is a philogyny of the uh the birds it’s basically representing the different orders of the birds one of the things about the birds about 65 to 70% of the birds are the pasarin why is it they are
So successful and not the other 40 or so orders to me the answer must have lied in the genome and actually this paper came out very recently by by a group and they’ve sequenced or they’ve analyzed the genomes of birds that actually we sequenced and they’ve done various
Comparative analyses of of the landbirds which is a very successful group and they argue that there are adapt ations based upon genes R to diet and vision and hearing and that explains what gives them this adaptive capacity here’s another one this is actually work that that that I did for
Many years with a post called Andy foot Andy is a kilwell guy I think they’re called orcas today kilwell is no longer a PC name and Andy was actually studying Sy Patrick speciation in action he was studying kilow whales from up off the west coast of California and these kilow
Whales do seem to be diverging from each other while living in the same environment in the same habitat which is strange classic Sy Patrick speciation and and Andy wanted to know what was going on so we sequenced the genomes of lots of kilow whales and we actually identified various mechanisms causing
Them to diverge or at least derived from them diverging and in fact coined a term called genome culture coevolution but the point was we were 100% convinced the argument was answered using the genome that that was that and one other last option uh sorry um example cuz I’m very
Interested in this domestication those that know your Evolution know that domestication is very very Central to uh to the thoughts that arose about Evolution originally Darwin looked at things being domesticated and sort of his ideas started forming and there’s of course been a huge amount of work on the
Genetics and genomics of domestication it kind of started early on when people like shashin limbad who’s a real Pioneer in genomics sequenced the dog genome for the first time and and she could compare the Genome of the dog and the Wolf to to ask questions such as how did X become Y
How did the wolf become the dog and and to be fair to the genomics people some of the answers they get can only be answered by The genome by looking at basically the genomic differences between them you can actually come up with good models of the process what was
Going on the fact there had been bottlenecks and so on and it’s very hard to do that any other way but many of the other insights they found were again classic genomic ones so here’s a paper by Eric axelon who was a colleague of mine for many years they were comparing
The genomes of dogs and wolves to basically answer the question how do dogs evolve to eat starch-rich diets which is not a very wolf-like thing wolves don’t normally eat starch unless they scare a hunter and eat their sandwich or something and what they’d actually managed to see was that the
Amalay gene which of course is very important for digesting starch has had a massive copy number expansion in dogs basically this just shows lots of copies of amas in dogs and it’s not expanded in wolves and therefore this is the answer this Ames copy expansion allowed dogs to
Start eating this diet that they got when they lived with humans and last example I thought I had done it but one more just to show an ancient DNA example I’ve I’ve worked on maze for a long time in particular the ancient remains of Maze and one of the questions
We were interested in was as maze was first domesticated in Hot Tropical Lan Mexico and then it was spread with humans up being taken to higher altitudes cooler altitudes drier altitudes what happened to it and actually by sequencing the genomes of ancient maze samples you can not only
Look at what genetic changes are happening through time but you can also see that a lot of the adaptations happening were coming because of introgression into ancient maze coming from Wild tier synas and this is a very common feature of domestication typically as domesticates are moved into new ranges they’re crossed deliberately
Or not deliberately with with wild variants that live there and they get genetic variation and that answers the question so all was good and I do want to make it very clear I do believe very much in genomes I’ve been very active in the uh the Earth bi Genome Project and
It’s various spin-offs and I even run a whole genome sequencing project in Copenhagen where we do reference genomes and for the least 13 years now myself and Goji Zang have been running b10k sequencing as many bird genomes as we can get our hands on if anybody here
Works on birds we now have 5,000 denova reference bird genomes we have 6 and a half thousand samples we’re missing 4,000 so if you have bird samples or if you want bird genomes please do talk to me because we give all our data away and we take samples and do genomes for free
So genomes are important don’t get me wrong I wasn’t completely wrong but my life took a very radical turn back in 2013 when I was doing genomes because I met Gary Gary is the bird curator in the Smithsonian and Gary actually introduced me to vultures which became a love of
Mine later and he introduced me by basically starting the conversation by going Tom do you know how vultures eat rotting carcasses and I was like No And Gary said well despite what they look like they have very weak beaks and very weak Claws and they can’t just open a
Carcass they have to stick their head up the anus and rip it apart from the inside which was kind of shocking to hear over dinner as we were eating at that point but but the point is that they stick their head up inside the rotting carcass full of all sorts of
Nasty rotting stuff right and so Gary’s like have you ever thought about it and I said no but I bet the answer is in the genome Gary and of course this genome paper came out and Gary said it might be but I’m not interested in genomes Gary
Said I’m interested in what are the microbes that end up covering the vulture when it’s doing this for a hobby right what’s the kind of natural skin microbes and gut microbes and that kind of sounded fun but I knew nothing about microbiology so I actually talked to my
Colleague lar hpia who was a microbiologist who had a willing PhD student and I was introduced to the magic of metabarcoding and I mean here metabarcoding for bacteria jumping a long way back in time we actually invented metabarcoding in a whole another context for Edna but I’d never
Done it on microbes and so we did this 16s study back in 2012 12 13 originally we sequenced using meta barcoding the microbes of two vulture species on the skin of the face and in the hinder and we made pie charts because that’s what everyone makes with this kind of stuff
And the interesting thing was there was a lot of this green and purple a lot of clust infuser bacteria which I didn’t know much about but when I said to L I was like what is this stuff and he’s like the kind of stuff you get gas Gang
Green from and the kind of stuff you find in rotting carcasses so no real surprise that the vulture that spent its life bathing in rotting carcass is eating it and covering it but the cool thing was we did have some Zoo turkey vultures who’ve sadly never enjoyed bathing in rotting carcass they they’re
Fed fresh chicken or giraffe or whatever the zoos feeding them at the time they were born from vultures that have never bathed in carcasses and they were born from vultures that were never bathed in carcasses and the faces and the gut of them are full of these rotten carcass
Microbes right now this was the first time for me I got really interested in microbes cuz I was like that’s weird why would these rotten carcass m micros be living on the vulture when they’re not doing the job and of course if you’re trained in evolution you tend to think
When you see something like that there’s got to be an explanation so Liz AA who was my uh most computational PhD student at the time begged to do some shotgun metagenomics and we we we we did shotgun metagenomics and she crunched all the data and cut a long story short she basically found
That on the face and in the gut there are bacteria that at least have the functions if they wish to use them to do various things so for example there is this fuser bacterium that basically is uh metabolizing buttino I think and there is a she looked at that and read
Into it a bit and said this is the kind of stuff which is known to have antimicrobial activities so maybe it’s maintaining this bacteria because it’s producing antimicrobial agents to take out other nasty pathogens we couldn’t prove it because it’s only based on mags but you know she said look there could
Be a mechanism there and she looked in the gut and she s saw some other things and she said look there producing things which are associated with biofilms and maybe it makes sense to maintain these bacteria to make a biofilm to protect the gut from the nasty stuff coming in
And she was basically arguing to me look I think these microbes are being maintained because they’re doing useful stuff for the host and again this is going to sound maybe stupid to a lot of people here because maybe you’re trained in the school of microbiology but for an
Organismal biologist I was like that is pretty weird and of course what we were basically seeing is what is now being termed and to be fair has been termed on and off since the 1940s a holic basis of adaptation to rotten carcass the question how does the vulture adapt to
Bathing in rotten carcass can only be answered through both the genes of the vulture and the genes of certain microbes and without both parts we don’t have the full picture and this of course is when the light bulb went off in my head and I was like damn you know we’re
Missing the point we’re focusing all on one part ignoring the other point being very confident writing covers to Nature about how we’ve got the solution and probably getting a lot of it wrong at best partially correct at worst completely wrong so again this was all back in
About 2014 2015 and of course microbes being important to animals and plants has been known for a long time I mean we we know they’re important in the gut for digesting things we know they’re important in cows for making methane we are there’s a huge industry today making
Probiotics for chicken and plants and dog additives and and of course there’s all sorts of interesting stuff coming out about the ways microbes can affect human health Beyond simply making you classically sick for example arthritis and so on and and this is all going on and it’s fine but again I’m an
Evolutionary biologist I don’t tend to be very interested in this but when we were having these well when I was having these Revelations that there was more going on than I’d been counting for in the genome this was the time all sorts of other studies started coming out
Including driven by people like Kevin who is here who will be talking about this kind of stuff later in the week where people were studying the microbiomes in various animals vertebrates the kind of things I look at and seeing the microbes con conferring on the animals all sorts of properties
That are Way Beyond regular diet and health right so sure that they affect nutrition is not a surprise but Kevin’s got a super nice study showing that they give toxicity resistant they allow these neotoma wood rat wood rats to eat stuff they couldn’t normally do there is a
This famous study out of a group in Sweden where they’ve actually taken brown bears and they’ve actually compared the microbiome of them when they’re awake and when they’re hibernating and they find differences and then they even manipulate mice with the microbes and sort of um start early stage hibernation there are studies on
Therm regulation there are studies on Behavior there are studies on all these kind of properties which are kind of important for the lives of animals and they’re super important if you’re interested in adaptation this slide for the record is something Charles Darwin never said but whoever said this said it better than
Charles Darwin right but when you think about Evolution there is this idea that the strongest doesn’t survive nor the more in intelligent but the one most responsive to change right it’s this idea adaptation is key said Charles Darwin didn’t write it he didn’t write it in 1809 when he was zero years old
Either I did Research into this it was written by a business studies Professor called Leon C megson who like to quote Darwin a lot but he did a much better job than the original Darwin quotation don’t even try and read it but it’s very long and rambly but it gets to the same
Point right adaptation is key and we have to bear this in mind if we’re interested in evolution if adaptation is key what is the key driver of adaptation what’s the most effective driver of adaptation is it the genome or is it something else and based upon this we
Actually wrote this little opinion piece myself and my colleagues arguing maybe we’re kind of missing the point maybe it’s the gut microbiomes of vertebrates that are giving these adaptive kicks that you need in order to adapt rapidly and the genomes are kind of secondary effect that maybe gets in later why is
It that microbes might be so important for adaptation of animals and plants well it’s basically about time if we think about the classic mindset of the geneticist thinking about the host genome and you ask them how does something adapt in light of changing environments well the answer is if it’s
Within the lifetime of the individual you can change gene expression you can turn genes on or turn them off or change the amount of things but ultimately to really make the changes you got to have babies you got to find yourself a partner you got to mix the DNA of the
Two parents make babies and so on hopefully you make a combination that’s a good combination and this can be a relatively fast process in rapidly reproducing animals it can be a very slow process in slowly reproducing animals like humans and whales and so on and of course the beauty of the
Microbiome as I’m sure everyone realizes is that we can change it so fast so if the microbes are conferring properties and given you can switch your microbiome extremely rapidly by changing your diet or so on you can introduce these adaptive properties so fast and therefore it must be a much more
Important thing for Rapid adaptation so in light of this then what I started thinking about was if I go back to these questions that that used to obsess me that I thought we’d solved using genomes I wonder if there’s a better explanation and what I will do now is give you my alternative
Explanation based upon microbes a lot of people hate these ideas uh luckily I sit at the top of the food chain in Denmark and I can have the ideas but uh junior people can’t have the ideas uh funding panels Ally hate these ideas but I’ll will present them and you can decide for
Yourself is it plausible is it not is it complete rubbish and so on so we’ll start with domestication right so if we think about domestication and microbes there are some sort of key questions one might want to ask oneself firstly do microbes change at all as a species is
Domesticated if they do can they have functional effects and might these microbes even be relevant to the initial domestication process itself could we do domestication without the microbes could these microbes even determine which species we actually domesticate so obviously the fact that microbes change during domestication is
Nons surprising as was made very clear in talks earlier today and as I think everybody knows microbes are incredibly sensitive to the DI in the environment this is just a summary figure from a human study only points takeway as of course you change your diet you have a
Big effect on the microbiome and of course one of the first things that happens when you domesticate things is get a new diet because they start Scavenging off human waste as opposed to eating whatever they eat normally so no big surprise the microbiome will change during domestication but is it more than
Just that and there is actually quite a bit of evidence now that the answer is yes so here’s actually a study I ran into it just a few weeks ago that I found quite interesting this is a study from Virginia Tech and at Virginia Tech they’ve been working with some chicken
That they’ve been selecting on for 56 generations to become very very tiny or very very large this is really quite a crazy crazy size difference and they’ve been studying these in a hologenomic way they’ve been studying the genomes of these and the microbiomes of them and they’ve been finding some interesting
Stuff so what they did was they they dissected out the guts of their chickens here is a chicken gut for those of you that like that kind of stuff they’ve then profiled the microbes at different parts of the gut and they’ve done some basic analyses so what you see for
Example the highweight line which is in red always has a higher microbial diversity than the low weight line doesn’t matter where you look so you know something interesting bear in mind these things are raised in the same facility fed the same food everything is equal apart from the fact that somehow
In their body there is selection on which microbes are there they actually go beyond just which microbes are there they basically look at the functions of the microbes and what this figure is basically showing is differences in the mean proportions of various functions encoded by the the microbes and the
Takeaways there are differences because they’ve sequenced the genome and the epigenome as well and the transcriptome to some degree they can even make nice inter interaction networks where they can identify variation in the Genome of the chicken and how that actually affects which microbes are present and
In doing so basically what the paper is showing this is not the first time this has been shown but it shows very nicely firstly the growth of the chicken is conditioned by the Hol genome it needs both the genome and the microbiome together to be affecting to get that
Phenotype and it’s a very fast trait but also that the microbiome is being shaped by the host genome so clearly this one AR icial situation it’s all about the Hol and the genome is not enough to explain what’s going on but what about other traits I mean growth is kind of
About nutrition and nutrition is kind of about microbes and it kind of makes sense so domestication is a very interesting trait sorry within domestication there is a very interesting trait which is tameness tameness is like the one universal trait what this figure basically shows is a
Load of domestic animals uh a load of traits that domestic animals have and if they basically have it or not if they have it there’s a green X and if they don’t they don’t and the main point is there is like one trait shared by everything and that is tameness and it’s
True tameness is like fundamental to getting animals to to live with us or at least cuddly animals maybe not goldfish I don’t know so of course this has been studied for a very long time at the the genetic front and genomic Studies have been done studying what are the kind of
Things that make the domestic animal differ and for example in dogs versus wolves there’s selection on a gene called MBP in uh in hes is it ZF mp1 and and in domestic foxes which we’ll come back to later it’s this sour S1 Gene and all of these genes are known to be
Important in behavior and fear and this kind of stuff and it makes kind of sense that they’ve been selected on and they explain what’s going on but the problem with all this is what we’re seeing here is the result of a longtime selection domestication wolves started to be
Domesticated 25,000 years ago and sure 25,000 years later we have all these changes in the genome that explain what’s going on but what I think people tend to ignore is the challenge of the early domestication cuz you know fine we originally had wolves wolves are aggressive nasty things you can’t live
Near them today we have these dogs that are fully adapted and their genome is changed yes that took 25,000 years but what about the first 1 2 3 5 10 15 generations of Time how did humans live alongside of the wolf before it picked up all these changes that turned it into
Something lovable and cuddly and slightly embarrassed like my dog in her nappy um but you know very rarely do people discuss this point right they kind of assume the Wolves and the humans came together and bingo Next Generation we had a dog which is just nonsensical
Right but that is the standard Dogma in what’s going on so we need some kind of explanation for how we affect this and this is a classic one where it makes much more sense to me that it’s about the microbiome given what we know today about the famous gut brain access which
Pretty sure everyone here knows about but the idea that your little microbes are factories in the gut pumping out chemicals that go up and affect the brain and affect the behavior and get affected back from the brain so can this be tested well this is the kind of stuff
That can be tested to see if it’s plausible so Lara here was one of our PhD students and Lara worked with a load of chicken that were created by a guy called P Yensen at ly sharping University in in in uh Sweden and peir got hold of red jungle foul uh and he
Selected on them for a number of generations to make them more aggressive and also more tame so like basically more chicken-like and less chicken-like and he found it went quite fast he studied the behavior he um sequenced the genomes and the epigenomes and saw there were changes in transcription going on
And so on and so on but what Lara did was she studied the microbiomes of these and the really important point about this kind of study is again these chickens are raised in one facility on the same food they live together they’re not even in separate pens right so the
Environment is completely standardized and what Lara wanted to see was do we get differences in the microbiome despite this homogenity and the answer was yes very very clearly yes so basically they have exactly the same microbes within them but there are clear differences in the relative abundance of
The microbes and this is actually heritable across Generations so for example the high fear lines of chickens have got relatively more of these lactobacilli and while we can’t say what they do in chicken there are studies on things like dogs showing that they they’re associated with fear uh in dogs
So interesting observation there and for example in the low feir line there is an abundance of clustal which have been shown in other animal systems like rats to be associated with happiness so there does appear to be this kind of selection happening on the microbes correlating with behavior it does raise the question
Of which way around is it happening oh not again sorry anyway so going back to the chicken so so you know we we saw this we saw this result and uh you know again normally when you see differences between these kind of things what somebody will say was well of course
There’s a difference because fearful dogs for example are fearful because they’re treated in a certain way and fed a certain kind of food and so on in the environment is different but when you see it in a very controlled situation it is somewhat harder to explain what’s going
On luckily I can remember my slides despite having so many so what Lara did after this was she actually said well okay this is one system is chicken what else is there out there what’s more closely related to dogs which is the system we care about and at this point
We got hold of samples from the bell of foxes and I don’t know how many of you have ever heard of the bell of foxes bellev was a researcher in the Soviet Union in the 50s in Nova SEK he actually got hold of foxes from fur farms in the
Baltics and these foxes were acclimatized to being in a fur Farm which is already different to being world so they were you could argue they were semi-domesticated but he got these f foes and he brought them in and he did the same kind of experiment on the foxes
He basically every generation looked at the baby foxes scored them on some kind of measure of tameness were they like hissing and trying to bite him or were they kind of licking or so on there we go and uh thank you uh so yeah so this
Is bellev he he got his foxes and he basically uh you know selected on them and they’re a classic study in domestication we know that after many well actually after only a few Generations they started to diverge in phenotype but basically after a number of generations they ended up with a line
Which are these uh so-call tame ones that you could actually buy until Russia invaded Ukraine and they you know something like5 $10,000 and they’re very doglike they they’ve changed phenotype completely their their voice is different they they don’t smell like a fox anymore they’re their tail curs
They’ve got these patches on and stuff and then they’ve got these ones here that you probably could buy to give to somebody you don’t like but they’re not very nice if there was an illegal circuit in fighting foxes they will be the ones you want they’re really very
Aggressive stroke fearful which is not always a different thing so so what Lara did was she she analyzed the microbes in these things and she again just like the chicken saw that although these things are raised in a standardized environment and they’re fed the same food and they’re allegedly
Never handled or anything there are differences in in the microbiome and what she actually uh she showed there was there was differences in the relative abundance and actually this is a figure she made what we have up here are what are called gut brain modules these are just basically various
Properties encoded by microbes that do things that are important for behavior and these are basically various microbes that are present and the important thing is if one looks at the the colors that kind of shows you where there’s a a significant and kind of reproducible difference and if you dig into what they
Are you find things for example like in the the happy Fox’s uh genes that are there to encode butyrate synthesis and this is in interesting because butter rate synthesis is known in both humans and animals to reduce aggressive behavior in Juice calming which is the
Kind of thing you would need to make a happy Fox and there’s a glutamate degradation which has been linked to reducing aggression and so on and interestingly several of these things are also the kind of things she was seeing in chicken so there seems to be the same situation happening again that
Although they’ve only been selected on for relatively few Generations there is Divergence in the microbiome so really what is going on seems to be a hologenomic angle and actually the the genomes of these foxes were published a few years ago and I already mentioned this a bit earlier one
Of the key differences in the genomes of the fox lines is this receptor for sorc S1 which actually is a receptor that binds to glutamate right so we seem to have this this nice system that the microbes are being selected on in the calm line to make this glutamate and
Then there selection in the genome on a receptor for glutamate it’s fitting together very very very nicely it doesn’t answer the question of why are there differences in the microbes we’re still seeing an end product but if you do read The genome paper of the the fox it’s full of all
Sorts of genes to do with behavior and the brain and stuff all this very exciting stuff and then there is this little half sentence towards the end and it actually says you know we see all these behavioral differences and then the immune system is different as well
And they leave it at that but of course differences in the immune system are probably super important for affecting the microbiome so my guess would be what happened early in the selection was that these foxes that as kittens in the early Generations that showed some kind of variation in Behavior actually had
Differences in the genes in the immune system and that in turn affected the microbes and that in turn affected the behavior and it started this cycle of change so it could at least be an alternate explanation for how very early in the domestication we changed the behavior of
Wolves so that we could live alongside them so that we could select on their genome for enough time to make a dog so I kind of view it as a kind of drugging essentially it does raise the question how could you do this how could you drug
A wolf luckily wolves are basically dogs and one thing that all dogs love to do is eat feces I don’t know how many people own dogs here if my dog runs into the bushes in the park it’s almost certainly found human and given that the model of domestication that we
Think is most likely is that wolves started to move in closer and closer to humans because they were running out of megap fora to hunt as wolves moved into humans they probably started Scavenging around human camps humans even back in the Paleolithic did not crap in single
Places they were very you know crapping everywhere probably throwing rubbish everywhere so it wouldn’t be a huge surprise that the wolves and their young in particular would have the ability to Feast on human microbes therefore modify them it could be a long stretch but at least the data is consistent that it
Could be a pathway for what’s going on if this is the case one can also ask the question why why did we domesticate the wolf and in fact not any of the other canids so you know the wolf is one of a group of what we call Crown canids
That include things like the coyote and the African golden wolf and the golden Jackal and the black black Jackal and so on and from the point of view of humans having a useful pet they would have all been great we lived alongside most of these in Africa and these things are
Good at hunting they’re good at guarding they’re sociable so one just have to wonder what was it that that was the wolf that made us first domestic at it was it a technological transition did uh humans 25,000 years ago suddenly think I’ve got a good idea I’m going to
Domesticate a wolf was it environmental or was it that maybe these other species are just completely untameable could it simply be that these other species either don’t like to eat feces or if they do eat feces they’re genetically not compatible with taking the microbes up and being affected by the the
Compounds they produce it may seem like a bit of a long shot but there are ways you can at least model this and the way we like to think about it is is a concept we call microbiome space and microbiome space is a property which is basically drawn from ecology and it
Helps us think about the differences in the microbes that not only do live in an organism but could live in it so if you imagine you know all the microbes that are that could live in an environment the environment could be the piece of paper in front of you it could be the
Ocean it could be anything you could lay them all out in front of you and you could be aware of the potential of being there or not and you can just draw yourself a nice grid and in this case I’m just going to color in squares each
Square is a microbe and a dark color is the microbes there and very abundant a light square is it’s absent now what we like to think about is how does the host genome determine the microbiome space of any individual so for example I might right now have a microbiome space that
Could in theory allow a whole range of microbes they may not be there because I haven’t eaten Danish food for breakfast or I haven’t changed my di or whatever but but the point is microbes from the outside could never be in there I could never have a cable bacteria living
Inside me it doesn’t fall in my microbiome space now what’s inside you will change all the time but ultimately they are constrained by the space what we’re really very interested in in our Center is how does differences in the host genome actually determine the overlap of space between individuals and
In fact the differences in space that one individual has and the other one doesn’t have because these are the kind of things that could be important for evolution and properties if red individual can have a new microbe living inside it CU genetically it’s compatible with it and if that microbe can make it
Super aggressive it can get a new behavior that could be important for evolution if a green individual could have a microbe that red can’t and it allows it to change its diet that could also be a property that could maybe be useful for for evolution so basically going back to
This question why the wolf and why not anything else maybe simply the answer is that the generic canid microbiome space as encoded by the generic canid genome is this maybe genetically the wolf is slightly different and can work with some different microbes and maybe just
One of those microbes is one of the ones that affects and change the behavior this is very very hard to test right now but we are trying to work on mechanisms to try and test this kind of thing without doing things that are too unethical to accept this you do have to
Accept the idea that genetics significantly shapes the microbiome and this has been very controversial for a long time a lot of people don’t like this idea obvious ly it’s a it’s not even a question at the between species level I mean if you just for example compare the microbiomes of monogastrics
And ruminants and H gut fermentors of course they’re different because their guts are completely different structures and of course the structure of the gut shapes the microb no big surprise there if you’re a plant person exactly the same thing different root structures will have different microbes simply because the structure is different the
Disagreement is about the within species level intraspecific and the disagreement has arisen partly because the initial studies were done on things like humans which are Dreadful study sets I mean this is just one of the early papers they were profiling the differences in the microbiom of different communities
And of course they’re different because they’re living in different places and eating different things and therefore you can’t go much Beyond it here’s an similar example from crops this is just showing barley I think from Israel and they see that the different barley from different locations has got different
Microbes but of course they’re grown in different geography no big surprise one of the beauty though of course of lab work and uh in particular working on domestics that are very tractable you can test this directly so this is a really simple Master’s study a master student project that was done
Over a couple of months what the student did was he just basically got a hold of five different land races of maze he grew them in the greenhouse on exactly the same soil in the same conditions for uh 3 months he then sequenced the root microbiomes and he just looked at the
Microbial communities and whether he’s looking at for example A diversity of the mic microbes or just looking at them in some kind of PCA it’s very very clear that the Genome of the land race is selecting on the microbes differently and therefore having an effect so this
Is not hard to prove whether it’s significant is another question but if this is happening one can start to then think about questions like this so these land races we were testing are shown on this map here basically it’s the uh is you can see there in different distributions of the
Americas and legitimate question in in May biology is why what’s driving this is it the uh genetic variation of the host and if it is what is going on I actually wonder if the answer again lies in the microbiome space maybe if one was to think about which microbes these
Crops can actually work with as encoded by The genome if you end up with something like this that for example ones that grow in a very very unique environment are adapted to a very specific cluster of microbes and the ones that grow in other regions that have overlaps have some overlap but some
Differences and and if you think about things like b73 b73 is like a super maze that will grow everywhere maybe what makes it a super maze is that it’s able to work with a really really broad range of microbes and that explains its distribution and again one can start
Thinking about this and applying it to all sorts of other questions so this question I started at the beginning passerine diversity why are 65 to 70% of the birds this one group could it simply be that they can work with a much much wider range of microbes than any other
Bird which gives them the ability to basically eat more things or explore new habitats so maybe there’s a relatively narrow diversity of microbes associated with most birds but maybe the passerine can explore a huge potential within this microbiome space and this allows them to adapt to all sorts of new diets this is
Actually difficult to test there is data that one can explore this is data from Sarah herd that she published a few years ago it’s basically a principal component analysis of the microbes found found in different birds and they’re colored by different orders the performs are this order that’s the very very
Dominant one and you can see they’re all over the place the problem of course is that these birds are already eating different things and in different locations so the ideal situation would be that these birds are raised in the same conditions and tested to see what’s
Going on that’s very hard to do another problem is that many of these samples are non-standardized this is the classic microbiome Horror Story we all know about that if somebody else collects samples and treats them in a different way the data is very uncomparable in
This regard I do want to briefly flag a project being led by my colleague Anton alberi he’s pushing this thing called the Earth Hol genome initiative where he’s trying to collect standardized data across a huge number of um vertebrates it’s a very collaborative project uh they basically ship collection kits to
People who do animal work and they basically been collecting around the world and they’ve got some very beautiful figures on their pages but at this point they’ve received about 6 and a half thousand samples from 230 groups for 150 species and these are fully fully fully standardized and this is key
Because if you want to start making these comparisons you need that standardization so if anybody is working on vertebrates and is interested in standardized data Anton is the man to contact I think my last example I want to go back to is the the hardest one for
Many people to accept which is the sympatric speciation so again as I mentioned these Kil Welles are very interesting because although they all live in the same location off the west coast of the US they do appear to be diverging from each other they’re not having any reproduction with each other
They’re forming new species and it’s really hard to explain how this can go on but one of the interesting things about these is these three types of Kow whales that are diverging have got very very different diets and they’re very specific on what they eat one of the
Groups eats fish one of them eats marine mammals one of them eats birds and why is this important well it goes back to this point that has been covered several times today diet clearly affects the microbiome and of course the microbiome can affect the brain so what I actually
Wonder could be going on is is this initial preference for diet basically affecting in some way the brain through the gut brain access and leading to reproductive isolation essentially driving a lack of preference for things that are not eating the same diet sounds kind of crazy but there is a little bit
Of evidence coming out I found this paper a few years ago about actually diet gut microbes and host mate choice I got very excited until I found it was about dropil but on the other hand if it works in drop it may well work in other things as
Well so what is all the point of this well essentially I do believe more and more and more that if you’re an evolutionary biologist interested in organisms you absolutely have to take the microbiome into account because you absolutely will not get the right answer otherwise of course that’s just the
Evolution I mean there’s growing evidence that it’s the same in medicine if you want to for example treat people with microbiomes you probably have to take host genetic variation into account it’s got equal relevance for crops and and domestication and so on and I really do hope more and more people will
Embrace this uh Thomas and I had a chat about this earlier and Thomas is not feeling so positive that the rest of the world will eventually embrace the union of the two but I hope that that’s just the old people who will die because their microbiomes are not good enough
And the young people with the vigorous micro biomes we’ll take it over so this is why essentially I spend a lot of time going around the place and uh to paraphrase the Mandalore and say this is the way stop looking at one or the other and I’ve always felt very good about
Doing this but on the other hand I I’ve kind of come to the realization when reading the web page of your Center that your aim is to understand why and how they enter into the connections and what consequences they have which is all I’m talking about so those of you that again
Know the Mandalorian you will know he never takes his helmet off but if he did it would be Thomas Thomas is the way so so thank you Thomas because I I think you’re doing a hugely great job for pushing this and of course you have your
Book and so on but just holding meetings like this I think is super super important and getting people schooled in this thought the best thing that can happen to me is that everybody here goes that was really boring because we know all this already because that shows Thomas has
Won uh I will say thanks but I want to end with the last thing you’re not the only guys with a conference we are holding in Copenhagen a conference next year 3 days in June um it’s free it is the applied Hol genomics conference basically it is a conference where there
Is a number of speakers who are coming who work with extremely different tools state-of-the-art tools and they are applying them to all sorts of interesting questions some of the questions are applied some are health related some are evolutionary summer conservation and so on it’s basically a
Place to go if you want to go and actually see what can be done and get ideas we did do it once before a few years ago Manuel was a speaker at that one for example and it got a lot of uh interest there’s a very interesting range of speakers coming this time
Including Thomas he’s actually I think the lead speaker of the lot so um please do consider coming I say it is free Copenhagen is expensive I agree but you can camp um but apart from that the conference is free actually Connie I think used to also be here and she’s one
Of our speakers so if you want to know more we have a website we have a ex account and so on but please do feel free to come and with that thank you I hope it wasn’t too [Applause] long