Comparative genomics

From Wikipedia, the free encyclopedia

 

Whole genome alignment is a typical method in comparative genomics. This alignment of eight Yersinia bacteria genomes reveals 78 locally collinear blocks conserved among all eight taxa. Each chromosome has been laid out horizontally and homologous blocks in each genome are shown as identically colored regions linked across genomes. Regions that are inverted relative to Y. pestis KIM are shifted below a genome's center axis.

 

Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks. In this branch of genomics, whole or large parts of genomes resulting from genome projects are compared to study basic biological similarities and differences as well as evolutionary relationships between organisms. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. Therefore, comparative genomic approaches start with making some form of alignment of genome sequences and looking for orthologous sequences (sequences that share a common ancestry) in the aligned genomes and checking to what extent those sequences are conserved. Based on these, genome and molecular evolution are inferred and this may in turn be put in the context of, for example, phenotypic evolution or population genetics.

Virtually started as soon as the whole genomes of two organisms became available (that is, the genomes of the bacteria Haemophilus influenzae and Mycoplasma genitalium) in 1995, comparative genomics is now a standard component of the analysis of every new genome sequence. With the explosion in the number of genome projects due to the advancements in DNA sequencing technologies, particularly the next-generation sequencing methods in late 2000s, this field has become more sophisticated, making it possible to deal with many genomes in a single study. Comparative genomics has revealed high levels of similarity between closely related organisms, such as humans and chimpanzees, and, more surprisingly, similarity between seemingly distantly related organisms, such as humans and the yeast Saccharomyces cerevisiae. It has also showed the extreme diversity of the gene composition in different evolutionary lineages.

History

Comparative genomics has a root in the comparison of virus genomes in the early 1980s. For example, small RNA viruses infecting animals (picornaviruses) and those infecting plants (cowpea mosaic virus) were compared and turned out to share significant sequence similarity and, in part, the order of their genes. In 1986, the first comparative genomic study at a larger scale was published, comparing the genomes of varicella-zoster virus and Epstein-Barr virus that contained more than 100 genes each.

The first complete genome sequence of a cellular organism, that of Haemophilus influenzae Rd, was published in 1995. The second genome sequencing paper was of the small parasitic bacterium Mycoplasma genitalium published in the same year. Starting from this paper, reports on new genomes inevitably became comparative-genomic studies.

The first high-resolution whole genome comparison system was developed in 1998 by Art Delcher, Simon Kasif and Steven Salzberg and applied to the comparison of entire highly related microbial organisms with their collaborators at the Institute for Genomic Research (TIGR). The system is called MUMMER and was described in a publication in Nucleic Acids Research in 1999. The system helps researchers to identify large rearrangements, single base mutations, reversals, tandem repeat expansions and other polymorphisms. In bacteria, MUMMER enables the identification of polymorphisms that are responsible for virulence, pathogenicity, and anti-biotic resistance. The system was also applied to the Minimal Organism Project at TIGR and subsequently to many other comparative genomics projects.

Saccharomyces cerevisiae, the baker's yeast, was the first eukaryote to have its complete genome sequence published in 1996. After the publication of the roundworm Caenorhabditis elegans genome in 1998 and together with the fruit fly Drosophila melanogaster genome in 2000, Gerald M. Rubin and his team published a paper titled "Comparative Genomics of the Eukaryotes", in which they compared the genomes of the eukaryotes D. melanogaster, C. elegans, and S. cerevisiae, as well as the prokaryote H. influenzae. At the same time, Bonnie Berger, Eric Lander, and their team published a paper on whole-genome comparison of human and mouse.

With the publication of the large genomes of vertebrates in the 2000s, including human, the Japanese pufferfish Takifugu rubripes, and mouse, precomputed results of large genome comparisons have been released for downloading or for visualization in a genome browser. Instead of undertaking their own analyses, most biologists can access these large cross-species comparisons and avoid the impracticality caused by the size of the genomes.

Next-generation sequencing methods, which were first introduced in 2007, have produced an enormous amount of genomic data and have allowed researchers to generate multiple (prokaryotic) draft genome sequences at once. These methods can also quickly uncover single-nucleotide polymorphisms, insertions and deletions by mapping unassembled reads against a well annotated reference genome, and thus provide a list of possible gene differences that may be the basis for any functional variation among strains.

Evolutionary principles

One character of biology is evolution, evolutionary theory is also the theoretical foundation of comparative genomics, and at the same time the results of comparative genomics unprecedentedly enriched and developed the theory of evolution. When two or more of the genome sequence are compared, one can deduce the evolutionary relationships of the sequences in a phylogenetic tree. Based on a variety of biological genome data and the study of vertical and horizontal evolution processes, one can understand vital parts of the gene structure and its regulatory function.

Similarity of related genomes is the basis of comparative genomics. If two creatures have a recent common ancestor, the differences between the two species genomes are evolved from the ancestors’ genome. The closer the relationship between two organisms, the higher the similarities between their genomes. If there is close relationship between them, then their genome will display a linear behaviour (synteny), namely some or all of the genetic sequences are conserved. Thus, the genome sequences can be used to identify gene function, by analyzing their homology (sequence similarity) to genes of known function.

Orthologous sequences are related sequences in different species: a gene exists in the original species, the species divided into two species, so genes in new species are orthologous to the sequence in the original species. Paralogous sequences are separated by gene cloning (gene duplication): if a particular gene in the genome is copied, then the copy of the two sequences is paralogous to the original gene. A pair of orthologous sequences is called orthologous pairs (orthologs), a pair of paralogous sequence is called collateral pairs (paralogs). Orthologous pairs usually have the same or similar function, which is not necessarily the case for collateral pairs. In collateral pairs, the sequences tend to evolve into having different functions.

Human FOXP2 gene and evolutionary conservation is shown in and multiple alignment (at bottom of figure) in this image from the UCSC Genome Browser. Note that conservation tends to cluster around coding regions (exons).

 

Comparative genomics exploits both similarities and differences in the proteins, RNA, and regulatory regions of different organisms to infer how selection has acted upon these elements. Those elements that are responsible for similarities between different species should be conserved through time (stabilizing selection), while those elements responsible for differences among species should be divergent (positive selection). Finally, those elements that are unimportant to the evolutionary success of the organism will be unconserved (selection is neutral).

One of the important goals of the field is the identification of the mechanisms of eukaryotic genome evolution. It is however often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. For this reason comparative genomics studies of small model organisms (for example the model Caenorhabditis elegans and closely related Caenorhabditis briggsae) are of great importance to advance our understanding of general mechanisms of evolution.

Methods

Computational approaches to genome comparison have recently become a common research topic in computer science. A public collection of case studies and demonstrations is growing, ranging from whole genome comparisons to gene expression analysis. This has increased the introduction of different ideas, including concepts from systems and control, information theory, strings analysis and data mining. It is anticipated that computational approaches will become and remain a standard topic for research and teaching, while multiple courses will begin training students to be fluent in both topics.

Tools

Computational tools for analyzing sequences and complete genomes are developing quickly due to the availability of large amount of genomic data. At the same time, comparative analysis tools are progressed and improved. In the challenges about these analyses, it is very important to visualize the comparative results.

Visualization of sequence conservation is a tough task of comparative sequence analysis. As we know, it is highly inefficient to examine the alignment of long genomic regions manually. Internet-based genome browsers provide many useful tools for investigating genomic sequences due to integrating all sequence-based biological information on genomic regions. When we extract large amount of relevant biological data, they can be very easy to use and less time-consuming.

• UCSC Browser: This site contains the reference sequence and working draft assemblies for a large collection of genomes.
• Ensembl: The Ensembl project produces genome databases for vertebrates and other eukaryotic species, and makes this information freely available online.
• MapView: The Map Viewer provides a wide variety of genome mapping and sequencing data.
• VISTA is a comprehensive suite of programs and databases for comparative analysis of genomic sequences. It was built to visualize the results of comparative analysis based on DNA alignments. The presentation of comparative data generated by VISTA can easily suit both small and large scale of data.
• BlueJay Genome Browser: a stand-alone visualization tool for the multi-scale viewing of annotated genomes and other genomic elements.

An advantage of using online tools is that these websites are being developed and updated constantly. There are many new settings and content can be used online to improve efficiency.

Applications

Agriculture

Agriculture is a field that reaps the benefits of comparative genomics. Identifying the loci of advantageous genes is a key step in breeding crops that are optimized for greater yield, cost-efficiency, quality, and disease resistance. For example, one genome wide association study conducted on 517 rice landraces revealed 80 loci associated with several categories of agronomic performance, such as grain weight, amylose content, and drought tolerance. Many of the loci were previously uncharacterized. Not only is this methodology powerful, it is also quick. Previous methods of identifying loci associated with agronomic performance required several generations of carefully monitored breeding of parent strains, a time consuming effort that is unnecessary for comparative genomic studies.

Medicine

The medical field also benefits from the study of comparative genomics. Vaccinology in particular has experienced useful advances in technology due to genomic approaches to problems. In an approach known as reverse vaccinology, researchers can discover candidate antigens for vaccine development by analyzing the genome of a pathogen or a family of pathogens. Applying a comparative genomics approach by analyzing the genomes of several related pathogens can lead to the development of vaccines that are multiprotective. A team of researchers employed such an approach to create a universal vaccine for Group B Streptococcus, a group of bacteria responsible for severe neonatal infection. Comparative genomics can also be used to generate specificity for vaccines against pathogens that are closely related to commensal microorganisms. For example, researchers used comparative genomic analysis of commensal and pathogenic strains of E. coli to identify pathogen specific genes as a basis for finding antigens that result in immune response against pathogenic strains but not commensal ones. In May of 2019, using the Global Genome Set, a team in the UK and Australia sequenced thousands of globally-collected isolates of Group A Streptococcus, providing potential targets for developing a vaccine against the pathogen, also known as S. pyogenes.

Research

Comparative genomics also opens up new avenues in other areas of research. As DNA sequencing technology has become more accessible, the number of sequenced genomes has grown. With the increasing reservoir of available genomic data, the potency of comparative genomic inference has grown as well. A notable case of this increased potency is found in recent primate research. Comparative genomic methods have allowed researchers to gather information about genetic variation, differential gene expression, and evolutionary dynamics in primates that were indiscernible using previous data and methods. The Great Ape Genome Project used comparative genomic methods to investigate genetic variation with reference to the six great ape species, finding healthy levels of variation in their gene pool despite shrinking population size. Another study showed that patterns of DNA methylation, which are a known regulation mechanism for gene expression, differ in the prefrontal cortex of humans versus chimps, and implicated this difference in the evolutionary divergence of the two species.

Dream To Live By (Published in ANALOG SCIENCE FICTION AND FACT, October 1997)

“I’m not sure how to explain this, but ...”

He tried. He showed me the device. “Don’t ask me how it works, though. I’m an engineer, not a physicist. I didn’t even build it. Found it. All I know is how to make it send me where I want to go. Excuse me, when I want to go.”

The crazy thing was, I wasn’t scared. I mean, what if someone materialized out of thin air right in front of you? Especially if it were very late a night and you were alone? I don’t know; maybe I figured that somebody who could do that could do any thing he please, so what was the point of being scared? I he wanted me dead – or whatever – I’d be that way. So I wasn’t scared.

And like I said, he tried to explain. Someone who means you harm doesn’t usually do that. But it was all hopeless. Time travel is one of those things that just can’t be, according to the way my mind works. It’s like ghosts: even if I saw one with my own eyes, I probably still wouldn’t believe it. I’m just not the sort of person who can believe things like that.

Then he told me who he was, and I really didn’t believe it. Jesus Christ, he was an old man, for crying out loud. And me, I was – am – just a kid. Who can’t even think of himself as being old, for God’s sakes. So how was I supposed to … ?

“Forget it, then. I didn’t come here to talk about dumb things, like time paradoxes and the nature of reality. I’m here for something more important than that. Come on, I’ll show you.”

He took off across the dunes. That was also eerie, the way he knew which direction to do. Ever since my folks bought our summer house home three years ago, I’d been taking these nightly strolls along the beach when I can’t sleep, which is often. There’s something about the salt air (excuse me, dimethyl sulfide laden air) and the rush and crash of waves and the rustle of grasses in the sand from the breeze, in the darkness that thrills me me, that opens my mind to things that seem impossible by day. But how the hell did he know that? Unless he really was – I shook my head and took off in a trot to catch up with him.

“If you didn’t build it then where’d you get it?” I demanded when I got to him, and once my breathing had calmed down – that’s another thing about the strolls, it helps my asthma (though the doctors didn’t know why). “And don’t tell me you bought it at a store, or some bullshit like that.” I didn’t need to be told that, obviously.

“I told you, I sound it.” He stopped for a few moments, a little winded himself. At his age, who wouldn’t be: then I realized, maybe it was more than just age, maybe it really was some of me coming through – “Don’t ask me that,” he shot back at me. “That I’m sure as hell not going to tell you.” The he chuckled, as though at some private joke. “I don’t know; maybe some careless traveler left it behind. Or maybe I was supposed to find it, so I could come here and do what I’m doing.” He shrugged. “More dumb stuff. You might as well ask why any of us are here, or what’s the meaning of life. Ah, here we are.”

We’d reached the apex of the highest dune, and were now looking down of the southeastern edge of the bay. It, as always, was a pretty sight; a waning, three-quarter’s moon was rising right over the black waters, sending a dancing rope of yellow light across the waters right to the shoreline. A bright star hovered just a couple of degrees over her, and diamond atop a pearl.

“It is beautiful, seeing it again,” he said wistfully. I thought I caught some tears at the corners of his eyes, but maybe it was just the way the moonlight was reflecting from them. “I can see why … “ He shook his head again. “Of course, from here, it’s so small.” The he also chuckled again. “Of course, from there we’re even tinier.

“Come one, sit down. Take a load off an old man’s legs.”

So we sat in the sandy grass. I felt the night moisture seep into my trousers, the way it had the last hundred times I’d been here. And damn if the old guy didn’t like it as much as I did, his arms wrapped around his knees, his heels dug into the ground. Spooky as hell.

And, believe it or not, we sat like that for a long time, just gazing into space and feeling that coolness and saying nothing. Which is also crazy, I know, but it was like he had me hymnotized or something. I mean, he really just could not be what and who he claimed to be, but I knew what I’d seen and was seeing and if there were a better explanation for it I couldn’t think of it, sitting there like that. I just couldn’t think of a single thing to say or do.

“Look,” he finally broke the spell, at just about the time I couldn’t take it any more. “I just want you to know one thing before I begin. And that is – you’re not nuts. Understand that? You’re not. I’m not saying there isn’t such a thing as being nuts – believe me, there is, as you’re going to find out soon enough – but it’s got nothing to do with you. Not now, and not ever. Understand?”

He was staring at me hard as he spoke those words. Hard the way, the way my father did, when he wanted to make sure I got his point. Genetics? I swallowed. “Yes, sir.”

“Sir?” His eyes rolled skyward. “OK. No problem. Call me sir if it makes you feel more comfortable about this. Actually, people don’t show respect like that much anymore. Maybe they should.”

“But I’m getting off the subject. Bad habit I’ve gotten into since I retired, I’m afraid. Retirement gives you too much time to … “ He grinned. “Piss away. Shit, this isn’t easy.”

A shock went up my spine; no adult had ever used a word like that in my presence, at least not so carelessly. I made me – well, maybe not exactly start to believe, but at least wonder. To the point I had to ask. “I’m really your grandfather?”

“You want a DNA analysis or something? No, don’t answer that; I shouldn’t have said it. Look, maybe if I tell you what I retired from it’ll make thinks easier. See that point of light above the moon?” He gestured skyward, at the gleam I’d noticed earlier. “Well, that’s the planet Jupiter. That’s where I worked. Well, of course not on Jupiter itself; we were actually in orbit around Europa, one of the big moons. But that’s not important. What is important is what I was doing there. You know what that was? Building the first interstellar space ship. That’s right, the first ship to go to the stars. There. How does that grab you?”

I don’t know what made me say it. I guess it was just too much for me to grasp all at once. But looking back, it was a pretty stupid thing to say. “It grabs me just fine, I guess.”

“You guess? You guess? Jesus Christ Almighty! Don’t you have any idea ... we’re going to the stars, boy! To the stars!”

That’s really the way he said it. You should have seen his face then: it was all lit up, as lit up as the moon before us. I swear, you could have read by the light of his face. All of which, again, I know should have made me scared, but it didn’t. In fact, I really didn’t know how to react. I guess it was just too big a thing for my mind, at least at that moment. The stars? He might as well about going to the – the – well, about going to the stars.

And then the strangest thing happened. OK, a lot of strange things happened that night, but in my mind this was the strangest. Damn if the old guy didn’t look at me – directly at me, into my eyes, into my soul, whatever is in me that is me – as if he understood exactly what was going on inside me. And then he touched me. He put a hand on my shoulder, squeezed a little, then patted me before letting go. His eyes were full of understanding. And, though I did comprehend why at that moment, pity as well. Which finally did scare me, a little.

“Sorry,” he said. “You have to understand. I can’t tell you too much; you could do things with that knowledge that … and the worst thing is, you’d do them from the best of intentions. That’s – part of what makes this so hard.

“But you’ve got to know something to get by. So I’m going to tell you some stuff. But – and no shitting me here, you have to promise this and keep your promise like you’ve done before in your life. I mean, even though you’re still a kid. Because this is serious stuff. You can’t tell anybody about it, for one thing. Nobody. Understand? No one else can ever know.”

He went on and on about how important it was to keep my mouth shut, but it wasn’t necessary because I’d already decided that. And not because people would think I was crazy, because I’m smart enough to know that if you know the future you can prove it; you can bet on who’s going to win the World serious and things like that. But I’m also smart enough to know why you shouldn’t. If people really are going to go to the stars, I’m sure as hell not going to mess that up.

I guess my sincerity showed through, too, because finally he stopped and nodded his head. “OK. This is – what? The late 1950s? Let’s start by telling you that there’ll be men on the moon in a little over ten years.”

Ten years? I nearly gaggedin disbelief. For Christ’s sakes.

But my reaction didn’t phase him at all. “That’s right, ten years. The next president of the United States will whip up public enthusiasm for a crash program, and we’ll do it – well, pretty much – like he’ll say we will. More or less; nothing ever works out exactly as planned – you know, Murphy’s Law and all that. But we’ll do it, almost right on schedule, just like he said. Er, says.”

He stopped for a moment and let me work on that. I gazed out again, into space, at that world hanging in the sky which looked so close and yet so impossibly far away at the same time. I felt like a baby just learning how to walk being told he was about to leap across the Grand Canyon. I mean, the moon … just the though still makes me dizzy. “Wow.”

He gave me that look again and grinned. “Knew you’d like hearing that part.” Then his face got sober, and I mean really sober. Scary sober. “Now the part you won’t like. You see, you won’t care very much when it happens. “Because while it is happening you’re going to be hiding in a jungle halfway around the world, trying not to get your brains blown out.” He let me work on that too, and for longer this time. “Oh, you’ll survive. A lot of your buddies though – guys you really care about, like brothers – won’t, but you will. And that will mess with your head for a long time, because you’ll wonder why they died and you didn’t; but like I said, that’s just dumb stuff. I told you, we’re going to the stars, and that’s the thing you want to keep in mind, no matter what happens.”

Again that look, just like before, only this time he kept his hands to himself. Then a sort of weird, half grin arose on his face; no a grin of amusement, but of something else – irony, I think they call it. “You’re probably wondering why I’m telling you this, especially after saying I couldn’t tell much at all,” accompanied the grin. “Part is because you told me I would, of course. But that’s not the real reason.”

“It isn’t?” I tried not to tremble when I asked that, but the shivering came through despite my best efforts. I mean, Jesus, why he just said to me…

“No.” He started to explain, then thought some. “You see, being through a war isn’t the worst thing that’s going to happen to you. I said we’ll go to the moon. But then – then we’ll pretty much stop. No more lunar landings, no pushing on to other planets, building space colonies, or any of the other things a lot of us thought we’d do. Oh, we’ll still have manned space missions, but they’ll be routine stuff; the only missions to other worlds will be unmanned probes – very clever probes, but unmanned nonetheless. And the politicians will cut back on the space budget more and more every year. And worst of all, hardly anybody will do anything to stop it – oh, some daring entrepreneurial types will make some waves, but that’ll be about it.

“All of which is going to be unbearable to you. See, you don’t know it yet, boy – excuse me, grandpa – but you’ve got the soul of a dreamer inside you. I knew that growing up and listening to your stories about Apollo--” he bit his lip, as though he’d said something he knew he shouldn’t “-- and those heady days of humans first getting their feet off this planet and all that. The way your face would light up up whenever you talked about it. But even if I hadn’t, I could tell it now, jst looking at you. “It’s in your eyes. The way you seem to see beyond whatever mundane things are in front of you at the moment.

“That’s why the end of the Moon missions is going to be so hard on you. You’ll barely be back from Nam – that’s what you’ll call the place where the war will be – when not only will you realize that all that fighting for your country was just a scam, but that your country was throwing away its future too. That your buddies died for nothing. That’s when … when … there’s no nice way to put it: that’s when you’ll crack up. End up in a rehab. On dope and suicidal.”

He looked apologetic, telling me all this, which, more than anything, told me he was telling the truth. Which made me start to cry, at least on the inside …

“Sorry to be telling you these things,” he said. “But they’re going to happen whether I tell you or not, so you might as well know. Besides, and now you’re got to understand, this is the real point of my being here: believe me, I wouldn’t take the chance, screwing with history like this, if it weren’t so important.

“See, you survive all that too. Because, at least it’s what I believe, you did know. Because I had come back and told you all that’s going to happen, and that it was going to turn out all right in the end.”

But it was too late for comfort. “All right? All right?!” I tell you, I’ve never raised voice at an adult, and I hope to God I never do it again because it felt so awful – screaming at an old man with all my strength. And didn’t care. “God damn you! How can you come here and tell me all this, and then say it’s all right! It’s the most horrible thing I’ve heard in my life! Jesus Christ; I wish I were dead right now. I wish ...”

It was my chance to go on and on, and I really let him have it, with all the cursing I could think of between the tears that were flowing freely from my eyes; until I was bawling incoherently, to nobody and everybody in particular and the hell with everything and everybody but mostly I just wanted to kill the old bastard, even if her really was my grandson. Shit. Fuck.

And here’s the – OK, the second strangest thing. He just sat there and took it. Try to imagine what you would happen if you went after an adult that way, but that’s not what happened at all. He wasn’t even mad. No, it was weirder than that: he actually seemed scared himself, as though he were the kid being bawled at and me the adult. He even looked on the edge of crying himself.

Which was good, because it calmed me down and let me think: we’re going to the stars, remember? And that gave him the chance to pull himself together and tell me the rest. “Jump ahead about forty years from the end of Apollo – the moon missions. People start talking about going to other worlds again: this time, Mars. Problem is, it sounds hopeless: a bunch of experts get together and calculated it will take a few hundred billion dollars, all of which nobody, not even most space enthusiasts, wants to do.

“But then along comes people like Bob Zubrin and Elon Musk, who show it can be done at about a tenth of that price, and within a decade. And well, never mind mind the details – like I said, nothing ever works exactly according to plan – but eventually we do it. And by we, I mean all of humanity – the French, Chinese, Russians, Japanese … I can’t remember all of them, but those were the major players, along with a host of others. We got to Mars and set up a permanent station, then a real colony, then … then the whole thing just took off. Back to the moon, the asteroids, then the outer planets ...” He sighed wistfully. “I wish I could tell you everything. Especially as --”

He stopped there, quite suddenly. But it was too late, for I already knew why. “Especially as I won’t be around to see it, you mean,” I finished the statement for him.

He fought for a few seconds before conceding with a nod. “Yes. But you’ll see enough. That’s why I’m here, telling you. You’ve got to get through the hard times, and you won’t if you don’t know this. Besides, you don’t have to see it to know it will happen. Besides, you don’t have to see it to know it’ll happen. Hey, I won’t see us get to the stars, but I know it will happen; which is what got me through my hard times.”

There was that twinkle in his eye again when he said that. And this time, when he looked up at the sky, it was not at the moon or Jupiter but someplace else; someplace I couldn’t make out because if there were any stars there they were too dim for me to see.

I knew he was inviting the question; hell, daring me to ask it. “How do you know?”

The answer was so obvious I should have guessed it. He pulled out the device and cradled it in his hands. “What do you think I do with this thing when I get back? Toss it out?” He shook his head. “You see, my grandchild is going to be on that first star ship. Your great-great-granddaughter. And I know she’s going to make it because when I was your age I had a visit like the one you’re having now. And let me tell you, if you think what I’ve told you is hard to believe … that I wish I could tell you. But she told me I couldn’t, because of what she said her granddaughter told her.

“But I’ve already said more than I should.” He struggled to his feet, in that slow, deliberate way older people do, not like it’s so hard but like they have to do it just right, and methodically brushed the sand off his trousers. “It’s time I should be getting back.” He put a hand out when I leapt to my feet to protest. “It’s been a pleasure meeting you, grandfather,” he cut me off. “Especially from such a different perspective than the one I remember.”

“But – “

That was as far as I got, however. He took a few steps back, touched the device, and faded into nothingness the same way he’d appeared, leaving me in my dark solitude. I started to shout something, as though my voice could carry across the decades, but caught to foolishness of that in time. He was gone. I’d never see him again until … well, until I was the elder and he the child with so much future ahead of him. If, that was, I believed any of what happened this night.

I stood there for a while longer, trying to take it all in, to make sense of what I’d just experienced. I finally decided that the only explanation that made any sense was that I’d fallen asleep out here on the dunes and dreamed the whole thing. But of course I didn’t really believe that for one moment; how could I have …. ?

Didn’t matter, though. I mean, in a few years I’ll know the truth, but standing there, gazing at those distant worlds and what lay beyond them, I realized that none of what had just happened had to be true to mean something. You see, even if it is just a dream, it’s a dream I can live by. And sometimes that’s all a person needs to keep going. Even for a kid.

Especially when the dream is real.

Alan Watts

From Wikipedia, the free encyclopedia

 

Alan Watts
Born	Alan Wilson Watts 6 January 1915 Chislehurst, London, England
Died	16 November 1973 (aged 58) Mount Tamalpais, California, US
Nationality	British
Alma mater	Seabury-Western Theological Seminary
Notable work	The Way of Zen (1957)
Spouse(s)	Eleanor Everett (m. 1938; div. 1949) Dorothy DeWitt (m. 1950; div. 1963) Mary Jane Yates King (m. 1964)
Era	Contemporary philosophy
School	Zen Buddhism Hinduism Pantheism Panentheism Christianity religious naturalism Taoism
Institutions	American Academy of Asian Studies
Main interests	Personal identity higher consciousness aesthetics cultural criticism public ethics individualism

Alan Wilson Watts (6 January 1915 – 16 November 1973) was a British philosopher who interpreted and popularised Eastern philosophy for a Western audience. Born in Chislehurst, England, he moved to the United States in 1938 and began Zen training in New York. Pursuing a career, he attended Seabury-Western Theological Seminary, where he received a master's degree in theology. Watts became an Episcopal priest in 1945, then left the ministry in 1950 and moved to California, where he joined the faculty of the American Academy of Asian Studies.

Watts gained a large following in the San Francisco Bay Area while working as a volunteer programmer at KPFA, a Pacifica Radio station in Berkeley. Watts wrote more than 25 books and articles on subjects important to Eastern and Western religion, introducing the then-burgeoning youth culture to The Way of Zen (1957), one of the first bestselling books on Buddhism. In Psychotherapy East and West (1961), Watts proposed that Buddhism could be thought of as a form of psychotherapy and not a religion. He considered Nature, Man and Woman (1958) to be, "from a literary point of view—the best book I have ever written." He also explored human consciousness in the essay "The New Alchemy" (1958) and in the book The Joyous Cosmology (1962).

Towards the end of his life, he divided his time between a houseboat in Sausalito and a cabin on Mount Tamalpais. According to the critic Erik Davis, his "writings and recorded talks still shimmer with a profound and galvanizing lucidity."

Early years

Watts aged 7

 

Watts was born to middle-class parents in the village of Chislehurst, Kent (now south-east London), on 6 January 1915, living at 3 (now 5) Holbrook Lane, which was previously lived in by author John Hemming-Clark in the early 1900s.^[4] Watts' father, Laurence Wilson Watts, was a representative for the London office of the Michelin Tyre Company. His mother, Emily Mary Watts (née Buchan), was a housewife whose father had been a missionary. With modest financial means, they chose to live in pastoral surroundings and Watts, an only child, grew up playing at brookside, learning the names of wildflowers and butterflies. Probably because of the influence of his mother's religious family the Buchans, an interest in "ultimate things" seeped in. It mixed with Watts's own interests in storybook fables and romantic tales of the mysterious Far East.

Watts also later wrote of a mystical dream he experienced while ill with a fever as a child. During this time he was influenced by Far Eastern landscape paintings and embroideries that had been given to his mother by missionaries returning from China. The few Chinese paintings Watts was able to see in England riveted him, and he wrote "I was aesthetically fascinated with a certain clarity, transparency, and spaciousness in Chinese and Japanese art. It seemed to float..." These works of art emphasised the participatory relationship of people in nature, a theme that stood fast throughout his life and one that he often wrote about.

Buddhism

By his own assessment, Watts was imaginative, headstrong, and talkative. He was sent to boarding schools (which included both academic and religious training of the "Muscular Christian" sort) from early years. Of this religious training, he remarked "Throughout my schooling my religious indoctrination was grim and maudlin."

Watts spent several holidays in France in his teen years, accompanied by Francis Croshaw, a wealthy Epicurean with strong interests in both Buddhism and exotic little-known aspects of European culture. It was not long afterward that Watts felt forced to decide between the Anglican Christianity he had been exposed to and the Buddhism he had read about in various libraries, including Croshaw's. He chose Buddhism, and sought membership in the London Buddhist Lodge, which had been established by Theosophists, and was then run by the barrister Christmas Humphreys. Watts became the organization's secretary at 16 (1931). The young Watts explored several styles of meditation during these years.

Education

Watts attended The King's School, Canterbury, next door to Canterbury Cathedral. Though he was frequently at the top of his classes scholastically and was given responsibilities at school, he botched an opportunity for a scholarship to Oxford by styling a crucial examination essay in a way that was read as "presumptuous and capricious."

When he left secondary school, Watts worked in a printing house and later a bank. He spent his spare time involved with the Buddhist Lodge and also under the tutelage of a "rascal guru" named Dimitrije Mitrinović. (Mitrinović was himself influenced by Peter Demianovich Ouspensky, G. I. Gurdjieff, and the varied psychoanalytical schools of Freud, Jung and Adler.) Watts also read widely in philosophy, history, psychology, psychiatry and Eastern wisdom. 

By his own reckoning, and also by that of his biographer Monica Furlong, Watts was primarily an autodidact. His involvement with the Buddhist Lodge in London afforded Watts a considerable number of opportunities for personal growth. Through Humphreys, he contacted eminent spiritual authors, e.g. the artist, scholar, and mystic Nicholas Roerich, Sarvapalli Radhakrishnan, and prominent theosophists like Alice Bailey. 

In 1936, aged 21, he attended the World Congress of Faiths at the University of London, heard D. T. Suzuki read a paper, and afterwards was able to meet this esteemed scholar of Zen Buddhism. Beyond these discussions and personal encounters, Watts absorbed, by studying the available scholarly literature, the fundamental concepts and terminology of the main philosophies of India and East Asia.

Influences and first publication

Watts's fascination with the Zen (or Ch'an) tradition—beginning during the 1930s—developed because that tradition embodied the spiritual, interwoven with the practical, as exemplified in the subtitle of his Spirit of Zen: A Way of Life, Work, and Art in the Far East. "Work", "life", and "art" were not demoted due to a spiritual focus. In his writing, he referred to it as "the great Ch'an (or Zen) synthesis of Taoism, Confucianism and Buddhism after 700 CE in China." Watts published his first book, The Spirit of Zen, in 1936. Two decades later, in The Way of Zen he disparaged The Spirit of Zen as a "popularisation of Suzuki's earlier works, and besides being very unscholarly it is in many respects out of date and misleading." 

Watts married Eleanor Everett, whose mother Ruth Fuller Everett was involved with a traditional Zen Buddhist circle in New York. Ruth Fuller later married the Zen master (or "roshi"), Sokei-an Sasaki, who served as a sort of model and mentor to Watts, though he chose not to enter into a formal Zen training relationship with Sasaki. During these years, according to his later writings, Watts had another mystical experience while on a walk with his wife. In 1938 they left England to live in the United States. Watts became a United States citizen in 1943.

Christian priest and after

Watts left formal Zen training in New York because the method of the teacher did not suit him. He was not ordained as a Zen monk, but he felt a need to find a vocational outlet for his philosophical inclinations. He entered Seabury-Western Theological Seminary, an Episcopal (Anglican) school in Evanston, Illinois, where he studied Christian scriptures, theology, and church history. He attempted to work out a blend of contemporary Christian worship, mystical Christianity, and Asian philosophy. Watts was awarded a master's degree in theology in response to his thesis, which he published as a popular edition under the title Behold the Spirit: A Study in the Necessity of Mystical Religion.

He later published Myth & Ritual in Christianity (1953), an eisegesis of traditional Roman Catholic doctrine and ritual in Buddhist terms. However, the pattern was set, in that Watts did not hide his dislike for religious outlooks that he decided were dour, guilt-ridden, or militantly proselytizing—no matter if they were found within Judaism, Christianity, Islam, Hinduism, or Buddhism. 

As recounted in his autobiography, Alan was ordained as an Episcopal priest in 1945 (aged 30) and resigned the ministry by 1950, partly as a result of an extramarital affair which resulted in his wife having their marriage annulled, but also because he could no longer reconcile his Buddhist beliefs with the formal doctrine of the church. He spent the New Year getting to know Joseph Campbell and Campbell's wife, Jean Erdman, as well as the composer John Cage. 

In early 1951, Watts moved to California, where he joined the faculty of the American Academy of Asian Studies in San Francisco. Here he taught from 1951 to 1957 alongside Saburō Hasegawa (1906–1957), Frederic Spiegelberg, Haridas Chaudhuri, lama Tada Tōkan (1890–1967), and various visiting experts and professors. Hasegawa, in particular, served as a teacher to Watts in the areas of Japanese customs, arts, primitivism, and perceptions of nature. It was during this time he met the poet, Jean Burden with whom he had a four-year love affair.

Alan credited her as an "important influence" in his life and gave her dedicatory cryptograph in his book "Nature, Man and Woman", to which he alludes in his autobiography (p. 297). Besides teaching, Watts served for several years as the Academy's administrator. One notable student of his was Eugene Rose, who later went on to become a noted Orthodox Christian hieromonk and controversial theologian within the Orthodox Church in America under the jurisdiction of ROCOR. Rose's own disciple, a fellow monastic priest published under the name Hieromonk Damascene, produced a book entitled Christ the Eternal Tao, in which the author draws parallels between the concept of the Tao in Chinese philosophy and the concept of the Logos in classical Greek philosophy and Eastern Christian theology. 

Watts also studied written Chinese and practiced Chinese brush calligraphy with Hasegawa as well as with some of the Chinese students who enrolled at the academy. While Watts was noted for an interest in Zen Buddhism, his reading and discussions delved into Vedanta, "the new physics", cybernetics, semantics, process philosophy, natural history, and the anthropology of sexuality.

Middle years

Watts left the faculty for a career in the mid-1950s. In 1953, he began what became a long-running weekly radio program at Pacifica Radio station KPFA in Berkeley. Like other volunteer programmers at the listener-sponsored station, Watts was not paid for his broadcasts. These weekly broadcasts continued until 1962, by which time he had attracted a "legion of regular listeners".

Watts continued to give numerous talks and seminars, recordings of which were broadcast on KPFA and other radio stations during his life. These recordings are broadcast to this day. For example, in 1970 Watts lectures were broadcast on Sunday mornings on San Francisco radio station KSAN; and even today a number of radio stations continue to have an Alan Watts program in their weekly program schedules. Original tapes of his broadcasts and talks are currently held by the Pacifica Radio Archives, based at KPFK in Los Angeles, and at the Electronic University archive founded by his son, Mark Watts. 

In 1957 Watts, then 42, published one of his best known books, The Way of Zen, which focused on philosophical explication and history. Besides drawing on the lifestyle and philosophical background of Zen, in India and China, Watts introduced ideas drawn from general semantics (directly from the writings of Alfred Korzybski) and also from Norbert Wiener's early work on cybernetics, which had recently been published. Watts offered analogies from cybernetic principles possibly applicable to the Zen life. The book sold well, eventually becoming a modern classic, and helped widen his lecture circuit. 

In 1958, Watts toured parts of Europe with his father, meeting the Swiss psychiatrist Carl Jung and the German psychotherapist Karlfried Graf Dürckheim.

Upon returning to the United States, Watts recorded two seasons of a television series (1959–1960) for KQED public television in San Francisco, "Eastern Wisdom and Modern Life".

In the 1960s, Watts became increasingly interested in how identifiable patterns in nature tend to repeat themselves from the smallest of scales to the most immense. This became one of his passions in his research and thought.

Though never affiliated for long with any one academic institution, he was Professor of Comparative Philosophy at the California Institute of Integral Studies (as mentioned above), had a fellowship at Harvard University (1962–1964), and was a Scholar at San Jose State University (1968). He also lectured to many college and university students as well as the general public. His lectures and books gave him far-reaching influence on the American intelligentsia of the 1950s–1970s, but he was often seen as an outsider in academia. When questioned sharply by students during his talk at University of California, Santa Cruz, in 1970, Watts responded, as he had from the early sixties, that he was not an academic philosopher but rather "a philosophical entertainer".

Experimentation

Some of Watts' writings published in 1958 (e.g., his book Nature, Man and Woman and his essay "The New Alchemy") mentioned some of his early views on the use of psychedelic drugs for mystical insight. Watts had begun to experiment with psychedelics, initially with mescaline given to him by Oscar Janiger. He tried LSD several times in 1958, with various research teams led by Keith S. Ditman, Sterling Bunnell Jr., and Michael Agron. He also tried marijuana and concluded that it was a useful and interesting psychoactive drug that gave the impression of time slowing down. Watts' books of the '60s reveal the influence of these chemical adventures on his outlook.

He later said about psychedelic drug use, "If you get the message, hang up the phone. For psychedelic drugs are simply instruments, like microscopes, telescopes, and telephones. The biologist does not sit with eye permanently glued to the microscope, he goes away and works on what he has seen."

For a time, Watts came to prefer writing in the language of modern science and psychology (such as Psychotherapy East and West), finding a parallel between mystical experiences and the theories of the material universe proposed by 20th-century physicists. He later equated mystical experience with ecological awareness, and typically emphasized whichever approach seemed best suited to the audience he was addressing.

Applied aesthetics

Watts sometimes ate with his group of neighbors in Druid Heights (near Mill Valley, California) who had endeavored to combine architecture, gardening, and carpentry skills to make a beautiful and comfortable life for themselves. These neighbors accomplished this by relying on their own talents and using their own hands, as they lived in what has been called "shared bohemian poverty". Druid Heights was founded by the writer Elsa Gidlow, and Watts dedicated his book The Joyous Cosmology to the people of this neighborhood. He later dedicated his autobiography to Elsa Gidlow, for whom he held a great affection. 

Regarding his intentions, Watts attempted to lessen the alienation that accompanies the experience of being human that he felt plagued the modern Westerner, and (like his fellow British expatriate and friend, Aldous Huxley) to lessen the ill will that was an unintentional by-product of alienation from the natural world. He felt such teaching could improve the world, at least to a degree. He also articulated the possibilities for greater incorporation of aesthetics (for example: better architecture, more art, more fine cuisine) in American life. In his autobiography he wrote, "… cultural renewal comes about when highly differentiated cultures mix".

In his last novel, Island (1962), Aldous Huxley mentions the religious practice of maithuna as being something like what Roman Catholics call "coitus reservatus". A few years before, Watts had discussed the theme in his own book, Nature, Man and Woman, in which he discusses the possibility of the practice being known to early Christians and of it being kept secretly by the Church.

Later years

In his writings of the 1950s, he conveyed his admiration for the practicality in the historical achievements of Chán (Zen) in the Far East, for it had fostered farmers, architects, builders, folk physicians, artists, and administrators among the monks who had lived in the monasteries of its lineages. In his mature work, he presents himself as "Zennist" in spirit as he wrote in his last book, Tao: The Watercourse Way. Child rearing, the arts, cuisine, education, law and freedom, architecture, sexuality, and the uses and abuses of technology were all of great interest to him. 

Though known for his discourses on Zen, he was also influenced by ancient Hindu scriptures, especially Vedanta. He spoke extensively about the nature of the divine reality which Man misses: how the contradiction of opposites is the method of life and the means of cosmic and human evolution, how our fundamental Ignorance is rooted in the exclusive nature of mind and ego, how to come in touch with the Field of Consciousness and Light, and other cosmic principles. These are discussed in great detail in dozens of hours of audio that are in part captured in the 'Out of Your Mind' series. 

Watts sought to resolve his feelings of alienation from the institutions of marriage and the values of American society, as revealed in his classic comments on love relationships in "Divine Madness" and on perception of the organism-environment in "The Philosophy of Nature". In looking at social issues he was quite concerned with the necessity for international peace, for tolerance and understanding among disparate cultures.

Watts also came to feel acutely conscious of a growing ecological predicament. Writing, for example, in the early 1960s: "Can any melting or burning imaginable get rid of these ever-rising mountains of ruin—especially when the things we make and build are beginning to look more and more like rubbish even before they are thrown away?" These concerns were later expressed in a television pilot made for NET (National Educational Television) filmed at his mountain retreat in 1971 in which he noted that the single track of conscious attention was wholly inadequate for interactions with a multi-tracked world.

Death

In October 1973, Watts returned from a European lecture tour to his cabin in Druid Heights, California. Friends of Watts had been concerned about him for some time over what they considered his alcoholism. On 16 November 1973, at age 58, he died in his sleep. He was reported to have been under treatment for a heart condition. His body was cremated very shortly thereafter. His ashes were split, with half buried near his library at Druid Heights and half at the Green Gulch Monastery.

A personal account of Watts' last years and approach to death is given by Al Chung-liang Huang in Tao: The Watercourse Way. His son Mark Watts has prepared a biographical documentary that details questions surrounding his father's death and performed ritual cremation on a nearby beach. His father's ashes were returned to the cabin where he had died.

Views

On spiritual and social identity

In regards to his ethical outlook, Watts felt that absolute morality had nothing to do with the fundamental realization of one's deep spiritual identity. He advocated social rather than personal ethics. In his writings, Watts was increasingly concerned with ethics applied to relations between humanity and the natural environment and between governments and citizens. He wrote out of an appreciation of a racially and culturally diverse social landscape.

He often said that he wished to act as a bridge between the ancient and the modern, between East and West, and between culture and nature. 

Watts led some tours for Westerners to the Buddhist temples of Japan. He also studied some movements from the traditional Chinese martial art taijiquan, with an Asian colleague, Al Chung-liang Huang.

Worldview

In several of his later publications, especially Beyond Theology and The Book: On the Taboo Against Knowing Who You Are, Watts put forward a worldview, drawing on Hinduism, Chinese philosophy, pantheism or panentheism, and modern science, in which he maintains that the whole universe consists of a cosmic Self playing hide-and-seek (Lila); hiding from itself (Maya) by becoming all the living and non-living things in the universe and forgetting what it really is – the upshot being that we are all IT in disguise. In this worldview, Watts asserts that our conception of ourselves as an "ego in a bag of skin," or "skin-encapsulated ego" is a myth; the entities we call the separate "things" are merely aspects or features of the whole. 

Watts' books frequently include discussions reflecting his keen interest in patterns that occur in nature and which are repeated in various ways and at a wide range of scales – including the patterns to be discerned in the history of civilizations.

Supporters and critics

Watts's explorations and teaching brought him into contact with many noted intellectuals, artists, and American teachers in the human potential movement. His friendship with poet Gary Snyder nurtured his sympathies with the budding environmental movement, to which Watts gave philosophical support. He also encountered Robert Anton Wilson, who credited Watts with being one of his "Light[s] along the Way" in the opening appreciation of Cosmic Trigger. Werner Erhard attended workshops given by Alan Watts and said of him, "He pointed me toward what I now call the distinction between Self and Mind. After my encounter with Alan, the context in which I was working shifted."

Watts has been criticized by Buddhists such as Philip Kapleau and D. T. Suzuki for allegedly misinterpreting several key Zen Buddhist concepts. In particular, he drew criticism from those who believe that zazen must entail a strict and specific means of sitting, as opposed to a cultivated state of mind available at any moment in any situation. Typical of these is Kapleau's claim that Watts dismissed zazen on the basis of only half a koan.

In regard to the aforementioned koan, Robert Baker Aitken reports that Suzuki told him, "I regret to say that Mr. Watts did not understand that story." In his talks, Watts addressed the issue of defining zazen practice by saying, "A cat sits until it is tired of sitting, then gets up, stretches, and walks away", and referring to Zen master Bankei: "Even when you're sitting in meditation, if there's something you've got to do, it's quite all right to get up and leave".

Watts's biographers saw him, after his stint as an Anglican priest, as representative of no religion but as a lone-wolf thinker and social rascal. In David Stuart's warts-and-all biography of the man, Watts is seen as an unusually gifted speaker and writer driven by his own interests, enthusiasms, and demons. Elsa Gidlow, whom Alan called "sister", refused to be interviewed for this work but later painted a kinder picture of Alan's life in her own autobiography, Elsa, I Come With My Songs.

However, Watts did have his supporters in the Zen community, including Shunryu Suzuki, the founder of the San Francisco Zen Center. As David Chadwick recounted in his biography of Suzuki, Crooked Cucumber: the Life and Zen Teaching of Shunryu Suzuki, when a student of Suzuki's disparaged Watts by saying "we used to think he was profound until we found the real thing", Suzuki fumed with a sudden intensity, saying, "You completely miss the point about Alan Watts! You should notice what he has done. He is a great bodhisattva."

Personal life

Watts married three times and had seven children (five daughters and two sons). Watts met Eleanor Everett in 1936, when her mother, Ruth Fuller Everett, brought her to London to study piano. They met at the Buddhist Lodge, were engaged the following year and married in April 1938. A daughter, Joan, was born in November 1938 and another, Anne, was born in 1942. Their marriage ended in 1949, but Watts continued to correspond with his former mother-in-law. In 1950, Watts married Dorothy DeWitt. He moved to San Francisco in early 1951 to teach. They began a family that grew to include five children: Tia, Mark, Richard, Lila, and Diane. The couple separated in the early 1960s after Watts met Mary Jane Yates King (called "Jano" in his circle) while lecturing in New York. After a difficult divorce he married King in 1964. The couple divided their time between Sausalito, California, where they lived on a houseboat called the Vallejo, and a secluded cabin in Druid Heights, on the southwest flank of Mount Tamalpais north of San Francisco. Some regard Watts as having been an unfaithful husband and a poor father.

Watts' eldest daughters, Joan and Anne, own and manage most of the copyrights to his books. His son, Mark, serves as curator of his father's audio, video and film and has published content of some of his spoken lectures in print format. 

Jean Burden, his lover and the inspiration/editor of Nature, Man and Woman, remained in his thoughts to the end of his life. 

Watts was a heavy smoker throughout his life and in his later years drank heavily.