Population Genetics
evolgen | January 9, 2007Imagine you have two races -- because calling them populations is just too damn PC -- that are fixed for different alleles. Additionally, at loci were there are no fixed differences, alleles are segregating at different frequencies between the two races. In order to keep each of the races pure we must prevent any interbreeding (hybridization) between the two races.
Why the hell would we want to keep the races pure? For conservation reasons, of course. You didn't think I was talking about human races, did you? Because I wasn't. Seriously.
The NYTimes is running an article on efforts to…
evolgen | January 8, 2007Phenotypic differences between populations, species, or any other taxonomic classification can be attributed to genetic and environmental causes. The genetic differences can be divided into sequence divergence of transcribed regions, copy number divergence, and expression divergence. These categories are hardly independent -- expression divergence results from the evolution of the protein coding sequences of transcription factors and cis regulatory regions of transcribed sequences.
An article in press in Nature Genetics (news item here) reports on differences in expression of 4,197 genes…
evolgen | January 3, 2007Pim van Meurs has a blog post at The Panda's Thumb about the recent paper on translational selection on a synonymous polymorphic site in a eukaryotic gene (DOI link). He points out that this was predicted in a paper from 1987. In short, the rate of translation depends on the tRNA pool -- amino acids encoded by more abundant tRNA anti-codons will be incorporated more quickly than amino acids with rare tRNAs. Because protein folding begins during translation, codon usage can influence protein secondary structure. That's because rare codons could stall translation, allowing for protein…
evolgen | December 19, 2006John Hawks, along with Gene Expression regular Greg Cochran, has published a paper (PDF) on adaptive introgression in human evolution. In case the jargon is too much, we're talking about the caveman gene. Both Greg and John have blogged the paper. Check out what John says about mtDNA:
However, there have been a growing number of examples of adaptive introgression between different natural populations as well. The use of more nuclear markers has begun to uncover many, but importantly many species have adaptive introgression of mitochondrial DNA.[emphasis from original]
Adaptive introgression…
evolgen | December 2, 2006In the sake of fairness, it's worth reporting that mitochondrial DNA (mtDNA) may not be as flawed as previously thought (see the original paper here). I spent a bit of time earlier this year barking about how mtDNA is a less than stellar marker for inferring demography because it's subject to recurrent selective sweeps which wipe out all signatures of demographic history. Thanks to Dr. Rob, I revised my position to take into account the effects of population size on selection.
If mtDNA mutations are only weakly advantageous, then they should only be under selection in large populations (this…
evolgen | November 23, 2006There's an old paradigm in human population genetics that we each differ from each other by less than one percent at the DNA sequence level. While that may be true for our DNA sequences, recent work indicates that there's also quite a bit of variation amongst individuals in the actual content of their genomes. Such variation is known as copy number variation (CNV) or copy number polymorphism (CNP). What it means is that some people may have one copy of a genomic region, other may have two, and even others may have none.
Nature thinks this research on CNV is quite important, as there are five…
evolgen | November 20, 2006Massimo Pigliucci and Jonathan Kaplan have written a book on evolutionary theory. Check out Massimo's description on his blog. But it's not all masturbatory philosophy -- these guys understand the science. Here's Massimo describing their treatment of adaptive landscapes:
To make the story short (for the longer version you'll have to read the book), Jonathan and I claim that the idea was fraught with problems and inconsistencies from the beginning, and that it has now been radically modified by the work of a mathematical biologist named Sergey Gavrilets. Sergey actually showed that the…
evolgen | November 15, 2006Dan Hartl just finished a two day whirlwind speaking tour at my university (three talks in under 24 hours). He discussed detecting weak selection in protein coding sequences, identifying the underlying genetic causes of phenotypic variation in yeast, and the genetics of malaria parasites. I won't get into the details of these talks, but I will point out one thing Hartl brought up in his first talk that goes well with our recent discussion of computational and wet lab biologists.
The topic is revolutionary developments, the field is population genetics, and the time frame is the past twenty…
evolgen | November 9, 2006In one of the most important papers in population genetics, Begun and Aquadro showed that levels of DNA sequence polymorphism are positively correlated with recombination rate. There are three ways of interpreting this result:
Recombination is mutagenic, and polymorphism is higher with increased mutation.
Positive selection on beneficial mutations decreases levels of linked neutral polymorphism. This effect is greater in regions of decreased recombination and is known as hitchhiking.
Selection against deleterious mutations also decreases linked neutral polymorphism. Like hitchhiking,…
evolgen | November 8, 2006They've finally done it. Bruce Lahn's lab has an article in PNAS (review here) showing evidence for introgression of a gene from an archaic Homo species into the modern human genome. They suggest the possibility that Neanderthals are that archaic species. That's right: there are Neanderthals among us (at least in small portions of our genome).
For those of you interested in the details, here's a brief summary. The gene in question, microcephalin (MCPH1) has an interesting pattern of polymorphism. The approximate coalescence time for all MCPH1 alleles in humans is approximately one million…
evolgen | November 7, 2006A few months ago, JP posted at GNXP that random mating is not necessary for Hardy-Weinberg Equilibrium (HWE). One round of random mating is still sufficient to achieve HWE genotype frequencies, but there are some non-random mating strategies that will also allow for HWE.
HWE is quite robust to violations of the assumptions. That makes it a poor test for things like natural selection, but it is commonly used to detect population structure. If you sample allele and genotype frequencies from a single population, the genotype frequencies should be in HWE. If, however, you sample from two separate…
evolgen | October 12, 2006The most important nail was hammered in by this article -- a symbolic slap across the face to anyone who uses mtDNA, and mtDNA only, to study demography. An upcoming article in BMC Biology lays down another nail:
A study published today in the open access journal BMC Biology reveals that fewer than 10% of African American mitochondrial DNA sequences analysed can be matched to mitochondrial DNA from one single African ethnic group. There has been a growing interest in the use of mitochondrial DNA to trace maternal ancestries, and several companies now offer to analyse individuals'…
evolgen | October 9, 2006Dr. Rob weighs in on the lack of a relationship between mitochondrial DNA (mtDNA) polymorphism and population size. To recap: DNA polymorphism should predict population size -- larger populations will have more polymorphism than small populations. Additionally, comparing different measures of polymorphism allow us to infer ancient demographic events. But natural selection can also shape DNA polymorphism. Positive (or Darwinian) selection will drive an advantageous allele to fixation, taking linked neutral variants along with it. This selective sweep will decrease polymorphism in a region…
evolgen | October 7, 2006People like dogs. They're man's best friend, after all. There are tons of different breeds, many of which could be classified as unique species if we didn't know better. Our interest in dogs has led to lots of studies into dog breeding, figuring out which genes gave rise to the different morphologies, and determining the evolutionary history of dogs.
The history we're most familiar with is that of domesticated wolves. That is, thousands of years ago, human populations tamed wild wolves, and those animals eventually gave rise to the dogs we know today. I'll admit, I thought that's where the…
evolgen | September 30, 2006Via Yann Klimentidis come this paper comparing patterns of polymorphism in mitochondrial DNA (mtDNA) and Y chromosomes from Native American populations. The premise is that mtDNA reveals the maternal demographic history (because mitochondria are only passed from mother to child) of a population and the Y chromosome reveals the paternal history (Y chromosomes are only passed from father to son). But we know that mtDNA is not a good marker for studying demographic history because there is no recombination in the mitochondrial genome. That means that evidence of demographic events will be swept…
sporte | September 27, 2006We went on an excursion last weekend to see the Dead Sea Scrolls at the Pacific Science Center. None of us could resist going downtown to look at written texts over 2000 years old. Uncovered in 1946, by a Bedouin shepherd, the scrolls have had an interesting history over the past 50 years, most of it out of the public eye. Only recently, have a large number of scholars and members of the public been granted access.
We're still kind of amazed that they came to Seattle.
I'm fascinated by archeology, but I was also interested in how DNA analysis is being used to study the scrolls and…
sporte | September 26, 2006Razib inspired me to share some of the story behind why white people are considered derivatives.
Reposted from the Classic Digital Bio.
No red herrings, here! Lamason et. al. found a single gene that controls human skin color while studying pigmentation in zebra fish (1).
These zebra fish had an unusual golden color that turned out to be an important clue. Lamason and collaborators found that the golden zebra fish lost their normal color because of a mutation in the slc24a5 gene. When the zebra fish have the mutant form, they produce fewer melanosomes.
A short language lesson
Fewer…
evolgen | September 20, 2006Over a year and half ago (~1 eon in internet time) I wrote this blog entry in which I turned around the title of Dobzhansky's famous essay "Nothing in Biology Makes Sense Except in the Light of Evolution". I didn't think I was being all that clever when I came up with the following:
NOTHING IN EVOLUTION MAKES SENSE EXCEPT IN THE LIGHT OF GENETICS
I pointed out that evolution requires heritable variation first and foremost, hence genetics lies at the center of all of evolution. I then took the opportunity to explain why Hardy and Weinberg's derivation that random mating does not change allele…
evolgen | September 18, 2006Adam Eyre-Walker has published a review of adaptive evolution in a few well studied systems: Drosophila, humans, viruses, Arabidopsis, etc. These organisms have been the subject of many studies that used DNA polymorphism, DNA divergence, or a combination of the two to detect natural selection in both protein coding and non-coding regions of the genomes. Now that we have whole genome sequences for multiple closely related species from a few different taxa, many researchers are interested in determining the role of natural selection in the evolution of DNA sequences.
Eyre-Walker claims that the…
sporte | August 23, 2006Did HIV become resistant to Atazanavir because of a genetic change?
Was that genetic change inherited?
Did HIV evolve?
Can we explain why genetic changes at specific sites might help HIV escape the effects of the drug?
Let's find out.
All of the sequences in the image below (except for the first) come from HIV strains that were isolated from patients who took Atazanavir and no other protease inhibitors. All of the strains of HIV from patients were resistant to the drug.
If an amino acid is different from other strains, the color at that position is changed. Since we see different…