1 00:00:00,160 --> 00:00:14,750 [Music] 2 00:00:21,380 --> 00:00:19,820 hi everybody I want to thank arena and 3 00:00:23,330 --> 00:00:21,390 the conference organizers for putting on 4 00:00:24,500 --> 00:00:23,340 it's already at the first day a really 5 00:00:28,550 --> 00:00:24,510 awesome conference I've really been 6 00:00:30,770 --> 00:00:28,560 enjoying all the talks today sorry about 7 00:00:34,220 --> 00:00:30,780 my complicated title I really want to 8 00:00:35,450 --> 00:00:34,230 talk to you today about kind of recent 9 00:00:36,770 --> 00:00:35,460 concepts that I've been considering 10 00:00:40,010 --> 00:00:36,780 about energy conservation and energy 11 00:00:41,720 --> 00:00:40,020 flow through the first cells and this is 12 00:00:44,030 --> 00:00:41,730 kind of preliminary data that I'll 13 00:00:46,040 --> 00:00:44,040 present a small amounts of that and some 14 00:00:48,500 --> 00:00:46,050 concepts that I hope can foster some 15 00:00:50,210 --> 00:00:48,510 discussions with everybody and so what 16 00:00:52,310 --> 00:00:50,220 I've seen today and I hope to see during 17 00:00:53,930 --> 00:00:52,320 the rest of the presentation or more and 18 00:00:55,340 --> 00:00:53,940 more puzzle pieces that we might 19 00:00:57,590 --> 00:00:55,350 eventually be able to put together and 20 00:01:02,119 --> 00:00:57,600 have a better idea of how how this got 21 00:01:03,439 --> 00:01:02,129 started so when I think about what the 22 00:01:05,930 --> 00:01:03,449 first cells were doing and what their 23 00:01:08,719 --> 00:01:05,940 first Physiology was I I often remember 24 00:01:11,719 --> 00:01:08,729 that all life is using energy in the 25 00:01:12,950 --> 00:01:11,729 form of chemical potentials and putting 26 00:01:15,020 --> 00:01:12,960 that through the cells and organizing 27 00:01:17,330 --> 00:01:15,030 the cells that way of course there's 28 00:01:19,160 --> 00:01:17,340 photosynthetic cells but light converts 29 00:01:22,160 --> 00:01:19,170 chemicals into high-energy molecules and 30 00:01:24,680 --> 00:01:22,170 those are subsequently used sometimes 31 00:01:26,540 --> 00:01:24,690 it's convenient to divide energy flow in 32 00:01:28,790 --> 00:01:26,550 biological systems to a maintenance 33 00:01:31,400 --> 00:01:28,800 process that is how much energy does it 34 00:01:32,750 --> 00:01:31,410 just keep me just does it take for me to 35 00:01:35,330 --> 00:01:32,760 stand on the stage or if you're a 36 00:01:36,980 --> 00:01:35,340 microbe just to sit there and do your 37 00:01:38,840 --> 00:01:36,990 thing and then there's the reproductive 38 00:01:41,480 --> 00:01:38,850 cost which is really really high I don't 39 00:01:43,580 --> 00:01:41,490 have kids yet but I hear having having 40 00:01:47,030 --> 00:01:43,590 offspring is hard it's also hard if 41 00:01:48,560 --> 00:01:47,040 you're a microbe I assume but these are 42 00:01:50,780 --> 00:01:48,570 the kind of the two different pies that 43 00:01:54,230 --> 00:01:50,790 we can divide energy flow through when 44 00:01:57,020 --> 00:01:54,240 we consider life and so a really 45 00:01:58,340 --> 00:01:57,030 fascinated question for me is is what 46 00:01:59,899 --> 00:01:58,350 are the first energy flows that 47 00:02:01,550 --> 00:01:59,909 organized material in a way that 48 00:02:03,500 --> 00:02:01,560 resulted in what we call biology today 49 00:02:06,350 --> 00:02:03,510 and that's kind of what I what I really 50 00:02:08,509 --> 00:02:06,360 want to talk to you about us biologists 51 00:02:11,210 --> 00:02:08,519 we use kind of funny calm very funny 52 00:02:13,009 --> 00:02:11,220 words to talk about energy flow and we 53 00:02:15,170 --> 00:02:13,019 we use this term called energy 54 00:02:17,420 --> 00:02:15,180 conservation and it took me a long time 55 00:02:19,970 --> 00:02:17,430 to really understand what that meant and 56 00:02:22,280 --> 00:02:19,980 so I want to talk about that in a very 57 00:02:23,509 --> 00:02:22,290 basic way with you today so that we can 58 00:02:28,730 --> 00:02:23,519 all get on the same page about what it 59 00:02:30,980 --> 00:02:28,740 means it really means saving energy and 60 00:02:33,320 --> 00:02:30,990 losing energy to the environment in the 61 00:02:35,360 --> 00:02:33,330 form of heat and just dissipating it 62 00:02:37,940 --> 00:02:35,370 using the energy from the environment 63 00:02:39,830 --> 00:02:37,950 from sets of chemical reactions temper 64 00:02:43,640 --> 00:02:39,840 to temporarily hold matter in an 65 00:02:45,650 --> 00:02:43,650 organized state so sometimes I think 66 00:02:47,840 --> 00:02:45,660 about it more in terms of how can a 67 00:02:49,730 --> 00:02:47,850 chemical reactions save energy during 68 00:02:51,350 --> 00:02:49,740 the reaction progress if you talk to any 69 00:02:53,420 --> 00:02:51,360 biologists about it they'll say oh the 70 00:02:55,220 --> 00:02:53,430 energy conservation works this say this 71 00:02:56,900 --> 00:02:55,230 way or it works that way and you might 72 00:02:58,760 --> 00:02:56,910 ask what does it mean to conserve things 73 00:03:00,920 --> 00:02:58,770 I would encourage you to think about 74 00:03:03,530 --> 00:03:00,930 like oh the organism is saving energy 75 00:03:07,040 --> 00:03:03,540 along that reaction and it's organizing 76 00:03:11,480 --> 00:03:07,050 itself temporarily with that flow and so 77 00:03:13,010 --> 00:03:11,490 I'm gonna talk about possible energy 78 00:03:14,300 --> 00:03:13,020 flows that might have been occurring at 79 00:03:17,330 --> 00:03:14,310 hydrothermal events that might have 80 00:03:20,060 --> 00:03:17,340 organized material in the very from the 81 00:03:21,320 --> 00:03:20,070 start it doesn't mean that I think that 82 00:03:22,310 --> 00:03:21,330 hydrothermal vents are the place that 83 00:03:23,960 --> 00:03:22,320 life happened but I think they're 84 00:03:27,230 --> 00:03:23,970 interesting to consider because there's 85 00:03:30,380 --> 00:03:27,240 a sustained source of energy that flux 86 00:03:32,360 --> 00:03:30,390 coming out of them and because I chose 87 00:03:35,650 --> 00:03:32,370 to talk to you today about hydrothermal 88 00:03:38,810 --> 00:03:35,660 vents and the origin of life I wanted to 89 00:03:41,680 --> 00:03:38,820 just quickly bring up and go through a 90 00:03:44,000 --> 00:03:41,690 recent paper that also just discusses 91 00:03:47,000 --> 00:03:44,010 energy flow and physiology that's 92 00:03:50,600 --> 00:03:47,010 happening at hydrothermal vents and I 93 00:03:51,860 --> 00:03:50,610 want to do this because since I think a 94 00:03:53,390 --> 00:03:51,870 lot about hydrothermal vents and the 95 00:03:56,090 --> 00:03:53,400 origin of life and also contemporary 96 00:03:57,820 --> 00:03:56,100 life people recently asked me about this 97 00:03:59,900 --> 00:03:57,830 paper and what do I think about it and 98 00:04:03,140 --> 00:03:59,910 I'll tell you what I think about it in a 99 00:04:04,970 --> 00:04:03,150 couple slides here the goal of this 100 00:04:07,370 --> 00:04:04,980 paper was to analyze all contemporary 101 00:04:10,130 --> 00:04:07,380 genomes and find out what is the common 102 00:04:12,620 --> 00:04:10,140 set of proteins or enzymes that are 103 00:04:16,430 --> 00:04:12,630 found in the last common ancestor of 104 00:04:18,020 --> 00:04:16,440 bacteria and archaea and say and to be 105 00:04:19,729 --> 00:04:18,030 able to use that information to comment 106 00:04:22,160 --> 00:04:19,739 on what the physiology of that organism 107 00:04:25,370 --> 00:04:22,170 was you can argue whether or not that's 108 00:04:27,440 --> 00:04:25,380 a valid approach at all as in does it 109 00:04:29,450 --> 00:04:27,450 make any sense or how much sense how 110 00:04:31,100 --> 00:04:29,460 sure can you be just from genome 111 00:04:32,330 --> 00:04:31,110 analysis when you're talking about 112 00:04:34,190 --> 00:04:32,340 something that happened around four 113 00:04:36,200 --> 00:04:34,200 billion years ago but it's one way to go 114 00:04:37,580 --> 00:04:36,210 about it presumably there is a record 115 00:04:40,490 --> 00:04:37,590 contained in our genome that we can 116 00:04:42,110 --> 00:04:40,500 derive information from and the way that 117 00:04:42,470 --> 00:04:42,120 these authors chose to do it is quite 118 00:04:44,210 --> 00:04:42,480 some 119 00:04:46,760 --> 00:04:44,220 and it's nice that they made it simple 120 00:04:50,060 --> 00:04:46,770 they used two criteria to judge the 121 00:04:51,640 --> 00:04:50,070 presence of a protein or a gene in the 122 00:04:54,980 --> 00:04:51,650 common ancestor of archaea and bacteria 123 00:04:56,570 --> 00:04:54,990 one the present should be the protein or 124 00:04:58,970 --> 00:04:56,580 the gene should be present in at least 125 00:05:00,980 --> 00:04:58,980 two higher taxonomic groups and I'll 126 00:05:03,440 --> 00:05:00,990 describe what that means in a second of 127 00:05:05,000 --> 00:05:03,450 each bacteria and archaea and the second 128 00:05:07,940 --> 00:05:05,010 is that if you draw a phylogenetic tree 129 00:05:10,100 --> 00:05:07,950 of this protein individually it should 130 00:05:12,680 --> 00:05:10,110 split the archaea in the bacteria just 131 00:05:15,200 --> 00:05:12,690 like a ribosomal or an elongation factor 132 00:05:17,660 --> 00:05:15,210 gene would so what what do they mean by 133 00:05:19,870 --> 00:05:17,670 that they mean something like this here 134 00:05:22,460 --> 00:05:19,880 on the left are a bacteria in blue and 135 00:05:24,500 --> 00:05:22,470 if you squint your eyes or if you've got 136 00:05:26,630 --> 00:05:24,510 good eyes you can see that there are two 137 00:05:28,820 --> 00:05:26,640 dark blue lines on the bacterial tree 138 00:05:31,340 --> 00:05:28,830 this would be representing that a 139 00:05:33,590 --> 00:05:31,350 protein or a gene is present in two 140 00:05:35,180 --> 00:05:33,600 higher taxes of bacteria and on the 141 00:05:36,890 --> 00:05:35,190 right we've got this other group of 142 00:05:38,870 --> 00:05:36,900 organisms that we call the archaea and 143 00:05:40,070 --> 00:05:38,880 if you look closely there's two dark red 144 00:05:43,160 --> 00:05:40,080 lines and this would be indicative of 145 00:05:45,440 --> 00:05:43,170 two of these genes being present in 146 00:05:47,060 --> 00:05:45,450 archaea and if you found a protein that 147 00:05:49,220 --> 00:05:47,070 looked like this according to these 148 00:05:50,540 --> 00:05:49,230 criteria you would conclude okay this 149 00:05:52,400 --> 00:05:50,550 this is a good candidate for something 150 00:05:55,160 --> 00:05:52,410 that was present in the last Universal 151 00:05:57,380 --> 00:05:55,170 Universal common ancestor or as I like 152 00:06:00,650 --> 00:05:57,390 to call just the last common ancestor of 153 00:06:02,360 --> 00:06:00,660 bacteria and archaea and in the paper 154 00:06:04,790 --> 00:06:02,370 they're thinking about hydrothermal 155 00:06:08,180 --> 00:06:04,800 vents and they come up with this scheme 156 00:06:10,010 --> 00:06:08,190 and when I was reading this paper it 157 00:06:12,500 --> 00:06:10,020 really caught my eye because they 158 00:06:14,900 --> 00:06:12,510 included a nitrogenous and also radical 159 00:06:16,580 --> 00:06:14,910 Sam proteins inside of those and those 160 00:06:18,890 --> 00:06:16,590 are these proteins here and I just want 161 00:06:20,780 --> 00:06:18,900 to discuss briefly what the phylogeny of 162 00:06:23,330 --> 00:06:20,790 those proteins looks like and whether or 163 00:06:25,790 --> 00:06:23,340 not this is a valid conclusion to 164 00:06:27,560 --> 00:06:25,800 include in their data set what is a 165 00:06:30,740 --> 00:06:27,570 nitrogenous and what is a radical Sam 166 00:06:33,080 --> 00:06:30,750 protein a nitrogenous is the only known 167 00:06:34,730 --> 00:06:33,090 biological catalyst that can take n2 168 00:06:36,500 --> 00:06:34,740 from the atmosphere and turn it into 169 00:06:37,970 --> 00:06:36,510 ammonium and so this is this vertical 170 00:06:41,390 --> 00:06:37,980 reaction on the left here where you take 171 00:06:43,100 --> 00:06:41,400 nitrogen gas plus six electrons you you 172 00:06:45,350 --> 00:06:43,110 spill off a couple electrons on the 173 00:06:46,460 --> 00:06:45,360 hydrogen that the enzyme can't hold on 174 00:06:48,890 --> 00:06:46,470 to the electrons and so you always make 175 00:06:52,840 --> 00:06:48,900 a little bit of hydrogen you have to 176 00:06:56,600 --> 00:06:52,850 push the reaction forward with ATP and 177 00:06:58,820 --> 00:06:56,610 this is a this is a phylogenetic tree 178 00:07:00,890 --> 00:06:58,830 of the actual catalytic subunit of the 179 00:07:02,689 --> 00:07:00,900 protein that's drawn on the left and so 180 00:07:04,339 --> 00:07:02,699 what we would like to ask ourselves at 181 00:07:05,839 --> 00:07:04,349 this stage is where are the Archaea 182 00:07:07,399 --> 00:07:05,849 industry and where are the bacteria does 183 00:07:09,589 --> 00:07:07,409 it recover the archaea bacteria split 184 00:07:11,809 --> 00:07:09,599 and is it present in two higher taxes of 185 00:07:14,510 --> 00:07:11,819 each of these same question we can ask 186 00:07:17,029 --> 00:07:14,520 for this radical Sam protein family 187 00:07:18,559 --> 00:07:17,039 radical Sam protein family they all 188 00:07:21,040 --> 00:07:18,569 carry out the reaction shown on the 189 00:07:24,830 --> 00:07:21,050 right they take s-adenosylmethionine 190 00:07:27,409 --> 00:07:24,840 which is a cool sulfonium ion and they 191 00:07:29,300 --> 00:07:27,419 donate a single electron from an iron 192 00:07:30,800 --> 00:07:29,310 sulfur cluster on to that sulfonium ion 193 00:07:32,779 --> 00:07:30,810 and then they make this deoxyadenosine 194 00:07:34,909 --> 00:07:32,789 radical that you see on the right and 195 00:07:36,920 --> 00:07:34,919 that deoxyadenosine radical can go on 196 00:07:39,439 --> 00:07:36,930 and do almost any chemical reaction that 197 00:07:43,129 --> 00:07:39,449 you want to dream up it's wonderfully an 198 00:07:46,070 --> 00:07:43,139 amazing lead diverse chemical chemically 199 00:07:47,300 --> 00:07:46,080 reactive enzyme it's found all over the 200 00:07:49,369 --> 00:07:47,310 place in biology it's probably it 201 00:07:51,499 --> 00:07:49,379 probably is a good candidate to include 202 00:07:54,679 --> 00:07:51,509 in toluca but what does what does the 203 00:07:56,330 --> 00:07:54,689 phylogeny look like so I want to just 204 00:07:59,300 --> 00:07:56,340 talk about those two protein families 205 00:08:01,640 --> 00:07:59,310 today first the nitrogenase is it 206 00:08:02,809 --> 00:08:01,650 present in two acts to higher taxes of 207 00:08:05,480 --> 00:08:02,819 archaea and bacteria 208 00:08:08,059 --> 00:08:05,490 well actually the nitrogenase is only 209 00:08:10,550 --> 00:08:08,069 present it's restricted to a sub group 210 00:08:13,369 --> 00:08:10,560 in in a in one particular phyla of 211 00:08:15,079 --> 00:08:13,379 archaea so it's actually well restricted 212 00:08:17,480 --> 00:08:15,089 within the archaea it's only present in 213 00:08:18,890 --> 00:08:17,490 methanogenic archaea which is surprising 214 00:08:21,350 --> 00:08:18,900 it's actually surprising that it's not 215 00:08:23,240 --> 00:08:21,360 distributed more widely again it's the 216 00:08:24,740 --> 00:08:23,250 only known biological catalyst to take 217 00:08:26,929 --> 00:08:24,750 nitrogen from the atmosphere and put it 218 00:08:28,850 --> 00:08:26,939 into biomass should be awesome to have 219 00:08:31,730 --> 00:08:28,860 this in your genome it's only present in 220 00:08:33,800 --> 00:08:31,740 meth an agenda query archaea as far as 221 00:08:36,259 --> 00:08:33,810 we know what our sequence is today let's 222 00:08:38,509 --> 00:08:36,269 take a look at the nitrogenous and ask 223 00:08:40,880 --> 00:08:38,519 ourselves where the archaea and the 224 00:08:43,100 --> 00:08:40,890 bacteria branch within one of these 225 00:08:45,769 --> 00:08:43,110 trees here I've colored all of the 226 00:08:47,660 --> 00:08:45,779 archaeal sequences in red and since it's 227 00:08:50,750 --> 00:08:47,670 kind of hard to see I just put a little 228 00:08:52,460 --> 00:08:50,760 orange arrow on those sequences and see 229 00:08:54,170 --> 00:08:52,470 you can see that the archaea branch 230 00:08:55,790 --> 00:08:54,180 super super polyfill ethically within 231 00:08:57,920 --> 00:08:55,800 this and this doesn't look a lot like 232 00:09:01,850 --> 00:08:57,930 this tree on the left where the bacteria 233 00:09:03,170 --> 00:09:01,860 and the Archaea are split and they that 234 00:09:04,699 --> 00:09:03,180 leads us to call them archaea and 235 00:09:06,620 --> 00:09:04,709 bacteria and give them the the 236 00:09:07,819 --> 00:09:06,630 designation of different domains the 237 00:09:09,920 --> 00:09:07,829 nitrogenous tree doesn't look like that 238 00:09:10,370 --> 00:09:09,930 so what I want to suggest to you is that 239 00:09:12,350 --> 00:09:10,380 based on 240 00:09:15,080 --> 00:09:12,360 the author's criteria that this is not a 241 00:09:17,090 --> 00:09:15,090 candidate to put into the last common 242 00:09:20,330 --> 00:09:17,100 ancestor of archaea and bacteria so I'll 243 00:09:22,160 --> 00:09:20,340 put an X through that and briefly I want 244 00:09:24,650 --> 00:09:22,170 to run through this radical Sam protein 245 00:09:26,750 --> 00:09:24,660 family is it present in all sorts of 246 00:09:29,120 --> 00:09:26,760 archaea and all sorts of bacteria it is 247 00:09:31,760 --> 00:09:29,130 it's a super super widely used enzyme 248 00:09:33,650 --> 00:09:31,770 family it's it's a pretty simple protein 249 00:09:35,900 --> 00:09:33,660 fold it binds an iron sulfur cluster it 250 00:09:37,430 --> 00:09:35,910 uses this common substrate it generates 251 00:09:38,990 --> 00:09:37,440 a radical mechanism and then that 252 00:09:41,720 --> 00:09:39,000 radical can go off and do all sorts of 253 00:09:43,520 --> 00:09:41,730 nice things for the cell but if you look 254 00:09:45,770 --> 00:09:43,530 at a phylogeny of it again you see that 255 00:09:48,620 --> 00:09:45,780 the archaea split up the bacterial 256 00:09:50,570 --> 00:09:48,630 distribution a lot there's a lot more 257 00:09:52,730 --> 00:09:50,580 black lines on this plot and also on the 258 00:09:54,200 --> 00:09:52,740 previous plot but this is because this 259 00:09:55,700 --> 00:09:54,210 is a sequence artifact because we don't 260 00:09:58,730 --> 00:09:55,710 have enough archaeal genomes right now 261 00:10:00,200 --> 00:09:58,740 however regardless of that you can see 262 00:10:05,630 --> 00:10:00,210 that it does not recover the archaea 263 00:10:08,120 --> 00:10:05,640 bacteria split and therefore I'd like to 264 00:10:13,220 --> 00:10:08,130 suggest that we cross this off of the 265 00:10:15,050 --> 00:10:13,230 list and so I want to use this kind of 266 00:10:18,230 --> 00:10:15,060 as fodder to get you to come to the very 267 00:10:21,050 --> 00:10:18,240 last session of the symposium the after 268 00:10:23,990 --> 00:10:21,060 shop that I'll be chairing on Tuesday 269 00:10:25,820 --> 00:10:24,000 where we're going to be discussing what 270 00:10:30,440 --> 00:10:25,830 are the ways that we can safely and 271 00:10:32,600 --> 00:10:30,450 justifiably discuss ancestral States of 272 00:10:34,550 --> 00:10:32,610 organisms this doesn't have to be all 273 00:10:36,260 --> 00:10:34,560 the way back at the very origination of 274 00:10:39,410 --> 00:10:36,270 life or the origination origination of 275 00:10:40,580 --> 00:10:39,420 cells but I'd like us to be able to get 276 00:10:41,990 --> 00:10:40,590 together and talk about what are the 277 00:10:43,400 --> 00:10:42,000 criteria that we can safely use to 278 00:10:47,350 --> 00:10:43,410 evaluate whether or not something was 279 00:10:50,090 --> 00:10:47,360 present in an ancestor of a group and 280 00:10:54,860 --> 00:10:50,100 when we might not be justified to do 281 00:10:56,870 --> 00:10:54,870 that I'm not a vulgar guy but I'll put 282 00:10:59,060 --> 00:10:56,880 this up because it was funny I'm not 283 00:11:01,400 --> 00:10:59,070 trying to trash any any work right here 284 00:11:04,730 --> 00:11:01,410 I'm actually just trying to be 285 00:11:06,650 --> 00:11:04,740 constructive this this editorial is 286 00:11:09,920 --> 00:11:06,660 actually really really nice and and the 287 00:11:11,690 --> 00:11:09,930 editor talks about what it's like to be 288 00:11:13,100 --> 00:11:11,700 an editor and get all these nice reviews 289 00:11:14,840 --> 00:11:13,110 or sometimes mean reviews and what you 290 00:11:15,800 --> 00:11:14,850 should do as an author about that but I 291 00:11:17,420 --> 00:11:15,810 just want to make the point that I'm not 292 00:11:19,670 --> 00:11:17,430 trying to trash anything because I know 293 00:11:21,350 --> 00:11:19,680 that's easy to do I'm trying with 294 00:11:23,060 --> 00:11:21,360 everybody here to put together these 295 00:11:23,990 --> 00:11:23,070 different puzzle pieces and try to find 296 00:11:27,260 --> 00:11:24,000 some robust 297 00:11:30,020 --> 00:11:27,270 conclusions so back to my main topic 298 00:11:31,130 --> 00:11:30,030 here kind of asking this question what 299 00:11:33,800 --> 00:11:31,140 are the ways that the first cells 300 00:11:36,620 --> 00:11:33,810 conserve energy how did they take 301 00:11:38,240 --> 00:11:36,630 chemical act chemical reactions use 302 00:11:40,430 --> 00:11:38,250 chemical potentials that exist in the 303 00:11:42,740 --> 00:11:40,440 environment and save it temporarily so 304 00:11:44,780 --> 00:11:42,750 that they can order their cells how can 305 00:11:48,500 --> 00:11:44,790 they maintain themselves and then also 306 00:11:49,910 --> 00:11:48,510 reproduce and so I said to get everybody 307 00:11:51,860 --> 00:11:49,920 on the same page of this concept of 308 00:11:54,800 --> 00:11:51,870 energy conservation I would go to a very 309 00:11:56,570 --> 00:11:54,810 basic level and I will I'll take you 310 00:11:58,640 --> 00:11:56,580 guys to my freshmen in biology class 311 00:11:59,930 --> 00:11:58,650 where I start to talk about energy 312 00:12:02,390 --> 00:11:59,940 conservation and this isn't a perfect 313 00:12:03,830 --> 00:12:02,400 analogy but it's it's reasonable let's 314 00:12:06,590 --> 00:12:03,840 take a look at the left and if you drop 315 00:12:08,000 --> 00:12:06,600 a rock off of a cliff you can take 316 00:12:10,220 --> 00:12:08,010 potential energy and convert it into 317 00:12:11,680 --> 00:12:10,230 kinetic energy and then when it hits the 318 00:12:14,270 --> 00:12:11,690 ground it turns into heat and noise 319 00:12:16,100 --> 00:12:14,280 energy now you can save some of that 320 00:12:18,710 --> 00:12:16,110 energy when the rock drops you can put 321 00:12:20,630 --> 00:12:18,720 like a little rock windmill in there and 322 00:12:22,760 --> 00:12:20,640 then you can use that rock with no later 323 00:12:26,930 --> 00:12:22,770 on to do some work and this is kind of 324 00:12:29,480 --> 00:12:26,940 what biology does so let's get ready for 325 00:12:31,340 --> 00:12:29,490 a few molecules here this is kind of 326 00:12:33,980 --> 00:12:31,350 what biology does here here's the 327 00:12:35,570 --> 00:12:33,990 pathway of glycolysis in the middle up 328 00:12:37,760 --> 00:12:35,580 here there's a blurry molecule of 329 00:12:40,300 --> 00:12:37,770 glucose that's kind of the rock that's 330 00:12:42,530 --> 00:12:40,310 on top of the cliff it doesn't have any 331 00:12:44,840 --> 00:12:42,540 potential energy due to gravity at all 332 00:12:46,280 --> 00:12:44,850 but it does have potential energy in the 333 00:12:48,860 --> 00:12:46,290 form of chemical energy as you go to 334 00:12:51,290 --> 00:12:48,870 pyruvate and lactate and as it drops 335 00:12:53,720 --> 00:12:51,300 energetically what life is able to do is 336 00:12:56,600 --> 00:12:53,730 save some of that energy off on the left 337 00:12:58,340 --> 00:12:56,610 and that's by turning a little crank 338 00:13:01,400 --> 00:12:58,350 it's not really a gear it's an enzyme 339 00:13:03,890 --> 00:13:01,410 that smashes together phosphate and ATP 340 00:13:06,680 --> 00:13:03,900 and it makes ATP and so this is the way 341 00:13:08,960 --> 00:13:06,690 that life saves or conserves energy by 342 00:13:10,760 --> 00:13:08,970 substrate level phosphorylation now 343 00:13:13,130 --> 00:13:10,770 there are three ways that biology is 344 00:13:15,680 --> 00:13:13,140 known to save energy one is by using 345 00:13:18,650 --> 00:13:15,690 this process here either in glycolysis 346 00:13:19,880 --> 00:13:18,660 or some other set of reactions but they 347 00:13:21,740 --> 00:13:19,890 all have in common that they take a 348 00:13:23,840 --> 00:13:21,750 phosphate group in the and they put it 349 00:13:25,670 --> 00:13:23,850 onto another phosphate group and that 350 00:13:28,040 --> 00:13:25,680 gives them kind of a little molecular 351 00:13:29,750 --> 00:13:28,050 spring to drive reactions with and also 352 00:13:32,300 --> 00:13:29,760 sometimes people people discuss it as 353 00:13:33,800 --> 00:13:32,310 some dehydration powder because you're 354 00:13:35,930 --> 00:13:33,810 actually losing a water molecule when 355 00:13:37,879 --> 00:13:35,940 you put two phosphates together and so 356 00:13:40,460 --> 00:13:37,889 life saves this ATP and that's what 357 00:13:42,169 --> 00:13:40,470 we often call like the energy currency 358 00:13:43,609 --> 00:13:42,179 of life it doesn't necessarily have to 359 00:13:45,679 --> 00:13:43,619 be like that but it seems like that's 360 00:13:47,509 --> 00:13:45,689 what it uses today and again this is 361 00:13:48,499 --> 00:13:47,519 this concept of fuss substrate level 362 00:13:50,509 --> 00:13:48,509 phosphorylation 363 00:13:51,919 --> 00:13:50,519 let's compare dropping a rock off the 364 00:13:54,009 --> 00:13:51,929 cliff and having it go through a rock 365 00:13:56,929 --> 00:13:54,019 windmill and lifting it lifting a bucket 366 00:13:59,179 --> 00:13:56,939 to this you're taking a different form 367 00:14:01,009 --> 00:13:59,189 of energy but you're saving it in one 368 00:14:02,449 --> 00:14:01,019 case you're saving it with a bucket that 369 00:14:04,639 --> 00:14:02,459 you lift up and in this case you're 370 00:14:06,590 --> 00:14:04,649 saving it in a form another form of 371 00:14:09,139 --> 00:14:06,600 chemical energy and so what life is 372 00:14:11,629 --> 00:14:09,149 doing across all the diversity of life 373 00:14:14,119 --> 00:14:11,639 is taking different types of rocks ie 374 00:14:15,859 --> 00:14:14,129 metabolites and changing them all into a 375 00:14:17,239 --> 00:14:15,869 common currency ATP and that's very 376 00:14:18,650 --> 00:14:17,249 useful for the cell because then it can 377 00:14:21,049 --> 00:14:18,660 go and drive multiple different 378 00:14:23,090 --> 00:14:21,059 reactions with various chemical 379 00:14:26,150 --> 00:14:23,100 potentials so this is the concept of 380 00:14:29,299 --> 00:14:26,160 substrate level phosphorylation the 381 00:14:30,769 --> 00:14:29,309 other mechanism of energy conservation 382 00:14:33,619 --> 00:14:30,779 that I want to talk to you about today 383 00:14:36,369 --> 00:14:33,629 is the concept that was introduced to us 384 00:14:40,369 --> 00:14:36,379 by Mitchell energy conservation by 385 00:14:42,919 --> 00:14:40,379 chemiosmosis and so in this case the 386 00:14:46,609 --> 00:14:42,929 rock the chemical potential that's there 387 00:14:49,429 --> 00:14:46,619 is shown as electrons over here on the 388 00:14:51,650 --> 00:14:49,439 left in blue that are at a reduced 389 00:14:54,019 --> 00:14:51,660 potential and as they moved to a more 390 00:14:57,429 --> 00:14:54,029 oxidized potential onto something like 391 00:14:59,749 --> 00:14:57,439 oxygen or nitrate or manganese that 392 00:15:02,299 --> 00:14:59,759 energy release can be used to do some 393 00:15:04,549 --> 00:15:02,309 work this time it's not done in the way 394 00:15:07,519 --> 00:15:04,559 of putting two phosphates together it's 395 00:15:09,819 --> 00:15:07,529 done by extruding protons across the 396 00:15:12,949 --> 00:15:09,829 membrane and so this is an actual pump 397 00:15:15,319 --> 00:15:12,959 and so we can get by using analogies 398 00:15:17,150 --> 00:15:15,329 about machines in this stage because the 399 00:15:19,669 --> 00:15:17,160 what the protein is actually doing here 400 00:15:21,650 --> 00:15:19,679 is as an electron moves through it to 401 00:15:27,759 --> 00:15:21,660 one of these acceptors the protein is 402 00:15:29,929 --> 00:15:27,769 saving it's conserving energy by having 403 00:15:31,369 --> 00:15:29,939 conformational changes occur through the 404 00:15:33,229 --> 00:15:31,379 protein and it's actually squeezing out 405 00:15:35,150 --> 00:15:33,239 a proton from the inside to the outside 406 00:15:36,710 --> 00:15:35,160 and if the cell does that a bunch of 407 00:15:38,449 --> 00:15:36,720 times you can get a bunch of these 408 00:15:39,919 --> 00:15:38,459 yellow protons on the outside of the 409 00:15:44,299 --> 00:15:39,929 cell and then later on you can use 410 00:15:46,220 --> 00:15:44,309 another machine to allow that chemical 411 00:15:48,139 --> 00:15:46,230 potential when it gets dissipated to put 412 00:15:49,369 --> 00:15:48,149 two phosphates together its substrate 413 00:15:51,650 --> 00:15:49,379 level phosphorylation but it's 414 00:15:53,720 --> 00:15:51,660 accomplished by utilizing 415 00:15:55,400 --> 00:15:53,730 chemical chemical energy in the form of 416 00:15:57,560 --> 00:15:55,410 a membrane-spanning ion potential and 417 00:15:59,750 --> 00:15:57,570 that's what we call chemiosmosis this is 418 00:16:01,370 --> 00:15:59,760 the second out of three ways that we 419 00:16:02,990 --> 00:16:01,380 know biology works today 420 00:16:03,980 --> 00:16:03,000 it's remarkable there's only three ways 421 00:16:05,510 --> 00:16:03,990 one is substrate level phosphorylation 422 00:16:08,210 --> 00:16:05,520 and one is substrate level 423 00:16:09,380 --> 00:16:08,220 phosphorylation coupled chemiosmosis the 424 00:16:11,030 --> 00:16:09,390 other one has to do with electron 425 00:16:15,320 --> 00:16:11,040 transfer and I don't have time to talk 426 00:16:19,280 --> 00:16:15,330 about it today but I want us to ask what 427 00:16:21,800 --> 00:16:19,290 what is the way that the first cell or 428 00:16:24,380 --> 00:16:21,810 if we go liberally the first non 429 00:16:26,210 --> 00:16:24,390 compartmentalized form of life used to 430 00:16:30,530 --> 00:16:26,220 take chemical potentials and turn them 431 00:16:34,520 --> 00:16:30,540 in them into a common set of molecules 432 00:16:36,320 --> 00:16:34,530 that it can drive a metabolism with was 433 00:16:37,790 --> 00:16:36,330 it substrate level phosphorylation or 434 00:16:39,400 --> 00:16:37,800 was it chemiosmosis or was it something 435 00:16:41,990 --> 00:16:39,410 else it might be something else 436 00:16:44,960 --> 00:16:42,000 let's delve a little bit deeper into 437 00:16:48,380 --> 00:16:44,970 this chemiosmosis topic because many 438 00:16:49,910 --> 00:16:48,390 people have said or at least some people 439 00:16:53,000 --> 00:16:49,920 that I apparently listen to and call 440 00:16:55,130 --> 00:16:53,010 many have said that chemiosmosis is the 441 00:16:57,680 --> 00:16:55,140 primordial feature of cells also let's 442 00:17:00,260 --> 00:16:57,690 do this so therefore the first cell does 443 00:17:02,240 --> 00:17:00,270 that I showed you one possible way of 444 00:17:04,670 --> 00:17:02,250 generating at chemiosmotic potential but 445 00:17:06,290 --> 00:17:04,680 I'd like to remind everybody or 446 00:17:08,090 --> 00:17:06,300 introduce you to the topic that there 447 00:17:10,310 --> 00:17:08,100 are a number of different ways of 448 00:17:13,130 --> 00:17:10,320 generating chem up chemical chemiosmotic 449 00:17:15,020 --> 00:17:13,140 potentials in a cell and basically we 450 00:17:17,900 --> 00:17:15,030 can break it down into two two things 451 00:17:19,700 --> 00:17:17,910 one is you remove positive charge from 452 00:17:21,320 --> 00:17:19,710 the cell that's what that proton pump 453 00:17:22,850 --> 00:17:21,330 was doing it was taking a positive ion 454 00:17:25,070 --> 00:17:22,860 and it was shoving it outside of the 455 00:17:26,480 --> 00:17:25,080 cell and that results in the outside 456 00:17:28,970 --> 00:17:26,490 being more positive in the inside being 457 00:17:30,620 --> 00:17:28,980 more negative or the other way to do 458 00:17:32,900 --> 00:17:30,630 this is to put negative charge inside of 459 00:17:35,110 --> 00:17:32,910 this cell so the same thing happens the 460 00:17:37,760 --> 00:17:35,120 inside of the cell becomes more negative 461 00:17:40,100 --> 00:17:37,770 than the outside and life is known to 462 00:17:42,890 --> 00:17:40,110 operate in both of these different ways 463 00:17:45,560 --> 00:17:42,900 at these general classes and so what are 464 00:17:47,630 --> 00:17:45,570 what would be a way that the first form 465 00:17:50,780 --> 00:17:47,640 of life could could accomplish something 466 00:17:55,760 --> 00:17:50,790 like this if that's indeed what what it 467 00:17:57,590 --> 00:17:55,770 was doing oftentimes methanogens and 468 00:18:00,740 --> 00:17:57,600 heceta genes which I mentioned in my 469 00:18:02,720 --> 00:18:00,750 abstract are introduced as possible 470 00:18:04,430 --> 00:18:02,730 organisms that would have accomplished 471 00:18:05,480 --> 00:18:04,440 this in a way that was similar to the 472 00:18:07,700 --> 00:18:05,490 first cells 473 00:18:09,830 --> 00:18:07,710 and people suggest this because they 474 00:18:12,110 --> 00:18:09,840 look a little bit simple it looks like 475 00:18:13,970 --> 00:18:12,120 you can just take co2 on the top and 476 00:18:16,250 --> 00:18:13,980 deliver electrons in the form of 477 00:18:19,970 --> 00:18:16,260 hydrogen hydrogen gas and make methane 478 00:18:21,890 --> 00:18:19,980 and you can run two pumps and make a 479 00:18:26,450 --> 00:18:21,900 chemiosmotic potential and everything's 480 00:18:28,370 --> 00:18:26,460 great these pumps though are are quite 481 00:18:30,530 --> 00:18:28,380 complicated I like to suggest to you and 482 00:18:32,510 --> 00:18:30,540 that's why I listed the the number of 483 00:18:35,270 --> 00:18:32,520 protein subunits that comprises each 484 00:18:37,010 --> 00:18:35,280 pump remember what these these pumps are 485 00:18:39,980 --> 00:18:37,020 doing is taking one form of chemical 486 00:18:42,260 --> 00:18:39,990 energy and and actually using that 487 00:18:43,910 --> 00:18:42,270 chemical energy to perform 488 00:18:45,919 --> 00:18:43,920 conformational changes in the protein 489 00:18:48,860 --> 00:18:45,929 and actually squeeze ions out of the 490 00:18:51,860 --> 00:18:48,870 membrane and it takes biology at least 491 00:18:53,750 --> 00:18:51,870 eight or nine individual peptide 492 00:18:55,460 --> 00:18:53,760 subunits to come together and exactly 493 00:18:58,190 --> 00:18:55,470 the right way to do this so I I think 494 00:19:00,950 --> 00:18:58,200 this is quite a complicated mechanism 495 00:19:05,360 --> 00:19:00,960 that we have here let's look at se 496 00:19:08,330 --> 00:19:05,370 doujins which are often times thought to 497 00:19:10,250 --> 00:19:08,340 also be simple they do a metabolism that 498 00:19:11,780 --> 00:19:10,260 looks a lot like methanogenesis except 499 00:19:14,690 --> 00:19:11,790 for its branched instead of making 500 00:19:16,850 --> 00:19:14,700 methane they make acetate and again they 501 00:19:17,960 --> 00:19:16,860 can exist with only two pumps inside of 502 00:19:20,600 --> 00:19:17,970 them two they use a different variety 503 00:19:22,490 --> 00:19:20,610 it's called R and F it happens to be 504 00:19:24,440 --> 00:19:22,500 able to run with six protein subunits so 505 00:19:25,160 --> 00:19:24,450 it looks a little bit simpler again a 506 00:19:28,220 --> 00:19:25,170 TPAs 507 00:19:32,169 --> 00:19:28,230 actually has to use nine different 508 00:19:34,549 --> 00:19:32,179 subunits it's pretty complicated so i I 509 00:19:36,049 --> 00:19:34,559 when I learned this I thought oh this is 510 00:19:38,299 --> 00:19:36,059 really really too hard for the first 511 00:19:40,730 --> 00:19:38,309 types of cells to learn and I started 512 00:19:44,330 --> 00:19:40,740 looking for other ways that life might 513 00:19:46,310 --> 00:19:44,340 be able to conserve energy and I'll 514 00:19:50,600 --> 00:19:46,320 introduce that topic to you but before I 515 00:19:52,280 --> 00:19:50,610 do I just want to go a little bit deeper 516 00:19:53,840 --> 00:19:52,290 into these diagrams these diagrams are 517 00:19:57,740 --> 00:19:53,850 kind of complicated there's a lot of 518 00:20:00,860 --> 00:19:57,750 arrows but this chemiosmotic nature of 519 00:20:02,930 --> 00:20:00,870 these cells here results in a really 520 00:20:04,549 --> 00:20:02,940 really remarkable similarity and that 521 00:20:06,770 --> 00:20:04,559 remarkable similarity goes right to the 522 00:20:08,860 --> 00:20:06,780 heart of chemiosmotic potential that 523 00:20:12,049 --> 00:20:08,870 similarity comes can be viewed in this 524 00:20:14,659 --> 00:20:12,059 slanted graph here that Steve's inter 525 00:20:17,000 --> 00:20:14,669 plotted in 1993 whereas he's plotting 526 00:20:19,100 --> 00:20:17,010 the chemical potential of the energy of 527 00:20:20,870 --> 00:20:19,110 the metabolism making methane or making 528 00:20:23,539 --> 00:20:20,880 acetate as a function of the hydrogen 529 00:20:26,780 --> 00:20:23,549 partial pressure how many what's the 530 00:20:28,250 --> 00:20:26,790 electron availability and how reducing 531 00:20:32,060 --> 00:20:28,260 is the solution to drive the reaction 532 00:20:34,610 --> 00:20:32,070 and where does the metabolism stop it 533 00:20:36,620 --> 00:20:34,620 turns out that both of these see where 534 00:20:41,110 --> 00:20:36,630 my cursor here is both of these things 535 00:20:44,870 --> 00:20:41,120 stop right around 30 kilojoules per mole 536 00:20:47,570 --> 00:20:44,880 of chemical reaction energy that is you 537 00:20:49,310 --> 00:20:47,580 can take a methanogens or a Necedah Jen 538 00:20:50,810 --> 00:20:49,320 which looks similar but they actually 539 00:20:52,820 --> 00:20:50,820 have different chemiosmotic pumping 540 00:20:54,740 --> 00:20:52,830 units you can stick them in a roomful of 541 00:20:57,289 --> 00:20:54,750 hydrogen and they will consume the 542 00:21:00,110 --> 00:20:57,299 hydrogen all the way until there's only 543 00:21:02,450 --> 00:21:00,120 enough to result in a Gibbs free energy 544 00:21:09,110 --> 00:21:02,460 of the reaction to be around 30 545 00:21:10,909 --> 00:21:09,120 kilojoules per mole so this I think is a 546 00:21:12,710 --> 00:21:10,919 product of the chemiosmotic potential 547 00:21:14,810 --> 00:21:12,720 and how how much energy it actually 548 00:21:15,289 --> 00:21:14,820 takes to pump a single ion across the 549 00:21:18,289 --> 00:21:15,299 membrane 550 00:21:20,690 --> 00:21:18,299 so this metabolism is driven by hydrogen 551 00:21:22,820 --> 00:21:20,700 gas combining on to co2 and eventually 552 00:21:24,799 --> 00:21:22,830 making methane how much energy does it 553 00:21:26,600 --> 00:21:24,809 take to do that or what's the 554 00:21:28,250 --> 00:21:26,610 concentration of hydrogen that it takes 555 00:21:29,750 --> 00:21:28,260 to do that the concentration to do that 556 00:21:33,169 --> 00:21:29,760 and make it throw my dynamically 557 00:21:35,659 --> 00:21:33,179 favorable is extremely low however to 558 00:21:37,310 --> 00:21:35,669 conserve energy or to save energy during 559 00:21:39,460 --> 00:21:37,320 the process you actually have to have 560 00:21:42,470 --> 00:21:39,470 enough to pump at least a single ion and 561 00:21:44,360 --> 00:21:42,480 that's probably why both methanogens and 562 00:21:47,210 --> 00:21:44,370 a/c didn't stop at the same chemical 563 00:21:49,090 --> 00:21:47,220 potential but because they have one 564 00:21:51,470 --> 00:21:49,100 makes methane and one makes acetate 565 00:21:55,630 --> 00:21:51,480 methanogens can always out-compete 566 00:21:57,650 --> 00:21:55,640 heceta jones for hydrogen so because of 567 00:21:59,600 --> 00:21:57,660 not because of the chemiosmotic 568 00:22:01,549 --> 00:21:59,610 potential but because simply because one 569 00:22:02,720 --> 00:22:01,559 makes methane and one makes acetate what 570 00:22:04,039 --> 00:22:02,730 we're seeing here is a profound 571 00:22:05,630 --> 00:22:04,049 ecological difference between 572 00:22:07,460 --> 00:22:05,640 methanogens and asita jhin's and it's 573 00:22:10,669 --> 00:22:07,470 all coming down to how much how much 574 00:22:16,610 --> 00:22:10,679 energy it takes to to push and on across 575 00:22:18,260 --> 00:22:16,620 them the membrane back to this question 576 00:22:20,330 --> 00:22:18,270 of complexity and whether or not any of 577 00:22:22,850 --> 00:22:20,340 this is relevant our consideration of 578 00:22:24,710 --> 00:22:22,860 the first cells I said that the ATP aise 579 00:22:27,590 --> 00:22:24,720 takes at least nine different protein 580 00:22:31,159 --> 00:22:27,600 subunits to function it does and here's 581 00:22:32,750 --> 00:22:31,169 a picture of it which now that I look at 582 00:22:33,860 --> 00:22:32,760 it I realize I haven't counted 583 00:22:36,200 --> 00:22:33,870 so it looks like it's actually really 584 00:22:37,820 --> 00:22:36,210 complicated but that's that there's a 585 00:22:40,760 --> 00:22:37,830 lot of those L copies in there but we 586 00:22:42,620 --> 00:22:40,770 could count those as one here it is this 587 00:22:44,540 --> 00:22:42,630 is a cartoon diagram but it's it's very 588 00:22:46,460 --> 00:22:44,550 complicated the way it works is that 589 00:22:48,860 --> 00:22:46,470 it's actually spinning around in there 590 00:22:51,020 --> 00:22:48,870 and as it's spinning around it can bind 591 00:22:54,020 --> 00:22:51,030 ADP and phosphate and move them together 592 00:22:57,110 --> 00:22:54,030 it operates kind of like a von Kalenjin 593 00:22:59,780 --> 00:22:57,120 if any of you are Mazda aficionados and 594 00:23:02,620 --> 00:22:59,790 you know about the rx-7 it operates kind 595 00:23:08,870 --> 00:23:07,430 we can talk cars later so you've got 596 00:23:10,790 --> 00:23:08,880 something that operates and you can 597 00:23:12,950 --> 00:23:10,800 compare it to a funcle' engine and 598 00:23:14,450 --> 00:23:12,960 people have because it works in these 599 00:23:18,080 --> 00:23:14,460 three different cycles with these lobes 600 00:23:20,030 --> 00:23:18,090 and we can ask ourselves how can we ever 601 00:23:21,410 --> 00:23:20,040 think about the first cells existing 602 00:23:24,080 --> 00:23:21,420 with a membrane and having a protein 603 00:23:25,460 --> 00:23:24,090 complex like this embedded in it and I 604 00:23:28,250 --> 00:23:25,470 don't know how to do that I think this 605 00:23:31,160 --> 00:23:28,260 is a really big problem for us and what 606 00:23:32,750 --> 00:23:31,170 I what I want to consider with you and 607 00:23:35,060 --> 00:23:32,760 I'm gonna welcome your comments here in 608 00:23:37,010 --> 00:23:35,070 a few moments is what what are the ways 609 00:23:38,990 --> 00:23:37,020 that earlier energy conservation could 610 00:23:40,400 --> 00:23:39,000 have been operative here what I've done 611 00:23:43,730 --> 00:23:40,410 on the right here in this little table 612 00:23:47,360 --> 00:23:43,740 is just taken kind of a little bucket 613 00:23:49,190 --> 00:23:47,370 list of early or simple protein 614 00:23:51,230 --> 00:23:49,200 complexes that are able to conserve 615 00:23:54,860 --> 00:23:51,240 energy with a chemiosmotic potential and 616 00:23:56,570 --> 00:23:54,870 just for simplicity for us to quickly 617 00:23:59,030 --> 00:23:56,580 judge the level of complexity that we're 618 00:24:01,310 --> 00:23:59,040 talking about here I've listed the 619 00:24:03,140 --> 00:24:01,320 number of protein subunits associated 620 00:24:03,590 --> 00:24:03,150 with those six six thirteen eight eight 621 00:24:05,150 --> 00:24:03,600 nine 622 00:24:07,160 --> 00:24:05,160 so we're I think that we're talking 623 00:24:09,380 --> 00:24:07,170 about a really quite late an advanced 624 00:24:10,820 --> 00:24:09,390 stage in biological evolution by the 625 00:24:15,770 --> 00:24:10,830 time we're talking about using some of 626 00:24:17,740 --> 00:24:15,780 these protein pumps and so that got me 627 00:24:21,020 --> 00:24:17,750 thinking how could this ever happen and 628 00:24:22,220 --> 00:24:21,030 as I said before there's two ways that 629 00:24:24,050 --> 00:24:22,230 cells can actually generate a 630 00:24:26,510 --> 00:24:24,060 chemiosmotic potential one is to use a 631 00:24:30,250 --> 00:24:26,520 pump and one is to just have an input of 632 00:24:32,930 --> 00:24:30,260 electrical charge inside of it last year 633 00:24:34,940 --> 00:24:32,940 two years ago now two years ago we 634 00:24:37,220 --> 00:24:34,950 discovered a brand of archaea that 635 00:24:39,650 --> 00:24:37,230 covers itself with a conductive protein 636 00:24:41,780 --> 00:24:39,660 blanket and it's able to export 637 00:24:43,670 --> 00:24:41,790 electrons from it itself and so what I 638 00:24:45,290 --> 00:24:43,680 started considering was the reverse of 639 00:24:46,190 --> 00:24:45,300 the process that we discovered two years 640 00:24:48,500 --> 00:24:46,200 ago it 641 00:24:51,530 --> 00:24:48,510 would it be possible to run a managed 642 00:24:54,710 --> 00:24:51,540 and Excel in the way of having direct 643 00:24:56,360 --> 00:24:54,720 electrons enter into the cell and in 644 00:24:59,000 --> 00:24:56,370 that way generate a chemiosmotic 645 00:25:02,030 --> 00:24:59,010 potential by virtue simply of proton 646 00:25:04,970 --> 00:25:02,040 consumption so anytime you reduce co2 it 647 00:25:06,770 --> 00:25:04,980 it requires hydrogen to do that in the 648 00:25:09,260 --> 00:25:06,780 form of protons and that might be a way 649 00:25:10,760 --> 00:25:09,270 of inputting a negative charge into the 650 00:25:12,350 --> 00:25:10,770 cell and generating a cammeo somatic 651 00:25:16,280 --> 00:25:12,360 potential and what I'm trying to get at 652 00:25:17,600 --> 00:25:16,290 here is to imagine a selection pressure 653 00:25:19,040 --> 00:25:17,610 that might have resulted in the 654 00:25:22,100 --> 00:25:19,050 emergence of these pumps at some point 655 00:25:24,800 --> 00:25:22,110 in in biological history you could do 656 00:25:26,330 --> 00:25:24,810 this with any any autotrophic metabolism 657 00:25:28,130 --> 00:25:26,340 you could take the RS CA cycle you could 658 00:25:30,800 --> 00:25:28,140 take in a CD gen anytime you put 659 00:25:32,390 --> 00:25:30,810 electrons on to co2 it requires protons 660 00:25:34,760 --> 00:25:32,400 and so you can consume protons this way 661 00:25:36,200 --> 00:25:34,770 and make a chemiosmotic potential but 662 00:25:38,780 --> 00:25:36,210 where would the electrons come from 663 00:25:40,280 --> 00:25:38,790 where would the organic carbon come from 664 00:25:43,520 --> 00:25:40,290 for this whole process to be happening 665 00:25:44,990 --> 00:25:43,530 and what about the catalysts I blew my 666 00:25:46,340 --> 00:25:45,000 cover earlier and I told you I was going 667 00:25:49,130 --> 00:25:46,350 to talk a little bit about hydrothermal 668 00:25:52,010 --> 00:25:49,140 events today and I started considering 669 00:25:54,830 --> 00:25:52,020 what about this possibility kind of 670 00:25:59,540 --> 00:25:54,840 riffing on Mike Russell's concepts where 671 00:26:01,300 --> 00:25:59,550 if there was a high pH full loaded with 672 00:26:05,540 --> 00:26:01,310 hydrogen hydrogen or Mille event 673 00:26:07,250 --> 00:26:05,550 surrounded by our kind of a slightly 674 00:26:08,690 --> 00:26:07,260 acidic ocean it seems like I got my 675 00:26:11,560 --> 00:26:08,700 number wrong compared to the last talk 676 00:26:14,600 --> 00:26:11,570 should be around 6.5 I think compared to 677 00:26:15,920 --> 00:26:14,610 Vernors calculation but you have a 678 00:26:18,170 --> 00:26:15,930 slightly acidic ocean and what this does 679 00:26:19,850 --> 00:26:18,180 between acid and bases it gives you a 680 00:26:22,730 --> 00:26:19,860 nerd steam potential it makes the 681 00:26:25,220 --> 00:26:22,740 hydrogen more reducing or a more more 682 00:26:27,950 --> 00:26:25,230 electronegative and we could make a 683 00:26:30,560 --> 00:26:27,960 cartoon diagram like this where you 684 00:26:32,390 --> 00:26:30,570 could have hydrogen oxidation coupled to 685 00:26:35,630 --> 00:26:32,400 co2 reduction but that would happen over 686 00:26:37,570 --> 00:26:35,640 a conductive mineral layer here and so 687 00:26:39,410 --> 00:26:37,580 maybe that would be a way of 688 00:26:42,410 --> 00:26:39,420 accumulating organic carbon on the 689 00:26:44,840 --> 00:26:42,420 surface of one of these vents and this 690 00:26:47,660 --> 00:26:44,850 is kind of totally inspired by my 691 00:26:49,460 --> 00:26:47,670 colleagues nakamura-san and yamamoto 692 00:26:51,080 --> 00:26:49,470 saad who actually discovered that a lot 693 00:26:55,010 --> 00:26:51,090 of hydrothermal vents are electronically 694 00:26:57,980 --> 00:26:55,020 conductive and then this is where I'm 695 00:26:59,930 --> 00:26:57,990 really dreaming here but maybe this 696 00:27:01,730 --> 00:26:59,940 would be a way for cells to actually be 697 00:27:06,169 --> 00:27:01,740 there and generating and chemiosmotic 698 00:27:08,840 --> 00:27:06,179 potentials simply by influx of negative 699 00:27:10,850 --> 00:27:08,850 charge and not having any pumps so 700 00:27:13,100 --> 00:27:10,860 possibly before the origination of 701 00:27:14,659 --> 00:27:13,110 chemiosmotic pumping there was the 702 00:27:16,249 --> 00:27:14,669 introduction of negative charge in a way 703 00:27:19,639 --> 00:27:16,259 that led to a selection pressure that 704 00:27:21,080 --> 00:27:19,649 would allow pumps to exist okay this is 705 00:27:23,560 --> 00:27:21,090 all just dreams how are we going to do 706 00:27:26,680 --> 00:27:23,570 it in the lab we're starting to make 707 00:27:29,060 --> 00:27:26,690 Hydra kind of very simple a simple 708 00:27:31,279 --> 00:27:29,070 simulated hydrothermal vents where we 709 00:27:32,749 --> 00:27:31,289 pump a solution of iron and carbonate 710 00:27:34,909 --> 00:27:32,759 and other carbon compounds and on the 711 00:27:36,950 --> 00:27:34,919 Left we put that into a sulphate 712 00:27:38,899 --> 00:27:36,960 solution on the right we can make a iron 713 00:27:41,119 --> 00:27:38,909 sulfur layer and we can ask this 714 00:27:43,220 --> 00:27:41,129 question can you actually oxidize 715 00:27:45,259 --> 00:27:43,230 hydrogen and couple that to co2 reaction 716 00:27:47,690 --> 00:27:45,269 or other carbon molecule reduction in 717 00:27:49,369 --> 00:27:47,700 this flat diagram the thing on the left 718 00:27:50,990 --> 00:27:49,379 would be the ocean that side of the 719 00:27:52,279 --> 00:27:51,000 layer would be the ocean and the and the 720 00:27:56,840 --> 00:27:52,289 solution on the right would be the 721 00:27:59,450 --> 00:27:56,850 actual hydrothermal vent solution so 722 00:28:01,700 --> 00:27:59,460 woojae Chang who's been a visitor 723 00:28:04,190 --> 00:28:01,710 supported by the Eon program twice now 724 00:28:07,639 --> 00:28:04,200 he's he's now working on this and also 725 00:28:10,070 --> 00:28:07,649 Victor Sojo who is with with us today he 726 00:28:13,850 --> 00:28:10,080 came up with the same idea independently 727 00:28:17,629 --> 00:28:13,860 and he's now a visitor at Rican and he's 728 00:28:19,399 --> 00:28:17,639 supported by an MPO fellowship and we're 729 00:28:21,919 --> 00:28:19,409 collaborating together Victor's using a 730 00:28:22,369 --> 00:28:21,929 more organized solution than what we're 731 00:28:24,919 --> 00:28:22,379 using 732 00:28:27,470 --> 00:28:24,929 but they both accomplish the same goal 733 00:28:29,690 --> 00:28:27,480 and the overall experiments that we can 734 00:28:33,680 --> 00:28:29,700 start to do is pump this thing up full 735 00:28:35,990 --> 00:28:33,690 of iron pump it up full of iron and a 736 00:28:37,999 --> 00:28:36,000 carbon solution hydrogen on the other 737 00:28:39,649 --> 00:28:38,009 side and ask this question again I think 738 00:28:41,090 --> 00:28:39,659 we're looking at do you get electron 739 00:28:42,649 --> 00:28:41,100 transfer from one side to the other 740 00:28:45,320 --> 00:28:42,659 hydrogen oxidation couple two co2 741 00:28:47,720 --> 00:28:45,330 reduction that's pretty hard we're not 742 00:28:48,919 --> 00:28:47,730 sure about it Chris butch had the good 743 00:28:51,320 --> 00:28:48,929 idea thanks Chris 744 00:28:52,639 --> 00:28:51,330 to put an already reduced carbon 745 00:28:54,590 --> 00:28:52,649 molecule in there and use that to test 746 00:28:57,409 --> 00:28:54,600 we've got these really weak and sketchy 747 00:29:00,529 --> 00:28:57,419 NMR peaks that seem like oxalic acid was 748 00:29:02,060 --> 00:29:00,539 turned into an alcohol and we're 749 00:29:03,799 --> 00:29:02,070 currently working on developing that 750 00:29:04,789 --> 00:29:03,809 more we've also got even more weak data 751 00:29:06,980 --> 00:29:04,799 that where it looks like we're seeing 752 00:29:08,600 --> 00:29:06,990 acetate but hold on because I don't want 753 00:29:10,999 --> 00:29:08,610 to present that to you until I'm more 754 00:29:12,799 --> 00:29:11,009 sure about it these are just very very 755 00:29:15,470 --> 00:29:12,809 preliminary results that 756 00:29:17,119 --> 00:29:15,480 are aimed at testing the hypothesis that 757 00:29:18,739 --> 00:29:17,129 organic material could accumulate on the 758 00:29:20,239 --> 00:29:18,749 exterior of a hydrothermal vent and that 759 00:29:22,190 --> 00:29:20,249 might have been an area where chemical 760 00:29:23,659 --> 00:29:22,200 evolution might be happening previous 761 00:29:25,039 --> 00:29:23,669 hypotheses in the origin of life have 762 00:29:26,539 --> 00:29:25,049 all said it was happening on the inside 763 00:29:28,610 --> 00:29:26,549 all I want to suggest to you that 764 00:29:32,330 --> 00:29:28,620 outside is a more positive it's a more 765 00:29:36,019 --> 00:29:32,340 reasonable location and I'm so far out 766 00:29:38,690 --> 00:29:36,029 of time this is I want us to remember 767 00:29:40,399 --> 00:29:38,700 that when people talk about hydrothermal 768 00:29:41,869 --> 00:29:40,409 vents in the origin of life everybody's 769 00:29:43,369 --> 00:29:41,879 talking about a different thing and they 770 00:29:45,440 --> 00:29:43,379 don't often it acknowledged that and 771 00:29:46,460 --> 00:29:45,450 this is just a slide ask me for it later 772 00:29:47,779 --> 00:29:46,470 and I'll discuss for it later I don't 773 00:29:49,580 --> 00:29:47,789 have time to talk about it but ever 774 00:29:50,930 --> 00:29:49,590 since 1993 when Mike Russell and 775 00:29:52,249 --> 00:29:50,940 colleagues started talking about 776 00:29:54,019 --> 00:29:52,259 hydrothermal vents in the original life 777 00:29:55,129 --> 00:29:54,029 these concepts have been presented in 778 00:29:56,989 --> 00:29:55,139 slightly different ways and I think 779 00:29:58,850 --> 00:29:56,999 that's a little bit confusing it's okay 780 00:29:59,899 --> 00:29:58,860 it's a complicated world but be careful 781 00:30:02,239 --> 00:29:59,909 when you hear somebody talking about the 782 00:30:04,340 --> 00:30:02,249 origin of life finally I have wonderful 783 00:30:06,320 --> 00:30:04,350 colleagues Reva Nakamura widget hang and 784 00:30:07,639 --> 00:30:06,330 I'm really happy that Victor Soto has 785 00:30:09,470 --> 00:30:07,649 come to Japan and is working and 786 00:30:11,090 --> 00:30:09,480 collaboration now and these are my 787 00:30:21,379 --> 00:30:11,100 summary or marks thank you very much for 788 00:30:24,590 --> 00:30:21,389 your time do we have questions on the 789 00:30:27,139 --> 00:30:24,600 far side there first right here uh I 790 00:30:28,789 --> 00:30:27,149 think that what you said about the 791 00:30:30,799 --> 00:30:28,799 Martin paper I don't I think he should 792 00:30:32,659 --> 00:30:30,809 write that up and that's kind of 793 00:30:34,759 --> 00:30:32,669 important that that be understood by 794 00:30:37,009 --> 00:30:34,769 everybody so I would like to encourage 795 00:30:37,369 --> 00:30:37,019 you to do that but that's not my 796 00:30:45,739 --> 00:30:37,379 question 797 00:30:47,149 --> 00:30:45,749 about gradients and chemiosmosis and you 798 00:30:48,799 --> 00:30:47,159 know you said that that's universal to 799 00:30:50,119 --> 00:30:48,809 all cells but you know that you could 800 00:30:52,820 --> 00:30:50,129 say that there's a huge list of things 801 00:30:55,039 --> 00:30:52,830 right phosphorylation condensation 802 00:30:58,009 --> 00:30:55,049 dehydration and so I don't quite 803 00:31:00,379 --> 00:30:58,019 understand why you have chosen that as I 804 00:31:02,090 --> 00:31:00,389 mean you can store energy all kinds of 805 00:31:04,340 --> 00:31:02,100 different ways chemically and some of 806 00:31:06,470 --> 00:31:04,350 them are very easy and it seems like you 807 00:31:08,889 --> 00:31:06,480 like like you said if you look at these 808 00:31:12,440 --> 00:31:08,899 synthetases they're so complicated so 809 00:31:15,680 --> 00:31:12,450 I'm just not understanding why you're 810 00:31:20,570 --> 00:31:15,690 focused on the chemiosmosis as something 811 00:31:21,769 --> 00:31:20,580 early in the origin of life thanks for 812 00:31:23,650 --> 00:31:21,779 that question and thanks very encouraged 813 00:31:26,050 --> 00:31:23,660 me too 814 00:31:27,430 --> 00:31:26,060 I would like to be more focused on 815 00:31:30,280 --> 00:31:27,440 something like substrate level 816 00:31:32,080 --> 00:31:30,290 phosphorylation the trouble with 817 00:31:33,640 --> 00:31:32,090 substrate level phosphorylation it just 818 00:31:37,540 --> 00:31:33,650 takes more chemical potential to drive 819 00:31:39,640 --> 00:31:37,550 it if you use ATP and ATP as cells use 820 00:31:42,210 --> 00:31:39,650 it today however this is all just a 821 00:31:44,890 --> 00:31:42,220 function of concentrations right and so 822 00:31:48,670 --> 00:31:44,900 what I would like to learn more about 823 00:31:50,740 --> 00:31:48,680 and consider together is what how far 824 00:31:52,210 --> 00:31:50,750 from equilibrium were the first cells 825 00:31:54,250 --> 00:31:52,220 that's what this is going to come down 826 00:31:56,350 --> 00:31:54,260 to in many ways it seems like these 827 00:31:58,360 --> 00:31:56,360 chemiosmotic cells these methanogens and 828 00:32:00,580 --> 00:31:58,370 asita jhin's they've just become super 829 00:32:02,770 --> 00:32:00,590 super adept at living with really really 830 00:32:04,870 --> 00:32:02,780 low chemical potentials they both 831 00:32:06,910 --> 00:32:04,880 stopped at my minus 30 kilojoules per 832 00:32:09,700 --> 00:32:06,920 mole because they both pump one to two 833 00:32:11,470 --> 00:32:09,710 ions at one chemiosmotic step that's 834 00:32:13,630 --> 00:32:11,480 about as low as we know anything can go 835 00:32:15,100 --> 00:32:13,640 and so in one way it seems like they're 836 00:32:19,480 --> 00:32:15,110 super super adapted to low chemical 837 00:32:22,210 --> 00:32:19,490 potentials yeah so I'm not necessarily 838 00:32:23,980 --> 00:32:22,220 tied to it yeah and I think it would be 839 00:32:26,470 --> 00:32:23,990 better if we could it would be very 840 00:32:28,300 --> 00:32:26,480 helpful if we could consider other sets 841 00:32:31,000 --> 00:32:28,310 of molecules that chemical energy could 842 00:32:33,070 --> 00:32:31,010 be channeled into and then used broadly 843 00:32:34,570 --> 00:32:33,080 distributed in a metabolic Network I'm 844 00:32:38,110 --> 00:32:34,580 not sure exactly what that is but let's 845 00:32:39,640 --> 00:32:38,120 talk more later yeah comment did a 846 00:32:41,260 --> 00:32:39,650 question you notice that in his question 847 00:32:43,960 --> 00:32:41,270 he used energy storage rather than 848 00:32:45,550 --> 00:32:43,970 energy conservation I can I can support 849 00:32:47,200 --> 00:32:45,560 that wholeheartedly as a physicist cuz 850 00:32:49,360 --> 00:32:47,210 energy conservation is the first law of 851 00:32:51,400 --> 00:32:49,370 thermodynamics and everything does it 852 00:32:53,770 --> 00:32:51,410 not just life-forms that are trying to 853 00:32:55,810 --> 00:32:53,780 say I would say storage of free energy 854 00:32:59,260 --> 00:32:55,820 might be even more appropriate comment 855 00:33:00,700 --> 00:32:59,270 question in these nine unit things and 856 00:33:02,310 --> 00:33:00,710 the six unit things I think you called 857 00:33:05,560 --> 00:33:02,320 them R and F these are transmembrane 858 00:33:08,470 --> 00:33:05,570 proteins or in any case have you looked 859 00:33:10,120 --> 00:33:08,480 at the phylogenetic trees of the various 860 00:33:12,730 --> 00:33:10,130 versions of them to see if they have a 861 00:33:14,740 --> 00:33:12,740 common ancestor in which you might say 862 00:33:16,870 --> 00:33:14,750 oh there were three subunits and they 863 00:33:18,280 --> 00:33:16,880 were that they overlap between them are 864 00:33:21,340 --> 00:33:18,290 you saying when you were they nine 865 00:33:22,900 --> 00:33:21,350 separate sub units that did not overlap 866 00:33:26,860 --> 00:33:22,910 with the six or and there's no 867 00:33:29,410 --> 00:33:26,870 connection identifiable between them I 868 00:33:30,880 --> 00:33:29,420 haven't I haven't done that and maybe 869 00:33:32,920 --> 00:33:30,890 other people have and if anybody else 870 00:33:34,780 --> 00:33:32,930 and there has already done that please 871 00:33:36,760 --> 00:33:34,790 pipe up I know there's ATP synthase 872 00:33:37,570 --> 00:33:36,770 trees but I didn't anyone try to connect 873 00:33:40,690 --> 00:33:37,580 that to what you call 874 00:33:44,979 --> 00:33:40,700 or an F tree yeah yeah you can yeah and 875 00:33:46,899 --> 00:33:44,989 you can make the rnf tree it comes down 876 00:33:48,639 --> 00:33:46,909 to there's going to be subunits that 877 00:33:51,940 --> 00:33:48,649 look like it and are similar to it but 878 00:33:53,320 --> 00:33:51,950 don't bind to it and so he Ben it's you 879 00:33:54,729 --> 00:33:53,330 have to only consider that ones that are 880 00:33:56,320 --> 00:33:54,739 the full package it's kind of like 881 00:33:57,940 --> 00:33:56,330 looking at the evolution of the eye you 882 00:34:00,039 --> 00:33:57,950 know like it happened with all these 883 00:34:01,299 --> 00:34:00,049 different things happening unrelated and 884 00:34:05,049 --> 00:34:01,309 then eventually it was started forming 885 00:34:06,580 --> 00:34:05,059 this complex so there's still proteins 886 00:34:07,989 --> 00:34:06,590 that are out there that look like these 887 00:34:10,960 --> 00:34:07,999 different subunits but they're different 888 00:34:12,849 --> 00:34:10,970 doing different jobs so I think it makes 889 00:34:14,169 --> 00:34:12,859 that analysis a little bit hard but 890 00:34:16,329 --> 00:34:14,179 again I haven't actually done that 891 00:34:19,409 --> 00:34:16,339 analysis if anybody has would be cool to 892 00:34:22,059 --> 00:34:19,419 talk about that's a good question Eric 893 00:34:24,789 --> 00:34:22,069 Sean hi there were two points in your 894 00:34:26,500 --> 00:34:24,799 talk where there were sort of equally 895 00:34:28,030 --> 00:34:26,510 urgent things where I wanted to hear 896 00:34:30,280 --> 00:34:28,040 your opinion because you've thought well 897 00:34:32,680 --> 00:34:30,290 about some of this I agree with your 898 00:34:35,530 --> 00:34:32,690 point about not wanting to trash 899 00:34:38,859 --> 00:34:35,540 articles there's no use in that but at 900 00:34:40,960 --> 00:34:38,869 the same time within proper 901 00:34:43,389 --> 00:34:40,970 phylogenetics people have put a lot of 902 00:34:45,280 --> 00:34:43,399 effort into defining things like maximum 903 00:34:47,740 --> 00:34:45,290 likelihood methods and Bayesian methods 904 00:34:50,889 --> 00:34:47,750 for which they understand the properties 905 00:34:53,500 --> 00:34:50,899 of these statistical approaches as 906 00:34:55,510 --> 00:34:53,510 probability models now they're often 907 00:34:57,129 --> 00:34:55,520 under specified and so they leave out a 908 00:34:59,740 --> 00:34:57,139 lot of what we would like to consider in 909 00:35:02,589 --> 00:34:59,750 data but one of the reasons people don't 910 00:35:05,109 --> 00:35:02,599 just dream up criteria and then write 911 00:35:07,030 --> 00:35:05,119 papers about them is that criteria with 912 00:35:08,710 --> 00:35:07,040 no known properties give you answers 913 00:35:10,900 --> 00:35:08,720 that you don't know how to interpret and 914 00:35:12,789 --> 00:35:10,910 so for a lot of these deep protein 915 00:35:17,410 --> 00:35:12,799 phylogeny Xand questions about what is 916 00:35:19,870 --> 00:35:17,420 in old organisms I have wondered how 917 00:35:22,539 --> 00:35:19,880 much of this can we referee by putting 918 00:35:24,190 --> 00:35:22,549 it against models with known properties 919 00:35:26,319 --> 00:35:24,200 and figuring out whether we believe it 920 00:35:28,480 --> 00:35:26,329 at all but before I ask you to answer 921 00:35:31,809 --> 00:35:28,490 that there's a question barely related 922 00:35:34,329 --> 00:35:31,819 to it because this is in the domain of 923 00:35:35,829 --> 00:35:34,339 semantics material semantics information 924 00:35:37,930 --> 00:35:35,839 that's hard to put into maximum 925 00:35:40,660 --> 00:35:37,940 likelihood models but seems relevant 926 00:35:44,109 --> 00:35:40,670 it's the next point about where we place 927 00:35:46,660 --> 00:35:44,119 old ATP synthesis and the complexity of 928 00:35:50,109 --> 00:35:46,670 them in addition to the protein itself 929 00:35:51,370 --> 00:35:50,119 if I look at methanogens the role of the 930 00:35:53,890 --> 00:35:51,380 ATP synthase is 931 00:35:55,930 --> 00:35:53,900 outside both the energy branch on the 932 00:35:58,569 --> 00:35:55,940 carbon fixation branch of the one-carbon 933 00:36:00,460 --> 00:35:58,579 system you use it to capture energy to 934 00:36:03,880 --> 00:36:00,470 do the rest of what the cell needs to do 935 00:36:06,849 --> 00:36:03,890 if I look at a cedar jens the ATP 936 00:36:08,349 --> 00:36:06,859 synthase stands actually between the 937 00:36:11,079 --> 00:36:08,359 energy branch and the carbon fixation 938 00:36:13,089 --> 00:36:11,089 branch so if it were not there the 939 00:36:14,799 --> 00:36:13,099 fundamental function of using the c1 940 00:36:17,410 --> 00:36:14,809 metabolism to couple and exergonic 941 00:36:18,130 --> 00:36:17,420 process to a carbon fixation would be 942 00:36:20,380 --> 00:36:18,140 impaired 943 00:36:22,839 --> 00:36:20,390 so architectural II they have extremely 944 00:36:24,579 --> 00:36:22,849 different roles so when we look at that 945 00:36:27,900 --> 00:36:24,589 and we try to figure out even if they 946 00:36:31,450 --> 00:36:27,910 are deep or basal claves respectively in 947 00:36:33,640 --> 00:36:31,460 archaea and bacteria we look at the very 948 00:36:35,589 --> 00:36:33,650 different roles of the ATP synthase 949 00:36:37,390 --> 00:36:35,599 architectural e in the two systems and 950 00:36:38,920 --> 00:36:37,400 then we know that phylogenetic 951 00:36:41,499 --> 00:36:38,930 reconstruction for these things that 952 00:36:43,930 --> 00:36:41,509 have more than one homologous group are 953 00:36:45,670 --> 00:36:43,940 difficult what is the right way to think 954 00:36:50,160 --> 00:36:45,680 in a disciplined way about what ancient 955 00:36:59,319 --> 00:36:54,400 thank you that's yeah I have a lot to 956 00:37:00,579 --> 00:36:59,329 think about now for the for the first 957 00:37:06,069 --> 00:37:00,589 question 958 00:37:10,299 --> 00:37:06,079 I don't yeah I don't know of the 959 00:37:13,779 --> 00:37:10,309 literature where people have taken 960 00:37:15,700 --> 00:37:13,789 sequences if this isn't done let's do it 961 00:37:17,470 --> 00:37:15,710 let's take sequences and put them in 962 00:37:21,579 --> 00:37:17,480 little artificial cells and then have 963 00:37:23,890 --> 00:37:21,589 them evolve with a certain evolutionary 964 00:37:26,499 --> 00:37:23,900 model and then build trees and then 965 00:37:28,749 --> 00:37:26,509 build trees and then let it go and keep 966 00:37:30,910 --> 00:37:28,759 building trees I do know of examples 967 00:37:34,269 --> 00:37:30,920 where it seems pretty obvious just based 968 00:37:36,430 --> 00:37:34,279 on actual domains and so when we when we 969 00:37:39,160 --> 00:37:36,440 have sequence information and we and we 970 00:37:41,380 --> 00:37:39,170 also have domain information sometimes 971 00:37:43,269 --> 00:37:41,390 these domains can swap around and you 972 00:37:45,160 --> 00:37:43,279 and you and this is a glaring example 973 00:37:47,710 --> 00:37:45,170 where you know your secret your sequence 974 00:37:51,789 --> 00:37:47,720 alignment is wrong but it works you can 975 00:37:54,339 --> 00:37:51,799 align anything and in these in in these 976 00:37:56,230 --> 00:37:54,349 cases I do know of cases where the 977 00:37:57,970 --> 00:37:56,240 branching order does swap around and so 978 00:38:00,700 --> 00:37:57,980 something that should be very very far 979 00:38:02,470 --> 00:38:00,710 out and ends up being basal because 980 00:38:03,630 --> 00:38:02,480 based on the model that becomes the most 981 00:38:08,310 --> 00:38:03,640 probable thing 982 00:38:11,880 --> 00:38:08,320 but it you you have to supervise the 983 00:38:13,500 --> 00:38:11,890 computer when you do this it might be 984 00:38:15,840 --> 00:38:13,510 worthwhile considering some simulations 985 00:38:16,980 --> 00:38:15,850 if people haven't done to do that the 986 00:38:19,080 --> 00:38:16,990 other way to do that is to go to the 987 00:38:20,880 --> 00:38:19,090 Levin and let the let the microbes crank 988 00:38:27,420 --> 00:38:20,890 but that takes more time than the 989 00:38:31,230 --> 00:38:27,430 simulation the second question about met 990 00:38:32,790 --> 00:38:31,240 antigens and heceta genes and this 991 00:38:38,190 --> 00:38:32,800 different structure that accomplishes 992 00:38:40,530 --> 00:38:38,200 roughly the same thing I don't they 993 00:38:44,880 --> 00:38:40,540 would I don't know why there's not a 994 00:38:46,620 --> 00:38:44,890 third way this is a way to back out of 995 00:38:47,760 --> 00:38:46,630 answering that complicated question but 996 00:38:49,200 --> 00:38:47,770 there is kind of a third way the 997 00:38:52,380 --> 00:38:49,210 methanogens and the exceeded ends both 998 00:38:55,140 --> 00:38:52,390 come in at in at least you know three 999 00:38:56,910 --> 00:38:55,150 different flavors apiece and they all 1000 00:38:57,900 --> 00:38:56,920 have different protein subunits and 1001 00:38:59,220 --> 00:38:57,910 they're all accomplishing the same 1002 00:39:02,040 --> 00:38:59,230 reaction but they do it with different 1003 00:39:04,710 --> 00:39:02,050 enzyme arrangements or architectures 1004 00:39:07,080 --> 00:39:04,720 inside of the cell and so in my head I 1005 00:39:10,140 --> 00:39:07,090 think oh this is part of the this is 1006 00:39:12,150 --> 00:39:10,150 part of how material responds to an 1007 00:39:14,070 --> 00:39:12,160 energy flow this is how it can get 1008 00:39:16,620 --> 00:39:14,080 organized and in methanogens and the 1009 00:39:18,150 --> 00:39:16,630 citizens it's somewhat degenerate in the 1010 00:39:19,650 --> 00:39:18,160 sense that they both pull the hydrogen 1011 00:39:21,660 --> 00:39:19,660 concentration to the pretty much the 1012 00:39:24,930 --> 00:39:21,670 exact same chemical potential but 1013 00:39:27,060 --> 00:39:24,940 they're doing it in different ways yeah 1014 00:39:30,420 --> 00:39:27,070 I think the only way for me to safely 1015 00:39:32,360 --> 00:39:30,430 back out is to say like what would be 1016 00:39:35,940 --> 00:39:32,370 the other ways that that could work and 1017 00:39:37,170 --> 00:39:35,950 that might be good to look for there 1018 00:39:39,990 --> 00:39:37,180 should be different I see de gens out 1019 00:39:42,510 --> 00:39:40,000 there too that don't link the processes 1020 00:39:44,160 --> 00:39:42,520 in the same way maybe or if there's not 1021 00:39:46,620 --> 00:39:44,170 maybe it's something really special I'm 1022 00:39:51,240 --> 00:39:46,630 not quite sure about that very cool 1023 00:39:52,560 --> 00:39:51,250 thank you next question here I just to 1024 00:39:54,240 --> 00:39:52,570 follow up on that a little bit I think 1025 00:39:56,400 --> 00:39:54,250 it is interesting that you focus on 1026 00:40:00,600 --> 00:39:56,410 heceta genesis methanogenesis because 1027 00:40:02,790 --> 00:40:00,610 there are arguments against looking at 1028 00:40:05,250 --> 00:40:02,800 those as ancient forms of metabolism 1029 00:40:08,430 --> 00:40:05,260 well they may be more derived Nitschke 1030 00:40:10,470 --> 00:40:08,440 and Russell's work where they're looking 1031 00:40:11,880 --> 00:40:10,480 at those processes and saying that they 1032 00:40:14,190 --> 00:40:11,890 must be more derived because you only 1033 00:40:16,590 --> 00:40:14,200 see a Seeta Genesis in bacteria you only 1034 00:40:17,520 --> 00:40:16,600 see methane in Genesis in archaea and so 1035 00:40:20,760 --> 00:40:17,530 they may have been derived 1036 00:40:23,070 --> 00:40:20,770 later on far after the leuco that's more 1037 00:40:24,270 --> 00:40:23,080 of a comment than a question though but 1038 00:40:26,280 --> 00:40:24,280 I was wondering if you could touch a 1039 00:40:28,200 --> 00:40:26,290 little bit on a statement you made 1040 00:40:30,270 --> 00:40:28,210 earlier about how it's more likely that 1041 00:40:31,680 --> 00:40:30,280 you would find this early metabolism on 1042 00:40:33,210 --> 00:40:31,690 the outside of the vents then on the 1043 00:40:39,060 --> 00:40:33,220 inside of the vents can you explain why 1044 00:40:40,410 --> 00:40:39,070 you feel that way so the for the for the 1045 00:40:42,690 --> 00:40:40,420 first concept I think you're completely 1046 00:40:44,610 --> 00:40:42,700 right and I think that all the stuff 1047 00:40:46,230 --> 00:40:44,620 that I've talked about here today which 1048 00:40:47,790 --> 00:40:46,240 references modern biology might be 1049 00:40:50,610 --> 00:40:47,800 totally misguided to talk about biology 1050 00:40:53,160 --> 00:40:50,620 in any way four billion years ago I'm so 1051 00:40:54,720 --> 00:40:53,170 comfortable with saying that I'm a 1052 00:40:56,250 --> 00:40:54,730 little bit radical that I would be 1053 00:40:58,590 --> 00:40:56,260 totally fine if there's a completely 1054 00:41:00,630 --> 00:40:58,600 alternative genetic code or no genetic 1055 00:41:01,560 --> 00:41:00,640 code or something four billion years ago 1056 00:41:04,500 --> 00:41:01,570 and a totally different type of 1057 00:41:06,000 --> 00:41:04,510 metabolism so this is part of what I 1058 00:41:09,260 --> 00:41:06,010 also want to talk about at our after 1059 00:41:12,210 --> 00:41:09,270 shop is how far can we go we've got 1060 00:41:14,070 --> 00:41:12,220 we've got some decent rock data that 1061 00:41:16,620 --> 00:41:14,080 there was life based on light isotopes 1062 00:41:17,760 --> 00:41:16,630 so like 3.8 billion years ago but so 1063 00:41:19,200 --> 00:41:17,770 what maybe it was a different form of 1064 00:41:21,360 --> 00:41:19,210 life that didn't didn't do anything like 1065 00:41:22,830 --> 00:41:21,370 that and what are our safeguards so I 1066 00:41:24,330 --> 00:41:22,840 think this is a totally valid concern 1067 00:41:26,550 --> 00:41:24,340 and it would be awesome to figure out 1068 00:41:30,780 --> 00:41:26,560 ways to guard ourselves against that the 1069 00:41:32,340 --> 00:41:30,790 second question is only because of this 1070 00:41:35,670 --> 00:41:32,350 concept of the nernst and potential 1071 00:41:37,380 --> 00:41:35,680 difference so if you take hydrogen at pH 1072 00:41:39,330 --> 00:41:37,390 0 the way we define it is that the redox 1073 00:41:40,860 --> 00:41:39,340 potential is zero that is it's not it 1074 00:41:42,810 --> 00:41:40,870 doesn't want to give electrons out it's 1075 00:41:44,540 --> 00:41:42,820 at equilibrium with taking them and as 1076 00:41:48,240 --> 00:41:44,550 you crank the pH up higher and higher 1077 00:41:50,490 --> 00:41:48,250 hydrogen h2 becomes more less and less 1078 00:41:52,140 --> 00:41:50,500 stable and it wants to shoot out its 1079 00:41:54,600 --> 00:41:52,150 electrons more and more or when the 1080 00:41:56,460 --> 00:41:54,610 electrons get shot out is that a more 1081 00:41:58,740 --> 00:41:56,470 reducing potential so if you can do that 1082 00:42:00,990 --> 00:41:58,750 at pH 10 the electrons really come 1083 00:42:02,760 --> 00:42:01,000 screaming out of the hydrogen and if 1084 00:42:06,090 --> 00:42:02,770 those if those electrons go over a 1085 00:42:08,210 --> 00:42:06,100 conductive mineral wall they can hit the 1086 00:42:11,070 --> 00:42:08,220 carbon and reduce it so 1087 00:42:13,200 --> 00:42:11,080 thermodynamically you can't it's really 1088 00:42:14,880 --> 00:42:13,210 hard to have carbon reduction in the 1089 00:42:16,200 --> 00:42:14,890 inside because the redox potential if 1090 00:42:19,260 --> 00:42:16,210 the carbon also gets more and more 1091 00:42:21,930 --> 00:42:19,270 negative so the two things shift but if 1092 00:42:24,780 --> 00:42:21,940 you can separate the protons from the 1093 00:42:26,220 --> 00:42:24,790 carbon but not the electrons that's when 1094 00:42:30,210 --> 00:42:26,230 you can have the energy flow happen 1095 00:42:31,330 --> 00:42:30,220 really thermodynamically favorable thank 1096 00:42:33,270 --> 00:42:31,340 you very great talk 1097 00:42:39,580 --> 00:42:33,280 oh thank you hey last question over here 1098 00:42:42,340 --> 00:42:39,590 okay exciting now quickly so this means 1099 00:42:44,830 --> 00:42:42,350 they appear is a gradient in pH is a 1100 00:42:49,240 --> 00:42:44,840 reason why I think this is a good 1101 00:42:53,170 --> 00:42:49,250 location and there are any other 1102 00:42:55,570 --> 00:42:53,180 locations earlier cited these kind of pH 1103 00:43:01,780 --> 00:42:55,580 gradient might have existed 1104 00:43:03,160 --> 00:43:01,790 other than hydrothermal systems yes 1105 00:43:04,210 --> 00:43:03,170 although had like other people that 1106 00:43:08,950 --> 00:43:04,220 helped me out because I think they know 1107 00:43:12,010 --> 00:43:08,960 more about the earth with that so but to 1108 00:43:14,620 --> 00:43:12,020 step back as a kind of physiologist and 1109 00:43:16,120 --> 00:43:14,630 and go back to this hydrogen thing when 1110 00:43:17,530 --> 00:43:16,130 we look at methanogens aniseed engines 1111 00:43:20,020 --> 00:43:17,540 today whether or not that's a good guide 1112 00:43:21,700 --> 00:43:20,030 for us is another question they're able 1113 00:43:24,070 --> 00:43:21,710 to live on these low hydrogen partial 1114 00:43:26,710 --> 00:43:24,080 pressures because they can take that 1115 00:43:28,810 --> 00:43:26,720 energy that's happening later on in in 1116 00:43:31,300 --> 00:43:28,820 the formation of methane and kind of 1117 00:43:34,350 --> 00:43:31,310 pipe that energy back up to the initial 1118 00:43:37,690 --> 00:43:34,360 step and so and they have to do that 1119 00:43:38,710 --> 00:43:37,700 they have to pipe the energy up because 1120 00:43:40,120 --> 00:43:38,720 there's not enough hydrogen 1121 00:43:41,890 --> 00:43:40,130 concentration which means that the redox 1122 00:43:43,840 --> 00:43:41,900 potential is not negative enough to 1123 00:43:45,580 --> 00:43:43,850 drive Carbon Reduction in this case it 1124 00:43:47,680 --> 00:43:45,590 should just be spontaneous and the whole 1125 00:43:48,610 --> 00:43:47,690 thing like if if there's catalysts you 1126 00:43:49,870 --> 00:43:48,620 know this is the thing the 1127 00:43:51,730 --> 00:43:49,880 thermodynamics are there but who knows 1128 00:43:53,290 --> 00:43:51,740 if the catalysts are there but it 1129 00:43:55,660 --> 00:43:53,300 becomes a kinetic problem and not a I'm 1130 00:43:57,130 --> 00:43:55,670 not a thermodynamic with the ambient 1131 00:43:58,840 --> 00:43:57,140 concentrations that you might be able to 1132 00:44:02,350 --> 00:43:58,850 get out of one of these vents your 1133 00:44:05,110 --> 00:44:02,360 question is where else would this have 1134 00:44:08,110 --> 00:44:05,120 to be it depends on what we think the 1135 00:44:11,170 --> 00:44:08,120 original electron donor for life was and 1136 00:44:12,340 --> 00:44:11,180 so before the oxygenation of the planet 1137 00:44:14,320 --> 00:44:12,350 there probably wasn't a lot of high 1138 00:44:15,850 --> 00:44:14,330 potential acceptors around so this gets 1139 00:44:18,580 --> 00:44:15,860 us back to our morning talk with Eric 1140 00:44:20,620 --> 00:44:18,590 when you have high electron high 1141 00:44:22,150 --> 00:44:20,630 potential very positive electron 1142 00:44:24,400 --> 00:44:22,160 acceptors around it's kind of a whole 1143 00:44:26,680 --> 00:44:24,410 different metabolic world then when you 1144 00:44:29,650 --> 00:44:26,690 only have low potential electron donors 1145 00:44:31,510 --> 00:44:29,660 around these cells are using co2 as an 1146 00:44:34,180 --> 00:44:31,520 electron acceptor which kind of sucks 1147 00:44:35,740 --> 00:44:34,190 but they're able to do that and they can 1148 00:44:38,530 --> 00:44:35,750 only do that because they can pipe the 1149 00:44:40,810 --> 00:44:38,540 energy back up us we can go eat our 1150 00:44:42,670 --> 00:44:40,820 onigiri and we burn it with oxygen and 1151 00:44:44,110 --> 00:44:42,680 we can we can you know we can do all 1152 00:44:44,650 --> 00:44:44,120 sorts of stuff because there's so much 1153 00:44:49,359 --> 00:44:44,660 energy 1154 00:44:51,400 --> 00:44:49,369 couple so we do need to consider very 1155 00:44:53,650 --> 00:44:51,410 very seriously if hydrogen is the only 1156 00:44:55,900 --> 00:44:53,660 real at electron acceptor for the origin 1157 00:44:57,370 --> 00:44:55,910 of of cells or for powering them there 1158 00:44:59,079 --> 00:44:57,380 might be other ones what else we have 1159 00:45:03,309 --> 00:44:59,089 we've got ferrous iron midpoint 1160 00:45:04,960 --> 00:45:03,319 potentials not good so if if we're 1161 00:45:06,819 --> 00:45:04,970 limited to hydrogen we do have to think 1162 00:45:10,120 --> 00:45:06,829 about how we can charge those electrons 1163 00:45:12,370 --> 00:45:10,130 up biology does it today by rerouting 1164 00:45:15,789 --> 00:45:12,380 the electrons back up this is a way that 1165 00:45:21,099 --> 00:45:15,799 would circumvent that but it yeah I'll 1166 00:45:25,680 --> 00:45:21,109 try to think okay let's thank the