I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! I thought I'd post the TOC for each chapter as I finish the first drafts. Here's chapter 2.
Chapter 2: The Big Picture
- How much of the genome has been sequenced?
- Whose genome was sequenced?
- How many genes?
- Pseudogenes
- Regulatory sequences
- Origins of replication
- Centromeres
- Telomeres
- Scaffold Attachment regions (SARs)
- Transposons
- Viruses
- Mitochondrial DNA (NumtS)
- How much of our genome is functional?
I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! I thought I'd post the TOC for each chapter as I finish the first drafts. Here's chapter 1.
Chapter 1: Introducing Genomes
- The genome war
- What is DNA?
- Chromatin
- How big is your genome?
- Active genes?
- What do you need to know?
Michio Kaku is a theoretical physicist at the City College of New York. Like many physicists, he thinks he's smart enough to know everything about everything so he doesn't hesitate to lecture people about evolution.
In this case. He's telling us that humans have reached perfection in all adaptive traits so there can't be any more selection for things like bigger brains. He tells us that human evolution has stopped because no animals are chasing us in the forest any more. He also let's us know that there are no more isolated populations because of jet planes. Watch the video to see how little he understands.
There are two competing worldviews in the fields of biochemistry and molecular biology. The distinction was captured a few years ago by Laurence Hurst commenting on pervasive transcription when he said, "So there are two models; one, the world is messy and we're forever making transcripts we don't want. Or two, the genome is like the most exquisitely designed Swiss watch and we don't understand its working. We don't know the answer—which is what makes genomics so interesting." (Hopkins, 2009).
There's an interesting video of ten famous women scientists at Interesting S_Word: [Top 10 Female Scientists of History]. The image of Rosalind Franklin caught my eye (see right).
If you want to be a serious participant in the debate over junk DNA then you should watch this video. Dan Graur presents the standard arguments for junk DNA—most of which have been around for decades. He also destroys the main arguments against junk DNA. You are entitled to choose sides in this debate but you are not entitled to pose as an authority unless you know the best arguments from BOTH sides. It is not sufficient to just quote evidence for function as support for your bias. You must also refute the evidence for junk. You have to show why it is wrong or misleading.
Hat Tip: PZ Myers
A reader directed me to a 2015 ENCODE workshop with online videos of all the presentations [From Genome Function to Biomedical Insight: ENCODE and Beyond]. The workshop was sponsored by the National Human Genome Research Institute in Bethesda, Md (USA). The purpose of the workshop was ...
Today is Darwin Day but I'm too busy with other things to write a new post in his honor. So here's a post from 2007 (slightly updated) to help you enjoy the day.
Gwen Raverat was Darwin's granddaughter (daughter of George Darwin). She described Down House as she knew it in the years shortly after Darwin died.Of all places at Down, the Sandwalk seemed most to belong to my grandfather. It was a path running round a little wood which he had planted himself; and it always seemed to be a very long way from the house. You went right to the furthest end of the kitchen garden, and then through a wooden door in the high hedge, which quite cut you off from human society. Here a fenced path ran along between two great lonely meadows, till you came to the wood. The path ran straight down the outside of the wood--the Light Side--till it came to a summer-house at the far end; it was very lonely there; to this day you cannot see a single building anywhere, only woods and valleys.I became interested in Darwin's children about fifteen years ago when I first began to appreciate the influence they had on his life. We all know the story of Annie's death when she was ten years old and how this led to Darwin's rejection of religion. There were other tragedies but Charles and Emma turned out to be very good parents.
Here's a short biography of each of Darwin's children from AboutDarwin.comWilliam Erasmus Darwin
The first of Darwin's children was born on December 27, 1839. He was a graduate of Christ’s College at Cambridge University, and was a banker in Southampton. He married Sara Ashburner from New York, but they had no children. William died in 1914.
Anne Elizabeth Darwin
Born on March 2 1841, and died at the age of ten of tuberculosis on April 22, 1851. It was the death of Annie that radically altered Darwin’s belief in Christianity.
Mary Eleanor Darwin
Born on September 23, 1842 but died a few weeks later on October 16th.
Henrietta Emma Darwin ("Etty")
Born on September 25, 1843 and married Richard Buckley Litchfield in August of 1871. She lived 86 years and edited Emma's (her mother) personal letters and had them published in 1904. She had no children.
George Howard Darwin
Born on July 9, 1845. He was an astronomer and mathematician, and became a Fellow of the Royal Society ... in 1879. In 1883 he became the Plumian Professor of Astronomy and Experimental Philosophy at Cambridge University, and was a Barrister-at-Law. He studied the evolution and origins of the solar system. George married Martha (Maud) du Puy from Philadelphia. They had two sons, and two daughters. He died in 1912.
Elizabeth Darwin
Born on July 8, 1847 and died in 1926. She never married and had no children.
Francis Darwin
Born on August 16, 1848. He became a botanist specializing in plant physiology. He helped his father with his experiments on plants and was of great influence in Darwin's writing of "The Power of Movement in Plants" (1880). He was made a Fellow of the Royal Society in 1879, and taught at Cambridge University from 1884, as a Professor of Botany, until 1904. He edited many of Darwin's correspondence and published "Life and Letters of Charles Darwin" in 1887, and "More Letters of Charles Darwin" in 1903. He also edited and published Darwin’s Autobiography. He married Amy Ruck but she died when their first child, Bernard, was born in September of 1876. He then married Ellen Crofts in September of 1883, and they had one daughter, Frances in 1886. Francis was knighted in 1913, and died in 1925.
Leonard Darwin
Born on January 15, 1850. He became a soldier in the Royal Engineers in 1871, and was a Major from 1890 onwards. He taught at the School of Military Engineering at Chatham from 1877 to 1882, and served in the Ministry of War, Intelligence Division, from 1885-90. He later became a liberal-unionist MP for the town of Lichfield in Staffordshire 1892-95, and was president of the Royal Geological Society 1908-11. Leonard married Elizabeth Fraser in July of 1882. He married a second time, but had no children and died in 1943.
Horace Darwin
Born on May 13, 1851. He was a graduate of Trinity College, Cambridge, and became an engineer and a builder of scientific instruments. In 1885 he founded the Cambridge Scientific Instrument Company. He was the Mayor of Cambridge from 1896-97, and was made a Fellow of the Royal Society in 1903. Horace married Emma Farrer in January of 1880 and they had three children. He died in 1928.
Charles Waring Darwin
Born on December 6, 1856 but died on June 28 1858.
ENCODE researchers answered a bunch of question on Reddit a few days ago. I asked them to give their opinion on how much junk DNA is in our genome but they declined to answer that question. However, I think we can get some idea about the current thinking in the leading labs by looking at the questions they did choose to answer. I don't think the picture is very encouraging. It's been almost five years since the ENCODE publicity disaster of September 2012. You'd think the researchers might have learned a thing or two about junk DNA since that fiasco.
The question and answer session on Reddit was prompted by award of a new grant to ENCODE. They just received 31.5 million dollars to continue their search for functional regions in the human genome. You might have guessed that Dan Graur would have a few words to say about giving ENCODE even more money [Proof that 100% of the Human Genome is Functional & that It Was Created by a Very Intelligent Designer @ENCODE_NIH].
Check out Science AMA Series: We’re Drs. Michael Keefer and James Kobie, infectious .... (Thanks to Paul Nelson for alerting me to the discussion.)
Here's part of the introduction ...Yesterday NIH announced its latest round of ENCODE funding, which includes support for five new collaborative centers focused on using cutting edge techniques to characterize the candidate functional elements in healthy and diseased human cells. For example, when and where does an element function, and what exactly does it do.
UCSF is host to two of these five new centers, where researchers are using CRISPR gene editing, embryonic stem cells, and other new tools that let us rapidly screen hundreds of thousands of genome sequences in many different cell types at a time to learn which sequences are biologically relevant — and in what contexts they matter.
Today’s AMA brings together the leaders of NIH’s ENCODE project and the leaders of UCSF’s partner research centers.
Your hosts today are:
Nadav Ahituv, UCSF professor in the department of bioengineering and therapeutic sciences. Interested in gene regulation and how its alteration leads to morphological differences between organisms and human disease. Loves science and juggling.
Elise Feingold: Lead Program Director, Functional Genomics Program, NHGRI. I’ve been part of the ENCODE Project Management team since its start in 2003. I came up with the project’s name, ENCODE!
Dan Gilchrist, Program Director, Computational Genomics and Data Science, NHGRI. I joined the ENCODE Project Management team in 2014. Interests include mechanisms of gene regulation, using informatics to address biological questions, surf fishing.
Mike Pazin, Program Director, Functional Genomics Program, NHGRI. I’ve been part of the ENCODE Project Management team since 2011. My background is in chromatin structure and gene regulation. I love science, learning about how things work, and playing music.
Yin Shen: Assistant Professor in Neurology and Institute for Human Genetics, UCSF. I am interested in how genetics and epigenetics contribute to human health and diseases, especial for the human brain and complex neurological diseases. If I am not doing science, I like experimenting in the kitchen.
I think philosophy has lost its way. The discipline gives credence to religious philosophers who write about god(s) and to other philosophers who reject determinism and think the mind-body problem is still an open question. Philosophers still debate the validity of the ontological argument. Philosophers of science have not even settled the question of what is science, let alone come up with a valid answer of how to do it. There are few other disciplines that are still respected after several hundred years of trying, and failing, to answer the most fundamental questions in their field. Many academic philosophy department are hotbeds of political correctness and just plain politics.
Watch Ricky Gervais explain atheism to Stephen Colbert. I like his explanation of the difference between science and religion. In fact, I like it so much I'm going to embellish it a bit and present it here ...
Imagine what would happen after a giant meteor strike that wipes out everyone except for a small native tribe in the Andes that had no contact with other people before the apocalypse. All books and all knowledge will be destroyed.
Otangelo Grasso is a creationist who's convinced he can learn to understand biochemistry by reading what's on the internet and copy-pasting it into his website. He then takes that limited knowledge and concludes that evolution is impossible. He often poses "gotcha" questions based on his flawed understanding.
His behavior isn't very different from most other creationists who suffer from Dunning-Kruger Disease but he happens to be someone who I thought could be educated.It's not Saturday morning but you can enjoy this cartoon anyway.
Photosynthesis is the series of reactions that capture light energy and use it to make ATP and sometimes reducing equivalents (e.g NADPH). There are many different versions of photosynthesis. One of the simplest is found in purple bacteria where the process results in formation of a proton gradient that's used to drive ATP synthesis.
I just realized that I don't have a post devoted to the evolution of the citric acid cycle. This need to be remedied since I often talk about it. It's a good example of how an apparently irreducibly complex pathway can arise by evolution. It's also a good example to get students to think outside of the box. Undergraduate biochemistry courses usually concentrate on human physiology and too often students transfer that bias to all other species. They assume that what happens in humans is what happens in plants, fungi, protozoa, and bacteria.1
Here's what the standard citric acid cycle looks like (Moran et al., 2011 p. 393).
This is so frustrating. I've been debating creationists for almost 30 years. My colleagues and I have tried time and time again over those three decades to educate them about real evolutionary theory. We've also tried to teach them about the difference between evolution and the history of life. In order to explain the history of life on Earth you need to account for mass extinctions and other chance events that have nothing to do with evolution. They refuse to listen.
The latest evidence is a recent post by David Klinghoffer [Theory of Evolution? Call It a "Narrative" Instead]. He says,The theory of evolution by natural selection operating on random mutations, as a sweeping explanation for life and how it got there, is a "narrative." It presents a very smooth story, persuasive to most scientists. The facts may all be true, but the conclusion: BS.
The human apolipoprotein E gene (ApoE) has several alleles segregating in the human population. One of them, E4, is associated with increased risk of Alzheimer's. Ed Yong, writing for The Atlantic, asks "Why Do Humans Still Have a Gene That Increases the Risk of Alzheimer's?
I can think of several answers off the top of my head. The most important one is that Alzheimer's has very little effect on your ability to have children. The disease may not even have developed in most of our ancestors who tended to die younger. In order to be subject to negative selection the allele has to affect adults before they reproduce.“It doesn’t make sense,” says Ben Trumble, from Arizona State University. “You’d have thought that natural selection would have weeded out ApoE4 a long time ago. The fact that we have it at all is a little bizarre.”
I'm working on a chapter about pervasive transcription and how it relates to the junk DNA debate. I found a short review in Nature from 2002 so I decided to see how much progress we've made in the past 15 years.
Most of our genome is transcribed at some time or another in some tissue. That's a fact we've known about since the late 1960s (King and Jukes, 1969). We didn't know it back then, but it turns out that a lot of that transcription is introns. In fact, the observation of abundant transcription led to the discovery of introns. We have about 20,000 protein-coding genes and the average gene is 37.2 kb in length. Thus, the total amount of the genome devoted to these genes is about 23%. That's the amount that's transcribed to produce primary transcripts and mRNA. There are about 5000 noncoding genes that contribute another 2% so genes occupy about 25% of our genome.
Ann Gauger was reading a cell paper the other day [Digging Deep in Biology: "Things Get Even More Complicated When You Look Closer"]. The subject was the localization of citric acid cycle enzymes and pyruvate dehydrogenase (PDH). She did a little digging and this is what astonished her ...
... so I looked up pyruvate dehydrogenase and found to my astonishment that it is not one enzyme but an enormous complex of three different enzymatic activities clustered together on a cube-shaped core of 24 units, or alternatively a dodecahedral core of 60 units. The enzymes work together to turn pyruvate into acetyl CoA in a three-step process, handing off to each other as the reaction proceeds.
I enjoyed listening to Michael Lynch's talk on Friday. Much of what he said has been covered in Sandwalk over the past few years. His main point was that nothing in biology makes sense except in the light of population genetics. He laments the fact that most biologists, and even most evolutionary biologists, don't have a firm grasp of population genetics and the importance of random genetic drift.
I asked him why he thought this was true. He said he didn't know why. I think he was being polite. If you read his book, "The Origins of Genome Architecture," you'll see that he attributes this phenomeon to ignorance of modern evolutionary theory.
Here's a link to a remarkable radio interview with Stephen Meyer and Doug Axe. The subject is the Royal Society meeting last November on New trends in evolutionary biology: biological, philosophical and social science perspectives. The theme is not Intelligent Design Creationism, instead it's all about so-called problems with evolutionary theory. That's really what ID is all about in spite of what the IDiots may claim. [see A Royal Pain: Stephen Meyer and Douglas Axe on Five Problems for Evolution.]
Here are the five problems according to IDiots.
"Epigenetics" is the (relatively) new buzzword. Old-fashioned genetics is boring so if you want to convince people (and grant agencies) that you're on the frontlines of research you have to say you're working on epigenetics. Even better, you can tell them that you are on the verge of overthrowing Darwinism and bringing back Jean-Baptiste Lamarck.
But you need to be careful if you adopt this strategy. Don't let anyone pin you down by defining "epigenetics." It's best to leave it as ambiguous as possible so you can adopt the Humpty-Dumpty strategy.1 Sarah C.P. Williams made that mistake a few years ago and incurred the wrath of Mark Ptashne [Core Misconcept: Epigenetics].With a current population size of over 7 billion, the human population should contain a huge amount of genetic variation. Most of it resides in junk DNA so it's of little consequence. We would like to know more about the amount of variation in functional regions of the genome because it tells us something about population genetics and evolutionary theory.
A recent paper in Nature (Aug. 2016) looked at a large dataset of 60,706 individuals. They sequenced the protein-coding regions of all these people to see what kind of variation existed (Lek et al., 2016) (ExAC). The group included representatives from all parts of the world although it was heavily weighted toward Europeans. The authors used a procedure called "principal component analysis" (PCA) to cluster the individuals according to their genetic characteristics. The analysis led to the typical clustering by "population clusters." (That term is used to avoid the words "race" and/or "subspecies.")
De novo genes1 are quite rare but genome duplications are quite common. Sometimes the duplicated regions contain genes so the new genome contains two copies of a gene that was formerly present in only one copy. "Common" in this sense means on a scale of millions of years. Michael Lynch and his colleague have calculated that the rate of fixed gene duplication is about 0.01 per gene per million years (Lynch and Conery, 2003 a,b; Lynch 2007). Since a typical vertebrate has more than 20,000 genes, this means that 200 genes will be duplicated and fixed every million years.
Genome sequencing is becoming so routine that it's difficult to publish your new genome sequence in a top journal. The trick is to find something unique and exciting about your genome so you can attract the attention of the leading journals. The latest success is the seahorse genome published in the Dec. 15, 2016 issue of Nature (Lin et al., 2016.
The species is the tiger tail seahorse Hippocampus comes. The assembled genome is 502Mb or about 1/6th the size of the human genome. The seahorse has 23,458 genes (protein-coding?) or about the same number as most other vertebrates. About 25% of the genome is junk (transposon-related).1
Michael Lynch is giving a seminar next week on Friday, January 13, 2017 in the Dept. of Ecology and Evolutionary Biology at the University of Toronto. The title is: Mutation, Drift, and the Origin of Subcellular Features. The talk is at 3PM in the Earth Sciences Centre rm B142.
I'm a big fan of teaching fundamental concepts and principles and a big fan of teaching critical thinking. I think the most effective way of accomplishing these objectives is some form of student-centered learning. As I near the end of my teaching career, I wonder how we can tell if we succeed? It should be relatively easy to develop an exit exam for our biochemistry/molecular biology students to see if they grasp the basic concepts and can demonstrate an ability to think critically.
Here are some of the questions we could have on that exam. Each one requires a short answer with an explanation. The explanation doesn't have to be detailed or full of facts, just the basic idea. Students are graded on their ability to think critically about the answers. Many of the questions don't have a simple answer. Can you think of any other questions?
A reader alerted me to a paper that was just published in BMC Biology.1 The author is Eugene Koonin. He makes the case for neutral evolution (random genetic drift) and against adaptationism. You may not agree with his take on evolutionary theory but you better be aware of it if you claim to be knowledgeable about evolution.
Koonin, E.V. (2016) Splendor and misery of adaptation, or the importance of neutral null for understanding evolution. BMC biology, 14:114. [doi: 10.1186/s12915-016-0338-2]
The study of any biological features, including genomic sequences, typically revolves around the question: what is this for? However, population genetic theory, combined with the data of comparative genomics, clearly indicates that such a “pan-adaptationist” approach is a fallacy. The proper question is: how has this sequence evolved? And the proper null hypothesis posits that it is a result of neutral evolution: that is, it survives by sheer chance provided that it is not deleterious enough to be efficiently purged by purifying selection. To claim adaptation, the neutral null has to be falsified. The adaptationist fallacy can be costly, inducing biologists to relentlessly seek function where there is none.
Every year John Brockman asks his stable of friends an interesting question. Brockman is a literary agent and most of the people who respond are clients of his. (I want to be one.) The question and responses are posted on his website Edge. This year's question is, "What scientific term or concept ought to be more widely known?"
This year, the introduction is more interesting than the responses. Here's part of what Brokman wrote,
My most popular post last year was: An Intelligent Design Creationist disputes the evolution of citrate utilization in the LTEE ... Lenski responds. It had almost 20,000 views and 227 comments.
The article discussed a paper by Intelligent Design Creationist Scott Minnich who criticized Richard Lenski's ongoing evolution experiment on the grounds that no new information had been created in the evolution of ability to use citrate.
Yesterday I posted an article on: Creationists list the top ten stories of 2016 . Some of you may have noticed that there were only nine stories. That's because Evolution News & Views didn't post their top story until today. I was pretty sure what it would be.
Let me remind you of the main point I made yesterday. Intelligent Design Creationists claim to have scientific evidence of intelligent design. They claim their movement is focused on demonstrating intelligent design but not on proving anything about who the designer might be.Intelligent Design Creationists are still trying to promote their views. They consistently claim to have positive evidence of intelligent design and they consistently complain whenever we point out what they actually do; they attack evolution/science. Their main talking point relies on the fallacy known as "false dichotomy." They assume that by casting doubt on evolution/science they lend support to their religious viewpoint.
Each year, the IDiots on Evolution News & Views (sic) publish their top ten stories. The series is linked to a fund-raising campaign so it's safe to assume they think these stories advance their cause. Let's see how many of the top stories promote intelligent design and how many are just criticisms of evolution/science. That should be revealing ...
