29 October 2017

An overnight recipe for a new gene: change the frame

Can a new protein-coding gene be born overnight? That's the theme of this series. The answer, remarkably, is yes, and the Arhgap11b gene is the recent case I'm considering. After surveying the ways that this could happen, I narrowed the possible mechanisms to three:
There are really just three kinds of change that can get it done. All three are mutations that change how the DNA sequence that's already there gets decoded into protein. They are: 1) tiny mutations that shift the reading frame; 2) tiny mutations that change splicing; and 3) large-ish rearrangements that create new combinations of code.
Before looking at the details, let's take note of the fact that the genomes of animals and plants typically have gigantic amounts of DNA that does not code for protein. Humans are merely typical in this regard—at least 95% of the human genome is non-coding DNA, but there are organisms with a lot more and some with a lot less. The point here is not about "junk" or function, it's more basic: an animal genome contains vast amounts of DNA that could code for a protein, but doesn't. A new gene doesn't have to be magicked into a genome, by a demon or by a virus. A new gene can enter the gene library simply by becoming a new way of reading a pre-existing text. This is almost certainly how the vast majority of new genes have arisen in animals and plants for at least half a billion years. And the basic mechanism applies to all living things, for 3-ish billion years: any DNA sequence can become a protein-coding sequence, and those that already do code for protein can be straightforwardly modified to make completely different proteins.

16 September 2017

Gene-making: some questions answered

In my previous post I attempted to identify all the ways that a new gene can come about, after defining what I meant by "new" and "gene." Two questions came up, one a comment on the post, and the other via Facebook.

1. What about exon shuffling? Isn't that a mechanism by which new genes are made?

Exon shuffling is, roughly, the creating of new coding sequences (genes, as I'm defining them in this series) by the rearrangement of pieces of coding sequence. (An exon is a piece of coding sequence in DNA or RNA.) It's a nice descriptive phrase: the exons are gene pieces, and they can be moved around to make new cominbations that code for new proteins. So is this an additional mechanism for the creation of genes?

No, it's not.

10 June 2017

Can someone make me a new gene?

What would it take to make a completely new gene?

Interesting question, but first let's agree on roughly what we mean by a "new gene." Here is how I defined the topic when discussing unique human attributes:
A truly new and unique human gene, for my purposes here, would be a gene that makes a protein that is unique to humans—a protein never before seen, not something merely tweaked from a precursor.
"Creation of Eve." Was she completely new?
So you see we mean something a lot more "new" than, for example, the human-specific version of the FoxP2 gene, which I have discussed before. And we mean something that is born overnight. After all, incremental changes over eons can result in a gene being transformed into something utterly different. That's interesting, of course, but it's not what we mean by a "new gene." We are discussing genes that appear suddenly and code for protein, and we want them to truly "appear" and not merely move from one species to another.

14 May 2017

Does it take special genes to make a special human?

We humans think we're pretty special. Here's Hamlet, in the speech that gave this blog its name:
What a piece of work is a man! How noble in reason! how infinite in faculty! in form, in moving, how express and admirable! in action how like an angel! in apprehension how like a god! the beauty of the world! the paragon of animals!

Hamlet, Act II, Scene II, The Oxford Shakespeare
Kemble in the role of Hamlet, from Wellcome Images.
Kemble in the role of Hamlet.
Courtesy of Wellcome Images.
It is common, at least in the West, to consider humans "the paragon of animals," typically making reference to the ancient idea of "God's image." I won't address here whether humanity is a paragon, but here's a more tractable question: what are the facets that distinguish humans from other animals? Biologically speaking, what is special about humans that sets them apart from other apes?

Anatomically, we're pretty unremarkable apes. We have enlarged gluteal muscles and other adaptations that make us good distance runners. We have fancy thumbs that make us good tool users. We have a tweaked larynx that facilitates speech. We have spineless penises that facilitate other things. And of course we have what Hamlet was talking about: big brains and associated cognitive abilities.

01 March 2017

A mystery gene in human brain development: discovering ARHGAP11b

The human brain is often described using literally cosmic superlatives. Here is V.S. Ramachandran, a renowned neuroscientist:
The human brain, it has been said, is the most complexly organised structure in the universe and to appreciate this you just have to look at some numbers. The brain is made up of one hundred billion nerve cells or "neurons" which is the basic structural and functional units of the nervous system. Each neuron makes something like a thousand to ten thousand contacts with other neurons and these points of contact are called synapses where exchange of information occurs. And based on this information, someone has calculated that the number of possible permutations and combinations of brain activity, in other words the numbers of brain states, exceeds the number of elementary particles in the known universe.
That's some serious complexity there, yes, but hidden in the description is a mundane reality: the human brain is made of neurons which make synapses with other neurons, which means that it's made of the same stuff as the brain of a sloth or a goldfish or an earthworm. (Or even a parasitic mite on an earthworm.) Still, whether or not the human brain is really special or just big, something has caused it to grow in ways that differ from its predecessors. Especially at key junctures in the process, human brain development must depart from boring old mammalian brain development. And this should be reflected by — and perhaps explained by — patterns of gene expression.

20 February 2017

When a GAP is not a GAP: ARHGAP11B, the mysterious human-specific gene

A truly human-specific gene, not merely a human-specific version of an animal gene or a mammal gene or a primate gene — that is something particularly interesting. Given that the human genome is 96% identical to that of our closest relatives (chimps and bonobos), and given that so much of those genomes is composed of mobile elements that are unlikely to end up being genes at all, I and perhaps others long thought that human-specific genes would be something pretty rare.

But there they are — genes by every definition, that code for protein and are expressed in human tissues, that are unique in humans. One of the most interesting is a gene that brings together some of my personal favorite topics in biology: brain development, cellular signaling systems, and of course evolution. The gene goes by the unfortunate "name" of ARHGAP11B.

I do consider ARHGAP11B to be a unique human gene, but its name betrays its evolutionary history and its membership in a family of genes, so it's not completely unique (specifics to come). That family is the family of GAPs, a group of proteins that were the focus of my postdoctoral research years ago. GAP stands for "GTPase-activating protein," and besides being a typical morsel of biochemical jargon, the phrase is a bit of an insult to the roles played by these proteins in cellular signaling systems.

04 January 2017

Relaunch in 10...9...8...

Quintessence of Dust has been on hiatus for more than five years. It's time to resurrect it. Why now? Because it's 2017, and 2017 is not a time to be quiet.

The first project involves some remodeling. Quintessence of Dust was built almost ten years ago, with a set of themes and goals that don't all fit in 2017. Most notably, the blog was conceived when I was a Christian, and for five years addressed issues and questions that I knew to be of interest to evangelical Christians. I am happily no longer a Christian, and will remodel the blog to reflect that. I do still live in the United States, in 2017, where evangelical Christianity exerts significant influence. And I know a lot about that world. So religion will be an occasional, if tangential, topic. But now I will write as a skeptic, as one who has transitioned from Christian humanism to just plain humanism. The remodeling of the site is mostly to make this clear. I do think I'll keep the Celtic cross in the banner.

In parallel with the remodeling I'll start writing about cool science. And I've already found the topic of my first post or two: a paper from last month that identifies a single mutation in the human genome that may explain (at least in part) the dramatic expansion of the cerebral cortex that occurred in our lineage. The story is a remarkable confluence of topics very dear to me: evolution, developmental neurobiology, and cellular signaling systems. The protein at the center of the story is closely related to the proteins that I spent my postdoctoral fellowship trying to understand. I'll explain all of this in the posts to come.

If you want to have a peek at the story, check out the news piece at the BBC, or the new paper itself (it's open access). The first part of the saga, in which the protein's role in brain development was discovered, was published in 2015 (also open access but requires free registration).

Image: By Internet Archive Book Images [No restrictions], via Wikimedia Commons