How many RNA molecules per cell are needed for function?

One of the issues in the junk DNA wars is the importance of all those RNAs that are detected in sensitive assays. About 90% of the human genome is complementary to RNAs that are made at some time in some tissue or other. Does this pervasive transcription mean that most of the genome is functional or are most of these transcripts just background noise due to accidental transcription?

Jerry Coyne retires

We knew this was coming but it's still a noteworthy event [I retire today].

I like what Jerry Coyne says about his career, so far, but one particular section caught my eye.

Several years ago, I began to realize that my job as a scientist and academic was not as challenging as it had been for the previous 35 years. I had mastered the requisites of such a job: doing research, writing papers, mentoring and teaching students, getting grants, and so on. The one challenge left was discovering new things about evolution, which was the really exciting thing about science. I’ve always said that there is nothing comparable to being the first person to see something that nobody’s seen before. Artists must derive some of the same satisfaction when creating new fictional worlds, or finding new ways to see the existing world, but it is only those who do science—and I mean “science” in the broad sense—who are privileged to find and verify new truths about our cosmos.

But finding truly new things—things that surprise and delight other scientists—is very rare, for science, like Steve Gould’s fossil record, is largely tedium punctuated by sudden change. And so, as I began to look for more sustaining challenges; I slowly ratcheted down my research, deciding that I’d retire after my one remaining student graduated. That decision was made two years ago, but the mechanics of retirement—and, in truth, my own ambivalence—have led to a slight delay. Today, though, is the day.

For me, the pace of discovery in the lab was far too slow. Yes, it's true that you can be the very first person ever to see something that nobody has ever seen before but those "somethings" are often trivial. I learned that there was a heck of a lot that I didn't know but other people did. Furthermore, I needed to know all that stuff before I could really interpret my own lab results.

It was far more efficient, and far more exciting, for me to learn facts and information from others than to try and discover something truly important in my own lab.

That's why I decided to concentrate on writing, especially biochemistry textbooks. It was my opportunity to learn about everything and my opportunity to teach others about what was important and what was not important. It was my opportunity to think about biochemistry and evolution. That was much more satisfying, intellectually, than the tedium of everyday lab work. I was cocky enough to believe that I, personally, could contribute more to science through theory (and teaching) than through working at the bench.

As it turned out, I found far more ways of "seeing the existing world," as Jerry puts it, though reading, thinking, and teaching than I ever did by cloning a gene and studying its expression. So far, none of those ways are terribly original but they're at least new to me. And many of them are new to all the people around me who I keep pestering whenever I come across something interesting.

Nowadays, the tedium of stasis in everyday science isn't the only problem facing young scientists. There's also the tedium of grant writing and the tedium (and stress) of not getting a grant to keep your lab running. Perhaps they should get out of that rat race. We need more thinking in science and not more ChIP assays or RNA-Seq experiments.

I'd like to create an Institute for Advanced Study based on the Princeton model but with an emphasis on biology. I think we need to celebrate and honor thinking biologists and not just "doers" who run megalabs churning out more ENCODE results, or the genome sequence of a new species, or the 1001st human genome sequence.

I can think of a dozen scientists who I would hire right away if I had the money. Can you imagine how exciting it would be to put them all in one place where they can interact and be creative?

Maybe I should apply for a Templeton grant?

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Stealin' All My Dreams

Canada is in the middle of a Federal election campaign. The vote is on October 19th.

Currently the Conservative Party under Stephen Harper has a majority in Parliament but the polls show a three-way race between the Conservatives, the Liberals under Justin Trudeau, and the New Democratic Party (NDP) under Thomas Mulcair.

About two-thirds of Canadians are intending to vote for anybody except the current Prime Minister (Stephen Harper). If you want to know why, listen to Blue Rodeo singing Stealin' All My Dreams.



Vote for the party in your riding that's most likely to beat the Conservatives.

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How can she go wrong?—let us count the ways ...

There's a very good reason why the creationist website Evolution News & Views (sic) doesn't allow comments but that won't stop us from making comments on Sandwalk. Check out Ann Gauger's latest offering at: Waiting for Mutations: Why Darwinism Won't Work.

There are a few errors in that post. How many? Let us count the ways.¹

Theme
Mutation
-definition
-mutation types
-mutation rates
-phylogeny
-controversies
What's interesting about that post is that we've been over the data many times in an attempt to explain mutation to the creationists. Last year I tried to explain why humans and chimpanzees have accumulated about 22 million point mutations since the time they evolved from a common ancestor about 6 million years ago. I thought it would be helpful if they understood why these numbers are perfectly reasonable according to population genetics.

What happened was that the vast majority of commenters on Uncommon Descent called me names and told me I was wrong. A few creationists, Sal Cordova, Vincent Torley, and Branko Kozulic took up the challenge and, for a short while I thought they understood.

Lessons not learned from 50 years ago

A few months ago Nature published an article on how to create a science-literate population. There's a letter in the Sept. 17th (2015) issue that addresses this point by reminding readers of another article published 50 years ago (1965).

The title of that older article was "New thinking in undergraduate education." Here's what it said ....

Students are in danger of "spending too much of their time memorizing facts, and [have] insufficient time at [their] disposal to master the principles underlying [their] subject and to develop [their] powers of thought." .... the most important purpose of a university education is to teach [students] to think for [themselves] ... it may on occasion demand a re-examination of the whole approach to a subject in undergraduate courses."

I remember that the biology department where I was an undergraduate (Carleton University in Ottawa) organized a weekend conference to discuss revising undergraduate education in 1967. I spoke about the need to focus on ideas and concepts and get away from boring lectures about facts.

plus ça change, plus c'est la même chose
UPDATE: A reader asked for the references. The letter in the Sept. 17th issue is from Barry S. Winkler [doi: 10.1038/525321f]. The original article from 1965 is in the issue of Feb. 27, 1965 [doi: 10.1038/205835a0]. The 2015 article referred to in the recent letter to Nature is Bradforth et al. (2015).

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Bradforth, S.F., Miller, E.R., Dichtel, W.R., Leibovich, A.K., Feig, A.L., Martin, J.D., Bjorkman, K.S., Schultz, Z.D., and Smith, T.L. (2015) University learning: Improve undergraduate science education. Nature 523:282-284 [PDF]

For the King gets greenlit and furry companions

My son's new game, For The King, is doing well on Kickstarter. So far they have over 1600 backers and over $78,000 [Kickstarter: For The King]. They met their launch goal within 24 hours and now they're adding stretch goals when additional support comes in.

I'm excited that they've reached $75,000 because that activates the "Furry Companions" addition to the game. You'll be familiar with the concept if you remember Hack and NetHack [see Pet - WikiHack]. You now get a pet in For The King. But be careful! Sometimes your pet can turn on you and you don't want that to happen if you have a pet dragon or a pet cockatrice.

In other news, the team has created musicians ...

As we near the inevitable Furry Companions stretch goal, we have our sites now on The Sound of Music stretch goal. The Sound of Music will add musicians and musical instruments to the game along with some potentially awesome mechanics. Primarily a support class, musicians make everyone around them better through their inspiring songs and ballads.

We'll be experimenting with some unique mechanics for this class like having them guarantee a successful slot for other party members if they successfully play an inspiring ballad. However if they miss a few notes it may have the opposite effect, so you'll have to use this ability wisely. They can potentially use the reverse of this ability against their enemies, forcing them to fail a slot. In this manner they can neutralize enemy special attacks and critical strikes if they're on key.

Different instruments will allow for different abilities so the option will also be there for them to play ballads of destruction doing AOE type damage to groups of enemies. Think Fire Lutes! We're really excited about this class and can't wait to share our ideas and progress on it with you.

I'm relieved at this description 'cause I was worried that the musicians would play the kind of music that my son used to listen to when he was growing up!

Give them more money if you want The Sound of Music. (I suspect that this stretch goal is aimed at Ms. Sandwalk and my daughter and granddaughter.)

The most exciting news is that For The King has been Greenlit. I suspect that most Sandwalk readers don't have any idea what this means. It means that the game has been accepted by the Steam community so it will be published on Steam—a fantastic gaming platform: Steam Greenlights For The King. They got voted in within 5 days!

I'm beginning to think that this game will be a success and my son and daughter-in-law won't have to move into our basement. Thanks to all Sandwalk readers who supported my son.

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Emile Zuckerkandl and the 50th anniversary of the birth of molecular evolution

Emile Zuckerkandl (1922-2013) and Linus Pauling (1901-1994) published a paper on the evolution of proteins back in 1964. The original paper was published first in a Russian translation. The English version appeared in 1965 and that paper marks the beginning of the field of molecular evolution (Zuckerkandl and Pauling, 1965a).

Dan Graur has a nice post: Happy Birthday Molecular Evolution! You’re 50 Years Old. I stole the photo from Dan's post. It shows Linus Pauling (left) and Emile Zuckerkandl (right) in Japan in 1986.

Most of you have heard of Linus Pauling—he won two Nobel Prizes—but you've probably not heard of Emile Zuckerkandl. That's a shame because he made significant contributions to the field of molecular evolution. Those early papers (Zuckerkandl and Pauling, 1965a; Zuckerkandl and Pauling, 1965b; Zuckerkandl and Pauling, 1965c) were remarkably insightful.

One of my graduate students, Sharon Shtang, was so impressed with the "Evolving Genes and Proteins" paper that she quoted from it at the beginning of her Ph.D. thesis. The authors were commenting on the, then novel, use of amino acid sequences in proteins to demonstrate evolution. They were worried that some people would think this was overkill since evolution was a well-established fact. They said ... [On Beating Dead Horses]

Some beating of dead horses may be ethical, where here and there they display unexpected twitches that look like life.

This is an obvious reference to creationism.

Café Scientifique in Mississauga

Some of you might recall that I gave a presentation last June on "Replaying the Tape of Life" at a Café Scientifique in Mississauga )(Ontario, Canada) [Café Scientifique]. It was a lot of fun and there were many interesting people.

The new season begins tomorrow with a meeting at 7 pm at The Franklin House, 263 Queen St S., in Streetsville, Mississauga (Ontario Canada) [see Meetup]. Come and join us for a discussion about science outreach ...

Come hear Randy Attwood, Executive Director of the Royal Astronomical Society of Canada, interviewed for a Star Spot podcast by host Justin Trottier.

In his interviews at the Star Spot, Mr. Trottier aims to go beyond the science under discussion to explore the implications of specific discoveries, why we explore, and how to engage the public in scientific pursuits. Where applicable The Star Spot dives into the intersection of science, philosophy and life's big questions.

Randy is Executive Director of the Royal Astronomical Society of Canada and founder of the RASC Mississauga Centre. He is co-organizer of the Mississauga Star Gazers meetup group and of the monthly Observe the Moon and planets through large telescopes event at Riverwood Conservancy. He is a frequent guest on CTV called upon to explain astronomy and space exploration news.

An Engineering Science graduate of the University of Toronto, Justin is best is a frequent guest on radio and TV programs discussing church-state separation, skeptical inquiry and fundamental freedoms. While known to many of us as the founder of Center for Inquiry Canada (CFIC) as well as of the Freethought Association of Canada, the range of his interests is very broad. He is a founder of the U of T Astronomy and Space Exploration Society and a former board member of the Canadian Space Society.

Don't be shy about joining us. There are plenty of newcomers at each meeting. All you have to do is walk upstairs at the restaurant and order your beer (and food if you're hungry)!

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Does genome size affect fitness in seed beetles?

Many of us think that the C-Value Paradox isn't really a paradox any more. We think that the variations in genome size among different species can be explained because expansion and contraction of genome size is mostly neutral with respect to evolution and thus the differing sizes of genomes in different species is explained by random genetic drift. Only a small percentage of most eukaryotic genomes is actually functional and the rest is junk. In the case of the human genome, about 90% is junk DNA.

Some scientists aren't happy with this explanation of the C-Value Paradox so they have come up with other explanations to account for the differences in genome sizes. A recent paper by Arnqvist et al. (2015) suggests that genome size affects reproductive fitness in seed beetles.

The introduction to their paper is a nice summary of the controversy ...

What does this big number mean?

There's a big number (63,000) in the windows of a biology laboratory somewhere in the world. There's also a picture of Darwin so it probably has something to do with evolution.

What could it possibly mean? Can you guess before clicking on the answer at 63,000 Strong?

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For The King: Kickstarter meets its launch goal in 24 hours!!!!

Recall that my son, Gord, and his friends Colby Young, David Lam, and Sean Hoyle [The Dev Team] formed IronOak Games to create "For The King." They need money to pay for development. I promoted their Kickstarter campaign at: Kickstarter - For The King.

I'm delighted to announce that they have met their threshold goal of $40,000. That means that all the donations will go through and the project has launched! (You need to achieve a minimum goal or none of the Kickstarter donations count.)

Gord posted a little happy dance video to celebrate.

They are now at $52,000 with over 700 backers. Because they reached the minimum goal, they have activated "stretch goals" where they can add extra features to the game. Here's what the Dev Team said in a email message to the supporters.

What a few days it’s been! First of all.....we did it! Thank you to so many people for backing us, sharing the project and showing interest! It’s really amazing, we’ve been humbled and just couldn’t be happier. An extra special thanks to our friends, family and colleagues who supported us as soon as the campaign was live, you people are awesome!

We worked immense hours as the launch date got closer and closer, fine tuning and polishing everything we could think of. It was a great feeling to hit the green Publish button, but I’m not going to lie, we were terrified. It feels really good to have people appreciate something we believe so firmly in.

The next order of business is that we already hit a mini stretch goal, The Dead Shall Rise! As a big thank you, all of our Kickstarter backers will be able to play as the adorable undead and carry on with their adventure even though death clearly came knocking a long time ago. To clarify, the undead skins are just aesthetic alternatives for our 6 core playable characters which grant no gameplay advantage whatsoever.

Looking ahead we are beginning to creep up on the Frost Realm stretch goal! I am so excited because we were forced to make some cuts from the our core set of realms and we made the hard decision of removing it. This was done not because we didn’t want it in the game but because it needs the extra attention to be everything it should be!
The Frost Realm will be a whole new biome with its own crippling weather and secluded boroughs to discover. New scourges, yetis, ice dungeons and other frozen abominations terrorizing the foolish who seek adventure. This will be a truly savage addition to Fahrul’s colorful kingdom.

I should mention that the speed at which this all unfolded blindsided us, sorry for any delays! Stretch Goal reveal will be coming shortly!

For The King!

I bought a university and a professor-sage character who gives players advice on how to win the game. Ms. Sandwalk bought a village fair with a princess who lets you win valuable prizes in the midway games. Now we have to design our characters. You will encounter them in the game!

The Frost Realm is cool¹ but I'm looking forward to the next stretch goal at $70,000. I'm not supposed to tell you what it is but here's a hint ... it's one of the most important features in Hack!

Keep donating to make the game even better.

Here's a video that I hadn't seen before. It features my son (and a few other dudes)! I'm so proud of him. He couldn't have done any of this without a business degree from McGill!

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1. Pun intended.

Philosophy and reality

The figure on the right has been circulating on Facebook. It suggests that philosophers in the Philosophy of Science are perplexed about the nature of reality. Some might actually believe that reality doesn't exist.

The diagram evokes the memory of undergraduate debates about whether that chair actually exists or whether we live in the matrix. These debates seem silly on the surface but they are actually very important in classes devoted to logic and critical thinking. They provide real experience in thinking.

For The King Kickstarter Campaign Begins

My son, Gord, and his friends Colby Young, David Lam, and Sean Hoyle [The Dev Team] formed IronOak Games. Their first game will be "For The King" and they need money to pay for development. I am shamelessly¹ promoting their Kickstarter campaign at: Kickstarter - For The King.

I'm buying a university and a professor-sage character who gives players advice on how to win the game. Ms. Sandwalk is buying a village fair with a princess who lets you win valuable prizes in the midway games.

For only $50 you can name a ghost after yourself or your favorite creationist! And for $175 you can become a dead adventurer or name one after Richard Dawkins or Stephen Jay Gould! For $500 you can become a Scourge in the game. This is ideal for the trolls who infest Sandwalk.

$15 - TRAVELER
+Digital Copy of the Game (Includes Early Access on Steam, PC or Mac)

$20 - QUEST RUNNER
+Closed Beta Access
+Backer Forum/Poll Access
+KS Exclusive PC and Phone Wallpapers
+Digital Copy of the Game (Includes Early Access on Steam, PC or Mac)

$25 - ADVENTURER (EARLY BIRD) Limited reward (250 left of 250)
-Get everything from the Adventurer Tier below at a discounted price!

$30 - ADVENTURER
Includes all rewards from the tiers below plus:
+KS Exclusive In-Game Hat Skins for each of the main characters
+Your name in credits
+Digital "Illustrated Adventuring Guide"
An experienced adventurer never leaves home without their favorite hat. Unlock hats for each of the main characters so you can adventure in style.

$40 - BANSHEE (EARLY BIRD) Limited reward (100 left of 100)
-Get all the Banshee level rewards at a discounted price

$50 - BANSHEE
Includes all rewards from the tiers below plus:
+A ghost named after you in game!
+A digital print of the lore page for your ghost
+Original soundtrack by John Matz as digital download
Your body is no more, but your spirit lives on! Your ghost will appear near the graveyard as an enemy (with your name) which players can encounter and fight

$70 - WRAITH
Includes all rewards from the tiers below plus:
+Upgrade your in-game ghost to a Wraith
+A digital print of the lore page for your Wraith
+An exclusive KS BackPack skin for your characters
Be directly responsible for even more carnage and suffering by being able to attach your name to a powerful Wraith that roams the areas surrounding the graveyard and places deep underground.

$80 - LET'S GET PHYSICAL! (EARLY BIRD) Limited reward (25 left of 25)
+Get the rewards of the Let's Get Physical Tier at a discounted rate!

$95 - LET'S GET PHYSICAL!
Includes all rewards from the tiers below plus:
+Physical "Illustrated Adventuring Guide"
+For The King or IronOak T-Shirt (Your choice)
-Shipping included for anywhere in US or Canada
-Please add $20 for shipping to other countries

$125 - DESIGNER - BLACKSMITH Limited reward (30 left of 30)
Includes all rewards from the tiers below plus:
+Design an in game item, weapon, or armor piece.
+Receive a one of a kind physical print of your item in a lore page style
+Designer Credit
-Shipping included for anywhere in US or Canada
-Please add $20 for shipping to other countries
Work with the design team to create an actual item that will appear in the game. Choose between a weapon, helmet, herb, or other trinket. Describe it's appearance and positive/negative effects!

$175 - DESIGNER - REAPER Limited reward (25 left of 25)
Includes all rewards from the non-designer tiers below plus:
+Become a dead adventurer whose body can be found in game.
+Receive a one of a kind digital print of your dead body in a lore page style.
+Designer credit
-Shipping included for anywhere in US or Canada
-Please add $20 for shipping to other countries
Your quest has come to an untimely end but you can still serve the king. Choose how you died, your appearance and name, and what you may have been carrying for other more fortunate adventurers to find.

$250 - FOR THE KING! - NO PHYSICAL
Includes all rewards from one of the designer tiers below plus:
+Includes 2 additional digital copies of For The King (3 total)
+Receive any future For The King DLC, Expansions, or Add-Ons for free
+Choose to design an in game item or dead adventurer (see designer tiers for more details, no physical print)
+Special Executive Producer Credit
Great for international supporters, no shipping costs. Bring along your friends with a total of 3 copies for the ultimate cooperative adventure with free DLC forever on all 3 games. Plus you get to choose to design an in game item or dead adventurer (see designer tiers for more details).

$300 - FOR THE KING!
Includes all rewards from one of the designer tiers below plus:
+Includes 2 additional digital copies of For The King (3 total)
+Receive any future For The King DLC, Expansions, or Add-Ons for free
+Choose to design an in game item or dead adventurer (see designer tiers for more details)
+Special Executive Producer Credit
-Shipping included for anywhere in US or Canada
-Please add $20 for shipping to other countries
Bring along your friends with a total of 3 copies for the ultimate cooperative adventure with free DLC forever on all 3 games. Plus you get to choose to design an in game item or dead adventurer (see designer tiers for more details)

$500 - CREATOR - SCOURGE Limited reward (5 left of 5)
Includes all rewards from the non-designer tiers plus:
+Become a scourge in game!
+Receive a one of a kind physical lore page about the scourge you created!
+Special Executive Producer and Creator Credit
-Shipping included for anywhere in US or Canada
-Please add $20 for shipping to other countries
If you can't beat 'em, join 'em! Work with our design team to create, design, and name a scourge, give them some wicked game altering abilities and be immortalized in game as the one everyone loathes!

$1000 - CREATOR - HERO Limited reward (5 left of 5)
Includes all rewards from the non-designer tiers plus:
+Become a playable character in game!
+Receive a one of a kind physical lore page about the character you created
+Special Executive Producer and Creator Credit
-Shipping included for anywhere in US or Canada
-Please add $20 for shipping to other countries
The ultimate hero. Work with our design team to create a character's traits, appearance, class, starting items and special abilities. Immortalize yourself or just be creative. Your character will appear in game as an adventurer that everyone can play.

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1. Well, maybe a little bit of shame. But what's the point of having a blog if you can't use it to help keep your son from living in our basement?

For The King: Get ready for Kickstarter

Colby Young, Gordon Moran, David Lam, and Sean Hoyle of IronOak Games are making a game called For The King.

Follow them on Facebook at IronOak Games or on Twitter at IronOakGames.

For The King is a turn based RPG that can be played solo or cooperatively online. Featuring long term strategic adventuring, turn based combat, and persistent choices, For The King aims to distill the epicness of traditional RPGs into an adventure that can be completed from beginning to end in a single session. Players must survive cunning enemies and creatures, wicked weather and brutal traps in their quest to solve the mysterious death of the king and bring order to the land.

• Online Multi-Player Adventure: Embark on your own or with up to 3 people online. Travel and fight together or dare to set off on your own.
• Short, Epic, Replayable: All the grandness of an epic adventure distilled into a 2 hour highly replayable game from start to finish.
• Turn Based Combat: Turn based combat with unique slot and combo system, battle stances, focus points, items, and special abilities.
• Strategic Procedural World: The map, realms, and locations you'll encounter will be different every play through. Every time it's a unique adventure.
• Persistent Lore: Collect and research in lore to build a unique game world by unlocking special persistent game mechanics in the order of your choosing.
• Day/Night Cycle: New challenges and horrors emerge at different times of day.
• Persistent Weapon Crafting: Craft powerful weapons over multiple play throughs.
• Dynamic Weather and Nature: Encounter weather and natural events that have a variety of effects, good and bad.

Gordon Moran¹ is the artist responsible for most of the images you see in the trailer below. He did not inherit his talent from me.

This is a game for those of us who loved Hack and Rogue and don't like the modern games.

If you like the idea, get ready for the Kickstarter campaign that begins tomorrow. As soon as it starts, I'll post the link and the list of rewards. I'll also tell you what characters Ms. Sandwalk and I are buying. You will get to see them when you play the game.

If you give enough money you may be able to name an evil character. Wouldn't it be fun to battle "Casey Luskin" or Jonathan Wells"?

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1. He is my son. I have a personal interest in promoting this game. I don't want him moving into the basement. Just so you know.

Best blog post in the past year

3 Quarks Daily is running their annual contest to pick the best blog posts in the past year. The finalists will be picked by popular vote and the winner will be selected from the finalists by Nick Lane. You can review the rules at: Nick Lane to Judge 6th Annual 3QD Science Prize.

The formal description of the prize is "6th annual prize for the best blog and online-only writing in the category of science." This is important because although the rules refer to "blog posts" and "blog entries" it's clear that most of the nominees are more like online poplar science articles than typical blog posts.

Here's a list of the current nominees ...