Monday, January 23, 2017

Why does the human population carry an allele that increases the risk of Alzheimer's?

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.

The second reason is that the slight deleterious effect, if there is one from an evolution perspective, may not have been significant enough in small populations. I know, and I hope my students know, that neutral and deleterious alleles can reach significant frequency in a population by chance. The general public doesn't know this.

Check out Ed Yong's article to see his explanation.
“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.”

Thursday, January 19, 2017

The pervasive transcription controversy: 2002

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.

Wednesday, January 18, 2017

Pyruvate dehydrogenase astonishes Ann Gauger

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.

Sunday, January 15, 2017

Why are most biologists adaptationists?

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.

Saturday, January 14, 2017

The dynamic duo tell us about five problems with evolution

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.
  1. Fossil record (Cambrian explosion)
  2. The origin of information (no known natural source of information)
  3. The necessity of early mutations (you can't mutate regulatory genes that act early in development because all mutations in those genes are lethal)
  4. Epigenetic information (you can't evolve new body plans by mutating DNA because development is controlled by non-DNA epigenetic information)
  5. The universal design intuition that we all have (everybody thinks that people are created by a god-like designer, even atheists, so it must be true)

Saturday, January 07, 2017

What the heck is epigenetics?

"Epigenetics" is the (relatively) new buzzword. Old-fashioned genetics is boring so if you want to convince people (and grant agencies) 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].

Friday, January 06, 2017

Genetic variation in the human population

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.")

Thursday, January 05, 2017

Birth and death of genes in a hybrid frog genome

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.

The initial duplication event is likely to be deleterious since there will now be redundant DNA in the genome. The slightly deleterious allele (duplication) can be purged by negative selection in species with large population sizes (e.g. bacteria). But in species with smaller populations, natural selection is not powerful enough to eliminate slightly deleterious alleles so the duplication persists and may become fixed in the population.

Wednesday, January 04, 2017

Do seahorses evolve faster?

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

Tuesday, January 03, 2017

Save the date!!! Michael Lynch is coming to Toronto

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.

The exit exam for biochemistry and molecular biology students

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?

Monday, January 02, 2017

You MUST read this paper if you are interested in evolution

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.

The Edge question 2017

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,

Sunday, January 01, 2017

The most popular Sandwalk post of 2016

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.

Intelligent Design Creationists reveal their top story of 2016

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.

But that's not what the movement is all about. Most of their writings and speeches are focused on attacking evolution. They hope that by discrediting evolution and science they will, by default, support the case for gods (false dichotomy). They also hope that by promoting gaps in our knowledge they will lend support to those who want to insert gods into the gaps.

You don't need to take my word for it. Just look at what they think are the top stories of 2016. Most of their top nine stories were critiques of science in one way or another. There wasn't a single top story that advanced the case for intelligent design.

So, what about the #1 story? Is it going to be different?