thank you to brilliant.org for supporting PBS what makes us human is it the way that we walk or talk or think or invent is it the cultures that we create and transmit is it the way we interact with our environment is it all of the above or something else entirely we've been asking this question for a long time from a lot of different perspectives from anthropology to religion to psychology to philosophy rarely finding simple clear-cut answers but over the last few decades an entirely new method of introspection has emerged we've become able to search our DNA for the Hallmarks of human uniqueness at the genetic level so you might have heard that our genes are around 99 identical to those of chimpanzees our closest to living non-human relatives so what's the net remaining one percent that encodes Humanity as simple as the question sounds answering it has proven to be a decades-long quest that is still far from over and along the way we've had to change how we think about genomes altogether because in the search for the genes that make us human some of the most important answers were hiding not in the genes themselves but in what was once considered genomic junk now genetics can sometimes feel like a part of modern science that's easy to take for granted but compared to paleontology or geology or anthropology genetics is still a very young field I mean even the now iconic double helix structure of DNA was only revealed to the world in 1953 which is within living memory for some people and the search for human genetic uniqueness only really began in Earnest in the 1970s when scientists became able to zero in on individual DNA sequences at first we assume that the big important differences between us and chimps the sequence is responsible for Humanity would be mostly or entirely found within genes technology at the time meant that deciphering even short stretches of the A's T's C's and G's the bases that make up our DNA was time consuming tedious and expensive human genomes were over 3 billion base pairs in size so the idea of sequencing and studying the whole thing seemed like a futuristic sci-fi dream for much of the second half of the 20th century so instead we had to carefully pick individual bits of the genome to analyze and because because of that it seemed natural to start with the ones that actually code for proteins aka the genes now there is also a pervasive idea at the time that genes were where everything that was biologically important happened and the rest of the genome could be largely written off as non-coding non-functional junk DNA and this approach of looking at the genes did reveal some key differences like in Fox P2 for example a gene that seems to play a role in the ability to speak box B2 has picked up some important mutations in Arrow lineage since our last common ancestor with chimps around 6 million years ago and a number of other genes that we share as our closest primate relatives have undergone changes too like being turned off on our genomes or being duplicated or changing location but as cool as those examples are they alone can't neatly Define or explain our Humanity even early on researchers noticed that human genes and proteins generally had very few differences from the corresponding ones in chimps far fewer than they had expected and it seemed like far fewer than code account for all the differences that we see between us the plot thickened in the early 2000s when we finally got a good look at an entire Human Genome before the Human Genome Project was completed some researchers predicted it would reveal around a hundred thousand Gene a large enough number to account for all of this magnificent complexity but it turned out that there are only around twenty thousand to thirty thousand genes and these genes made up only one to two percent of the genome it was non-protein coding DNA the so-called junk that represented most of the rest okay and here's what bothers me we have fewer genes than grapes or water fleas like I don't even know what a water flea is but grapes are the things that like my kids would throw on the floor from the high chair they have more jeans than I do that's how it's going to be okay my point is this is both humbling and confusing I mean how could we humans be so complex if we have so few genes and they're mostly the same as those of our closest living non-human relatives well a few years later in 2005 the chimpanzee Genome Project also produced its first draft sequence having both human and chimp genomes as well as other more distant relatives like mice allowed us to compare not just our genes but our non-coding regions too see some experts suspected that there were sequences hidden in the junk DNA that were actually functional not because they directly coded four proteins like genes did but because they somehow regulated the activity of those genes and changes in those regulatory sequences that were unique to humans could be just as important or even more so than changes in the genes themselves after all genes are basically just biological tools and you could use the same set of tools to build a table a chair or a figurine it all comes down to how you use them to sift through all that non-coding DNA for sequences with actual functions and separate them from the junk we look for signs of conservation across vertebrates see all DNA sequences pick up random mutations and if a sequence is doing something important that's generally bad news because mutations often disrupt that function so over evolutionary time natural selection Works to purge those mutations keeping the important sequences very similar even between distantly related species much more similar than junk sequences which can accumulate random mutations and diverge between species more quickly because they have no functions to maintain and in 2006 researchers identified around five percent of the human genome that was non-coding but tightly conserved across species which means some of it probably plays important regulatory roles think of these sequences as switches that control the activity of genes and those switches have been around in the non-coding DNA of vertebrates for a long time and are generally very similar between species but in humans thousands of them have been tweaked altering the way they work and how they control our genes scientists call them human accelerated regions or hars many of them are associated with brain and nervous system genes changing how those features develop compared to our closest non-human relatives like chimps okay so search over right Humanity comes down to some mutations in the one to two percent of the genome that's made up of genes plus a bunch of tweaks in the five percent that regulates genes job well done everyone we can go home well not quite in a paper published in 2022 researchers announced that they had found yet another previously unknown layer of the genomic onion they expanded their search to the rest of the genome the more than 90 that is both non-coding and not conserved and in that bubbling pool of fast mutating junk they found something incredible entirely new regulatory sequences that are unique to us they've been forged from sequences that used to be drunk DNA they weren't conserved in other species so we'd missed them in our previous searches the researchers call them human ancestor quickly evolved regions or hackers good work marketing team hackers were about as unique to humans as it's possible to get in other species many of those sequences don't seem to do anything but in our ancestors genomes they'd been converted from junk to functional and what's more these hackers were the the fastest evolved regions of the entire Human Genome they had emerged quickly sometime after our lineage split from the chimp lineage but before we split from our close relatives the Neanderthals and Denise events okay but what do these hackers do well the nearly 1600 hacker sequences are most commonly associated with regulating genes involved in the immune system the gut and the Brain now the immune system evolves rapidly because it's locked in a never-ending game of cat and mouse with pathogens that it has to constantly adapt to but the gut and brain connection pointed toward a long-standing idea in anthropology the expensive tissue hypothesis this hypothesis suggests that the reason our brains are unusually large and our guts are unusually small compared to other great apes is that both of these tissues require a lot of energy I would not call my gut small but that's what we are it was an evolutionary trade-off and our ancestors went in the direction of big brains tricking our guts to balance out the energy cost so finding that many hackers affect the expression of both brain and gut related genes but actually makes sense when we look at our differences with chimps we have come a long way from our early assumptions about the importance of genes to our more recent realization that non-coding DNA might not be totally useless after all maybe the thing that we've really found in our search were the genes that make us human is that it's actually the genetic raw material the junk DNA that's most useful to have in your genomic back pocket it's like the stuff in your drunk drawer at home that you keep around like not because you need to write this second but because one day it might come in handy suddenly it's no longer junk ultimately the search for human uniqueness at the genetic level has turned out to be more difficult than we'd hoped more complex than we had imagined and more humbling than we ever expected because even though the differences between us and chimps might only be a tiny fraction of our DNA our complexity may not actually be about how much unique DNA we have but instead about the still murky ways that DNA operates and in that sense the search for what makes us human still has a very long way to go thank you to brilliant.org for supporting PBS brilliant is an online learning platform for stem with Hands-On interactive lessons brilliant is for Curious Learners both young and old professional and inexperienced brilliant courses teach you how to think via interactive lessons and problem solving activities and exercises and solve problems with interactive lessons in stem today's world is unpredictable but by learning something new every day you gain the knowledge to interpret information around you for example brilliant.org offers a course called the knowledge and uncertainty this course gives you tools for managing uncertainty and interpreting information you will learn Cutting Edge mathematics like information Theory Bayesian networks and Casual inference but without calculations getting in the way the emphasis is on applying these ideas to deal with the uncertainty in your life to learn more about brilliant go to brilliant.org eons Riley J mengan a PhD candidate at Duke University helped us with this episode and our staff writer Farhad Mitha had a chance to record an interview with him about his work on human evolutionary genomics and we're making that fascinating discussion available for our patrons check it out now over at patreon.com eons if this got you thinking about how we became us be sure to check out our human evolution playlist that covers topics like our place in the primate family tree and when we lost our refer also thanks to this month's genius eontologists Gail Brown 1M jaxy Weiss Melanie lamb Carnival Rafael Hossa Annie and Eric Higgins John Davidson ing Jake Hart and Colton by becoming an ionite at patreon.com eons you can get fun perks like submitting a joke for me to read here's one from Stefan Rooney what's 10 meters long has scoots on his back and it hurts like heck when you step on it a Lego Soros that's a good one it's like if there's a bad Lego dinosaur joke I have not heard it and as always thank you for joining me in the Adam low Studio subscribe at youtube.com eons for more adventures in deep time [Music] the expensive tissue hypothesis it sounds like the name for a prog rock cover band I would I would see that band the expensive tissue hypothesis they're really good you got your yes you got your Pink Floyd Emerson Lake and Palmer they're all in there LOL