De novo genes in the news

I recently posted — and made a video about — a story about how de novo genes are made. I guess I was more timely than I expected, because The Scientist just posted on article on the same topic. It’s specifically about the work of Li Zhao, who is interested in the birth of new genes with novel functions, and is building on some other work done at UC Davis.

But around the same time Zhao began her research, new evidence challenged this longstanding view [that new genes don’t appear very often] with an alternative path. Population geneticist David Begun at the University of California, Davis (UC Davis) identified several de novo genes—genes originating from scratch, or non-coding DNA—in Drosophila melanogaster, the common fruit fly. Of the five genes, four occurred on the X chromosome and predominantly expressed in the testes, possibly under sexual selection pressures.

One other thing I should mention: my previous article focused on de novo genes in humans, who are terrible experimental subjects. Li Zhao is working on Drosophila, and there’s a reason flies are a premier model system for this kind of work — you can get multiple generations fast, you can do all kinds of genetic manipulations on them, and you can compare different lineages to evaluate the effects of the presence or absence of a specific gene. Or hundreds of genes, as she is finding.

By characterizing the transcriptomes of six previously sequenced D. melanogaster strains in the testes, Zhao and her colleagues uncovered potential de novo candidates. Of these, they identified 142 polymorphic (which segregated and evolved under selection) and 106 fixed (which remained consistent since the split from a common ancestor) de novo genes. Most of these candidates were regulated by cis elements, with expression driven by regulatory sequences just upstream of the new transcripts. The vast majority contained open reading frames (ORFs)—sections that could potentially produce proteins, marked by start and stop codons—of at least 150 base pairs. When comparing these sequences to ancestral genomes and non-expressing Drosophila strains, the same ORFs appeared, suggesting that the gene expression was driven primarily by regulatory changes.

Zhao and her colleagues proposed that these de novo genes may have undergone natural selection, as highly expressed genes were generally longer and more complex than those expressed at lower levels. However, whether these sequences were translated into proteins or served other functions remained unclear at the time. “Biology is more complex than what we imagine,” said Zhao.

Cool. But I’m going to don my skeptical hat, and suggest that I’m not seeing evidence that these novel genes are significant. The mechanisms for generating them are so easy that we shouldn’t be surprised that new genes are bubbling up out of the mostly chaotic junk in the genome, but when you don’t know what role those genes are playing in the organism, it’s a reach to suggest that they are important. I’m also unconvinced by observations of tissue-specific regulation during development — it’s also not difficult for regulatory sequences to be attached to a gene. Is it significant that so many of these novel genes are expressed in the testes? Male patters of gene expression in the gonads is a special case, and spurious expression could persist there because it has specific effects on sperm maturation that aren’t reflected in adult survival.

It’s still interesting stuff. I like the idea that entirely new genes trickle into populations and could contribute to variation in surprising ways.

Proving that free speech was never the goal

I guess we aren’t done with Charlie Kirk. The talk show host, Jimmy Kimmel, made a few entirely accurate remarks that were mainly critical of Trump and the Right’s efforts to capitalize on an assassination, and on Trump’s infantile mental ability.

On Tuesday’s “Jimmy Kimmel Live!” the host, during his monologue, addressed Charlie Kirk’s murder and the way some Republicans were seeking to portray the suspect, Tyler Robinson. “We hit some new lows over the weekend with the MAGA gang desperately trying to characterize this kid who murdered Charlie Kirk as anything other than one of them and doing everything they can to score political points from it,” Kimmel said, before pivoting to a segment where a reporter asked Trump how he was holding up, and he responded, in part, by bragging about White House construction.

“This is not how an adult grieves the murder of someone he called a friend,” Kimmel said. “This is how a 4-year-old mourns a goldfish.”

Kimmel also talked about Trump’s appearance on “Fox & Friends,” where Trump related the story about how he learned of Kirk’s death, and talked again about the construction.

“There’s something wrong with him,” Kimmel said. “There really is. Who thinks like that?”

For that, he has been yanked off the air indefinitely, maybe permanently. This is political censorship; his words were not particularly offensive to anyone, especially at a time when Trump is clearly losing his faculties, and when right-wing figures are declaring war on the Left.

So much for free speech. We knew that was never their honest goal.

Kirk was a parasite, notable for the fact that he used the illusion of civility to worm his way into the affections of pundits on both sides of the aisle, who praised the way he said things, rather than the content of his speech. He was an unabashed racist, anti-semite, misogynist, Christian nationalist, and queer-baiter, but we’re not allowed to say that now — in fact, quoting his own despicable words is a great way to get canceled.

They’re probably sharpening their knives for Ta-Nehisi Coates, who still speaks truth to power.

Before he was killed last week, Charlie Kirk left a helpful compendium of words—ones that would greatly aid those who sought to understand his legacy and import. It is somewhat difficult to match these words with the manner in which Kirk is presently being memorialized in mainstream discourse. New York Times columnist Ezra Klein dubbed Kirk “one of the era’s most effective practitioners of persuasion” and a man who “was practicing politics in exactly the right way.” California governor Gavin Newsom hailed Kirk’s “passion and commitment to debate,” advising us to continue Kirk’s work by engaging “with each other, across ideology, through spirited discourse.” Atlantic writer Sally Jenkins saluted Kirk, claiming he “argued with civility” and asserting that his death was “a significant loss for those who believe engagement can help bridge disagreements.”

The mentions of “debate” and “engagement” are references to Kirk’s campus tours, during which he visited various colleges to take on whoever come may. That this aspect of Kirk’s work would be so attractive to writers and politicians is understandable. There is, after all, a pervasive worry, among the political class, that college students, ensconced in their own bubbles, could use a bit of shock therapy from a man unconcerned with preferred pronouns, trigger warnings, and the humanity of Palestinians. But it also shows how the political class’s obsession with universities blinds it to everything else. And the everything-else of Kirk’s politics amounted to little more than a loathing of those whose mere existence provoked his ire.

It is not just, for instance, that Kirk held disagreeable views—that he was pro-life, that he believed in public executions, or that he rejected the separation of church and state. It’s that Kirk reveled in open bigotry. Indeed, claims of Kirk’s “civility” are tough to square with his penchant for demeaning members of the LGBTQ+ community as “freaks” and referring to trans people with the slur “tranny.” Faced with the prospect of a Kamala Harris presidency, Kirk told his audience that the threat had to be averted because Harris wanted to “kidnap your child via the trans agenda.” Garden-variety transphobia is sadly unremarkable. But Kirk was a master of folding seemingly discordant bigotries into each other, as when he defined “the American way of life” as marriage, home ownership, and child-rearing free of “the lesbian, gay, transgender garbage in their school,” adding that he did not want kids to “have to hear the Muslim call to prayer five times a day.” The American way of life was “Christendom,” Kirk claimed, and Islam—“the sword the left is using to slit the throat of America”—was antithetical to that. Large “dedicated” Islamic areas were “a threat to America,” Kirk asserted, and New York mayoral candidate Zohran Mamdani was a “Mohammedan,” with Kirk supposing that anyone trying to see “Mohammedism take over the West” would love to have New York—a “prior Anglo center”—“under Mohammedan rule.”

Kirk habitually railed against “Black crime,” claiming that “prowling Blacks go around for fun to go target white people.” He repeated the rape accusations against Yusef Salaam, a member of the exonerated Central Park Five who is now a New York City councilman, calling him a “disgusting pig” who had gotten away with “gang rape.” Whatever distaste Kirk held for Blacks was multiplied when he turned to those from Haiti. Haiti was, by Kirk’s lights, a country “infested with demonic voodoo,” whose migrants were “raping your women and hunting you down at night.” These Haitians, as well as undocumented immigrants from other countries, were “having a field day,” per Kirk, and “coming for your daughter next.” The only hope was Donald Trump, who had to prevail, lest Haitians “become your masters.”

The point of this so-called mastery was as familiar as it was conspiratorial—“great replacement.” There was an “anti-white agenda,” Kirk howled. One that sought to “make the country more like the Third World.” The southern border was “the dumping ground of the planet,” he claimed, and a magnet for “the rapists, the thugs, the murderers, fighting-age males.” “They’re coming from across the world, from China, from Russia, from Middle Eastern countries,” he said, “and they’re coming in and they’re coming in and they’re coming in and they’re coming in…”

You can probably imagine where this line of thinking eventually went.

“Jewish donors,” Kirk claimed, were “the number one funding mechanism of radical open-border, neoliberal, quasi-Marxist policies, cultural institutions, and nonprofits.” Indeed, “the philosophical foundation of anti-whiteness has been largely financed by Jewish donors in the country.”

Tommy Robinson, a far-right British activist, held a rally this week in which supporters chanted support for Kirk. The gathering turned violent, injuring 26 police officers.Lab Ky Mo/SOPA Images/LightRocket/Getty Images.

Kirk’s bigotry was not personal, but extended to the institution he founded, Turning Point USA. Crystal Clanton, the group’s former national field director, once texted a fellow Turning Point employee, “I HATE BLACK PEOPLE. Like fuck them all … I hate blacks. End of story.” One of the group’s advisers, Rip McIntosh, once published a newsletter featuring an essay from a pseudonymous writer that said Blacks had “become socially incompatible with other races” and that Black culture was an “un-fixable and crime-ridden mess.” In 2022, after three Black football players were killed at another college, Meg Miller, president of Turning Point’s chapter at the University of Missouri, joked (“joked”) in a social media message, “If they would have killed 4 more n-ggers we would have had the whole week off.”

Kirk subscribed to some of the most disreputable and harmful beliefs that this country has ever known. But it is still chilling to think that those beliefs would be silenced by a gunshot. The tragedy is personal—Kirk was robbed of his life, and his children and family will forever live with the knowledge that a visual record of that robbery is just an internet search away. And the tragedy is national. Political violence ends conversation and invites war; its rejection is paramount to a functioning democracy and a free society. “Political violence is a virus,” Klein noted. This assertion is true. It is also at odds with Kirk’s own words. It’s not that Kirk merely, as Klein put it, “defended the Second Amendment”—it’s that Kirk endorsed hurting people to advance his preferred policy outcomes.

In 2022, when Kirk was frustrated, for instance, by the presence of Lia Thomas on the University of Pennsylvania women’s swim team, Kirk did not call for “spirited discourse.” Instead, while discussing a recent championship tournament, he said he would have liked to have seen a group of fathers descend from the stands, forming “a line in front of [Lia] Thomas and saying, ‘Hey, tough guy, you want to get in the pool? ’Cause you’re gonna have to come through us.” Mere weeks before his death, Kirk reveled in Trump’s deployment of federal troops to DC. “Shock and awe. Force,” he wrote. “We’re taking our country back from these cockroaches.” And in 2023, Kirk told his audience that then president Joe Biden was a “corrupt tyrant” who should be “put in prison and/or given the death penalty for his crimes against America.”

What are we to make of a man who called for the execution of the American president, and then was executed himself? What are we to make of an NFL that, on one hand, encourages us to “End Racism,” and, on the other, urges us to commemorate an unreconstructed white supremacist? And what of the writers, the thinkers, and the pundits who cannot separate the great crime of Kirk’s death from the malignancy of his public life? Can they truly be so ignorant to the words of a man they have so rushed to memorialize? I don’t know. But the most telling detail in Klein’s column was that, for all his praise, there was not a single word in the piece from Kirk himself.

More than a century and a half ago, this country ignored the explicit words of men who sought to raise an empire of slavery. It subsequently transformed those men into gallant knights who sought only to preserve their beloved Camelot. There was a fatigue, in certain quarters, with Reconstruction—which is to say, multiracial democracy—and a desire for reunion, to make America great again. Thus, in the late 19th century and much of the 20th, this country’s most storied intellectuals transfigured hate-mongers into heroes and ignored their words—just as, right now, some are ignoring Kirk’s.

Words are not violence, nor are they powerless. Burying the truth of the Confederacy, rewriting its aims and ideas, and ignoring its animating words allowed for the terrorization of the Black population, the imposition of apartheid, and the destruction of democracy. The rewriting and the ignoring were done not just by Confederates, but also by putative allies for whom the reduction of Black people to serfdom was the unfortunate price of white unity. The import of this history has never been clearer than in this moment when the hard question must be asked: If you would look away from the words of Charlie Kirk, from what else would you look away?

Fuck Ezra Klein, fuck Gavin Newsom, and fuck ABC news. Also, damn these people who are going to speak at his memorial service, you know they aren’t going to bring up his unapologetic racism, except to praise it. Especially Stephen Miller.

Charlie Kirk’s widow, Erika Kirk
President Trump
Vice President JD Vance
White House Chief of Staff Susie Wiles
Secretary of State Marco Rubio
Health and Human Services Secretary Robert F. Kennedy Jr.
Secretary of Defense Pete Hegseth
Director of National Intelligence Tulsi Gabbard
Donald Trump Jr.
Tucker Carlson
Deputy Chief of Staff for Policy Stephen Miller
Ambassador to India nominee Sergio Gor

I can understand the widow speaking, but the rest are all there to promote hatred. Don’t expect an honest word out of any of them.

Must-see TV!

He always looks like such a buffoon, even with a stupid crown

Donald Trump is visiting England, why I don’t know. I hope all my friends in Great Britain are prepared to boo and hiss and shout rude things at him while he’s there. It seems some in the media are prepared to respond appropriately to him.

More than 100 of Donald Trump’s inaccurate statements are to be dissected by Channel 4 to coincide with his state visit, in what it described as “the longest uninterrupted reel of untruths, falsehoods and distortions ever broadcast on television”.

Give him hell. That’s what our media should be doing but isn’t.

Maybe we’ll get it on YouTube or something later?

Looking forward to going under the knife

I have arthroscopic surgery scheduled for the 26th of September. Hooray! I first went to this doctor in July, and he had hopes that I’d heal up with time — I guess that I was hobbling in on a cane and grimacing with every step told him that he’s going to have to poke holes in me and stitch something up.

Then he thinks I’ll need about two weeks of recovery time, unless they discover something horrible. I’ll try to be optimistic, but optimism isn’t working out so far.

When we got home from the clinic, there was another chrysalis just outside my door. Maybe that’s a promising sign?

It’s going to be hard going back to work in January

I’m relieved to not have any teaching obligations this term. I’ve been doing weekly homework problems/quizzes using the university standard Canvas tool, and I’ve always been pretty liberal with that: if students want to work together on the problems, that’s all to the good. Communicating and helping each other is useful for learning.

But I’m getting all these emails now about a feature that was added. AI. There’s a box on the screen to invoke Google Lens and Homework Helper, so I could be putting all the effort into composing a problem set, and the students could solve it by pushing a button. The university has been putting in something called Honorlock to disable AI access in problem sets, which seems to working inconsistently.

I’m not alone in resenting all these shortcuts that are being placed in our teaching.

It’s a sentiment that pervades listservs, Reddit forums and other places where classroom professionals vent their frustrations. “I’m not some sort of sorcerer, I cannot magically force my students to put the effort in,” complains one Reddit user in the r/professor subreddit. “Not when the crack-cocaine of LLMs is just right next to them on the table.” And for the most part, professors are on their own; most institutions have not established blanket policies about AI use, which means that teachers create and enforce their own. Becca Andrews, a writer who teaches journalism at Western Kentucky State University, had “a wake-up call” when she had to fail a student who used an LLM to write a significant amount of a final project. She’s since reworked classes to include more in-person writing and workshopping, and notes that her students — most of whom have jobs — seem grateful to have that time to complete assignments. Andrews also talks to her students about AI’s drawbacks, like its documented impact on critical-thinking faculties: “I tell them that their brains are still cooking, so it’s doubly important to think of their minds as a muscle and work on developing it.”

Last spring’s bleakest read on the landscape was New York Magazine’s article, “Everyone Is Cheating Their Way Through College,” which included a number of deeply unsettling revelations from reporter James D. Walsh — not just about how widespread AI dependence has already become, but about the speed with which it is changing what education means on an empirical level. (One example Walsh cites: a professor who “caught students in her Ethics and Technology class using AI to respond to the prompt ‘Briefly introduce yourself and say what you’re hoping to get out of this class.’”) The piece is bookended with the story of a Columbia student who invented a tool that allowed engineers to cheat on coding interviews, who recorded himself using the tool in interviews with companies, and was subsequently put on academic leave. During that time, he invented another app that makes it easy to cheat on everything. He raised $5.3 million in venture capital.

I’m left wondering, who is asking for these widgets to be installed in our classes? Are there salespeople for software like Canvas who enthusiastically sell these features for cheating to university administrators who think more AI slop benefits learning? Why, if I’m trying to teach genetics, do I have to wrestle around garbage shortcuts imposed on me by the university that short circuit learning?

Several years ago, I was happy to embrace these new tools, and found it freeing to be doings exams and homework online — it meant 4 lecture hours in the semester that weren’t dedicated to proctoring students hunched over exams. No more. When I get back into a class in the Spring, I’m going to be resurrecting blue books.

Oh, and since I was wondering who kept shoveling this counterproductive crap into my classes, I’ve got one answer.

It’s not coincidental that the biggest booster of LLMs as a blanket good is a man who, like many a Silicon Valley wunderkind who preceded him, dropped out of college, invented an app and hopped aboard the venture-capital train. As a leading booster of AI, Sam Altman has been particularly vocal in encouraging students to adopt AI tools and prioritize “the meta ability to learn” over sustained study of any one subject. If that sounds like a line of bull, that’s because it is. And it’s galling that the opinion of someone who dropped out of college — because why would you keep learning when there’s money to be made and businesses to found? — is constantly sought out for comment on what tools students should and shouldn’t be using. Altman has brushed off educators’ concerns about the drawbacks of AI use in academia and has even suggested that the definition of cheating needs to evolve.

Still falling apart

My lower limbs have been making this sabbatical half-year hellish. First, there was an unexpected meniscus tear in my right knee; that pain is still there, a sharp needle in that one joint. Then my left knee started swelling up and protesting every time I bent it; that knee has been a weak point for a half century, and I think being more reliant on that leg made it protest more. Then I had a gout flare-up in the left foot, and those of you who’ve suffered one of those know how agonizing it can be. And now, this morning, I wake up to my right ankle experiencing a sharp grinding pain, like it’s going on strike in sympathy with the other joints. Basically everything below the hips hurts right now. I’m also going stir crazy, trapped in my office.

Two things are helping me keep my perspective.

First, years ago I was funded by a cancer training grant, which required me to attend weekly classes on cancer. Many of these were great and useful to me, when they were taught by molecular biologists, but every once in a while they’d bring in a cancer surgeon, which was a very different experience. Most memorable was the guy who had a patient with bone cancer in his lower limbs that spread up into his pelvis. To keep him alive, and to generate the most horrific series of slides I’ve ever seen, they cut him in half at the waist, threw out his legs and pelvis, and tied him off with a knot, where the tag end of his colon and a couple of ureters were left dangling, dripping into a plastic bag.

The happy part of the story is that he lived long enough afterwards to escort his daughter down the aisle at her wedding, which is all he wanted. Also, I’m left with some terrible images that tell me it could always be worse.

They still look a little creepy to me

Second, I’ve always been kind of an anti-foot-fetishist. I’m a hand man. Feet have always seemed like ugly, malformed hands, so I’m most comfortable keeping them tucked away in a pair of shoes. My recent problems mean I’ve been shoeless most of the summer, and when I am getting up to shuffle around, my attention is often focused on my feet. I have started to seriously appreciate my toes. Really, they’ve evolved to spread out the load at the ends of my feet, and I see them doing an important job that has always been obscured by footwear. Then I notice that they also conform to the substrate — we didn’t evolve to walk on flat floors, but on more rugged ground, and there they spread out so that all five toes are in contact. Sometimes, when I’m trying to get from the bedroom to the bathroom, I look down and have to admire the job my toes are doing.

So I’m getting by. I have an appointment with my orthopedist tomorrow, and hope he can fix one or two of my problems.

Health advice — consider the source

You want to know where all these “health” cranks will take you?

If you have a rash…pee on it…
If you have a cut or scar….pee on it.
Want clearer skin….pee on it
Want to feel better….drink your pee
Fasting….drink your pee….
Eye problems?…..take a glass dropper snd pee in it. Every night before bed drip it in your eyes. And in the morning when you wake! Watch your eye strain vanish! Wanna go a step further? How about programming it! Write on a label “Heal eyes/Clear vision”
Notice how in desperate situations when we are stuck in a desert or on a boat we drink our urine and it keeps us alive!! If it was some toxic poison it would kill us! Instead it gives life to go on!! Wake up…. Your urine is the most potent remedy to all your issues and you ignore it. Drink it.

Please don’t do any of that…except that I guess it’s OK to write whatever you want on a label. It just won’t do anything.

If you’re stranded on a desert island, drinking urine won’t keep you alive — it will make your situation worse.

The most common reason for drinking urine in movies and pop media is to stave off dehydration. If someone is lost at sea or deep in the desert, they are sometimes depicted as drinking their own urine to preserve moisture. This is highly unlikely to actually help.

The average adult’s urine contains a significant amount of salt, which gets much more concentrated if you become dehydrated. Dehydrated individuals can quickly reach excessive levels of sodium in their urine.

Consuming more sodium is linked to increasing your thirst. Higher levels of sodium in your body quickly lead to feeling thirstier. By drinking urine, which contains a high concentration of sodium, you can quickly develop a negative feedback loop in which you feel thirstier despite drinking liquids.

Sweating can increase the risks associated with drinking urine. Typically, sweating releases water and salts from your body. When you’re also losing salt in your urine, your electrolyte levels stay balanced. However, when you’re re-consuming the salts from your urine, you are concentrating salts inside your body and making your thirst worse. The field manual for the US Army explicitly recommends avoiding drinking urine as a form of hydration, even in emergency situations.

I think the US Army Field Manual is evidence-based, unlike anything Damien Michaels Extreme says. I predict that Damien Michaels Extreme stinks.

Never has a man’s own words so adeptly justified contempt for him

People are having a grand time digging through Charlie Kirk’s own words to show that he deserved being dragged.

He was killed on camera. No one’s family deserves to have to witness that. It’s unthinkably cruel that people would then go on the internet and use their platform to say about an innocent man that “l don’t care that he’s dead.” “He’s not a hero.” “He’s a scumbag.” “He shouldn’t be celebrated.”
I’m talking about George Floyd. You thought | was talking about Charlie Kirk? No, those are actual quotes BY Charlie Kirk about George Floyd. Outrageous that anyone would say that of the dead, right?

It’s tempting to sit down and just compile a list of all the hateful things the man said — I could spend the next few weeks documenting what a horrible little man he was. But that’s something that should have been done before he was killed, because what should have been assassinated was his reputation while he was cuddling up to racists and anti-semites and anti-gay and trans people, all that stuff journalists shied away from while he was living and building a movement. All we can do now is condemn him when it is too late.

When asked about mass shootings he said, “I think it’s worth it. I think it’s worth it to have a cost of, unfortunately, some gun deaths every single year, so that we can have the Second Amendment.” Perhaps Kirk did not believe that his own life would be cut short by gun violence, but, like the rest of us, he has witnessed countless school shootings. When he said “some gun deaths” are acceptable, he surely knew he lived in a country where the deaths he deemed acceptable included those of children, some of whom were the age of his own. There is no inherent virtue in caring about your own children; that is the bare minimum requirement for effective parenting. Virtue lies in caring about the safety and well-being of children you don’t know.

On that front, I’m fairly sure Kirk did not care about my child. My child lives in Brooklyn, in a progressive family. His mother works and does not have a marriage where she is considered inferior to her husband or required to obey him, as Kirk arrogantly told Taylor Swift she should do after learning of her engagement. (“Reject feminism,” he said. “You’re not in charge.”) We also live in a Haitian immigrant neighborhood, and if you only listened to Charlie Kirk, you might be under the impression that my neighbors eat pets. You would also be encouraged to believe that, simply by virtue of being non-white immigrants, they were “replacing” white people—and that, since they are also Black, they are dangerous. “Happening all the time in urban America,” he said, “prowling Blacks go around for fun to go target white people, that’s a fact.”

Now is the time to talk about the evil being done by Trump and Steven Miller and JD Vance and Pete Hegseth and RFK jr (I’m beginning to see some open detestation of that foul creature) and all the billionaires backing the current political moment. I’m done with Kirk. He’s dead, good.

A great response from a Christian minister:

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