- Life Technologies/Ion Torrent apparently hires d-bag bros to represent them at conferences. The poster people were fine, but the guys manning the Ion Torrent Bus were total jackasses if they thought it would be funny/amusing/etc. Human resources acumen is not always a reflection of technological chops, but I sure don’t expect organizational competence if they (HR) thought it was smart to hire guys who thought (the d-bags) it would be amusing to alienate a selection of conference goers at ASHG. Go Affy & Illumina!
- Speaking of sequencing, there were some young companies trying to pitch technologies which will solve the problem of lack of long reads. I’m hopeful, but after the Pacific Biosciences fiasco of the late 2000s, I don’t think there’s a point in putting hopes on any given firm.
- I walked the poster hall, read the titles, and at least skimmed all 3,000+ posters’ abstracts. No surprise that genomics was all over the place. But perhaps a moderate surprise was how big exomes are getting for medically oriented people.
- Speaking of medical/clinical people, I noticed that in their presentations they used the word ‘Caucasian‘ a lot. This was not evident in the pop-gen folks. It shows the influence of bureaucratic nomenclature in modern medicine, as they have taken to using somewhat nonsensical US Census Bureau categories.
- Twitter was a pretty big deal. There were so many interesting sessions that I found myself checking my feed constantly for the #ASHG2012 hashtag. It was also an easy way to figure out who else was at the same session (e.g., in my case, very often Luke Jostins).
- If you could track the patterns of movements of smartphones at the conference it would be interesting to see a network of clustering of individuals. For example, the evolutionary and population genomics posters were bounded by more straight-up informatics (e.g., software to clean your raw sequence data), from which there was bleed over. But right next to the evolution and population genomics sections (and I say genomics rather than genetics, because the latter has been totally subsumed by the former) you had some type of pediatric disease genetics aisles. I wasn’t the only one to have a freak out when I mistakenly kept on moving (i.e., you go from abstruse discussions of the population structure of Ethiopia, to concrete ones about the likely probability of death of a newborn with an autosomal dominant disorder, with photos of said newborn!).
OK, perhaps I can help with that. Dr. Coop speaks of the collaboration between himself & Dr. Joseph Pickrell, Haldane’s Sieve, which I added to my RSS days ago (and you can see me pushing it to my Pinboard). From the “About”:
As described above, most posts to Haldane’s Sieve will be basic descriptions of relevant preprints, with little to no commentary. All posts will have comment sections where discussion of the papers will be welcome. A second type of post will be detailed comments on a preprint of particular interest to a contributor. These posts could take the style of a journal review, or may simply be some brief comments. We hope they will provide useful feedback to the authors of the preprint. Finally, there will be posts by authors of preprints in which they describe their work and place it in broader context.
We ask the commenters to remember that by submitting articles to preprint servers the authors (often biologists) are taking a somewhat unusual step. Therefore, comments should be phrased in a constructive manner to aid the authors.
It might be helpful if other evolution/genetics bloggers reblog this so we can push it up the Google search results. If you google “Haldane’s Sieve” some of the results are interesting…and not necessarily in a good way. I do feel guilt blogging on stuff my readers can’t get, so the more preprints become acceptable the more we (as in, the general public) can understand about evolution.
The Pith: Natural selection is a quick & dirty operator. When subject to novel environments it can react rapidly, bringing both the good and the bad. The key toward successful adaptation is not perfection, but being better than the alternatives. This may mean that many contemporary diseases are side effects of past evolutionary genetic compromises.
The above is a figure from a recent paper which just came out in Molecular Biology and Evolution, Crohn’s disease and genetic hitchhiking at IBD5. You probably have heard about Crohn’s disease before, there are hundreds of thousands of Americans afflicted with it. It’s an inflammatory bowel ailment, and it can be debilitating even to very young people. The prevalence also varies quite a bit by population. Why? It could be something in the environment (e.g., different diet) or genetic predisposition, or some combination. What the figure above purports to illustrate is the correlation between Crohn’s disease and the expansion of the agricultural lifestyle.
But don’t get overexcited Paleos! There are many moving parts to this story, and I need to back up to the beginning. The tens of thousands of genes which you inherited from your parents are embedded within the genome and aligned in a set of sequences, one after the other. On the one hand for the purposes of conceptualizing evolutionary dynamics, such as natural selection or random genetic drift, focusing on a single gene is useful. It has power to illustrate some basic and elementary principles. But sometimes you need to take a more synoptic view, and look at genes in their broader context. In this post I’ll avoid molecular or statistical epistasis, gene-gene interaction. Rather, let’s just consider the static landscape of the genome, where genes are physical concrete entities which are embedded in a particular spatial relationship to other genes, upstream or downstream in the genetic code. These physical or statistical associations of genes can form a de facto supergene through linkage, and their variants combine to form haplotypes, sequences of markers across small stretches of the genome. But recall that these associations are counter-balanced by genetic recombination, which tears apart physical sequences and sows them to the opposite DNA strand.
The Pith: The human X chromosome is subject to more pressure from natural selection, resulting in less genetic diversity. But, the differences in diversity of X chromosomes across human populations seem to be more a function of population history than differences in the power of natural selection across those populations.
In the past few years there has been a finding that the human X chromosome exhibits less genetic diversity than the non-sex regions of the genome, the autosome. Why? On the face of it this might seem inexplicable, but a few basic structural factors derived from the architecture of the human genome present themselves.
First, in males the X chromosome is hemizygous, rendering it more exposed to selection. This is rather straightforward once you move beyond the jargon. Human males have only one copy of genes which express on the X chromosome, because they have only one X chromosome. In contrast, females have two X chromosomes. This is the reason why sex linked traits in humans are disproportionately male. For genes on the X chromosome women can be carriers of many diseases because they have two copies of a gene, and one copy may be functional. In contrast, a male has only a functional or nonfunctional version of the gene, because he has one copy on the X chromosome. This is different from the case on the autosome, where both males and females have two copies of every gene.
This structural divergence matters for the selective dynamics operative upon the X chromosome vs. the autosome. On the autosome recessive traits pay far less of a cost in terms of fitness than they do on the X chromosome, because in the case of the latter they’re much more often exposed to natural selection via males. In the rest of the genome recessive traits only pay the cost of their shortcomings when they’re present as two copies in an individual, homozygotes. A simple quasi-formal example illustrates the process.
The Pith: In this post I review a paper which covers the evolutionary dimension of human childbirth. Specifically, the traits and tendencies peculiar to our species, the genes which may underpin those traits and tendencies, and how that may relate to broader public health considerations.
Human babies are special. Unlike the offspring of organisms such as lizards or snakes human babies are exceedingly helpless, and exhibit an incredible amount of neoteny in relation to adults. This is true to some extent for all mammals, but obviously there’s still a difference between a newborn foal and a newborn human. One presumes that the closest analogs to human babies are those of our closest relatives, the “Great Apes.” And certainly the young of chimpanzees exhibit the same element of “cuteness” which is appealing to human adults. Still there is a difference of degree here. As a childophobic friend observed human infants resemble “larvae.” The ultimate and proximate reason for this relative underdevelopment of human newborns is usually attributed to our huge brains, which run up against the limiting factor of the pelvic opening of women. If a human baby developed for much longer through extended gestation then the mortality rates of their mothers during childbirth would rise. Therefore natural selection operated in the direction it could: shortening gestation times. You might say that in some ways then the human newborn is an extra-uterine fetus.
A new paper in PLoS Genetics attempts to fix upon which specific genomic regions might be responsible for this accelerated human gestational clock. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing:
The Pith: I review a recent paper which argues for a southern African origin of modern humanity. I argue that the statistical inference shouldn’t be trusted as the final word. This paper reinforces previously known facts, but does not add much that both novel and robust.
I have now read the paper which I expressed a touch of skepticism toward yesterday. Do note, I did not dispute the validity of their results. They seem eminently plausible. I was simply skeptical that we could, with any level of robustness, claim that anatomically modern humans arose in southern vs. eastern, or western, Africa. If I had to bet, my rank order would be southern ~ eastern > western. But my confidence in my assessment is very low.
First things first. You should read the whole paper, since someone paid for it to be open access. Second, much props to whoever decided to put their original SNP data online. I’ve already pulled it down, and sent off emails to Zack, David, and Dienekes. There are some northern African populations which allow us to expand beyond the Mozabites, though unfortunately there are only 55,000 SNPs in that case (I haven’t merged the data, so I don’t know how much will remain after combining with HapMap or HGDP data set).
Mitochondrial DNA from 147 people, drawn from five geographic populations have been analysed by restriction mapping. All these mitochondrial DMAs stem from one woman who is postulated to have lived ab7out 200,000 years ago, probably in Africa. All the populations examined except the African population have multiple origins, implying that each area was colonised repeatedly
And so was published in the year 1987 the paper which established in the public’s mind the idea of mitochondrial Eve, which gave rise to a famous cover photo in Newsweek. This also led to the Children of Eve episode on the PBS documentary NOVA. Here is the summary:
NOVA examines a controversial theory that traces our ancestry to a small group of women living in Africa 300,000 years ago.
As Milford Wolpoff has complained it is probably accurate to characterize the documentary as not particularly “fair & balanced.” Mitochondrial Eve may have been controversial, and subsequently plagued by issues of molecular clock calibration as well as spurious interpretations of the cladograms, but the tide of history was on its side, and PBS was telling that story. And the story was not just the primary science, rather, one had to understand the controversy in light of the debates among paleontologists and between paleontologists and molecular biologists. A group of researchers, spearheaded by Chris Stringer argued for the recent origin of modern humans from Africa on the basis of fossils alone. They were challenged by an established school of multiregionalists who argued for deeper roots of modern human populations, which derived from local hominins which diversified after the the migration of H. erectus out of Africa. The argument of the multiregionalists was that selective sweeps across the full range of the human populations gave rise gradually to modern humanity as we know it, a compound of specific ancient local features and trans-population characters which unified us into a broader whole. Stringer and company presented a simpler model where anatomically modern human being arose ~200,000 years ago in Africa, and subsequently expanded to other parts of the world, by and large replacing the local hominin populations. In the multiregionalist telling Neandertals became human beings, while Out of Africa would imply that Neandertals were replaced by human beings.
A month ago I pointed to a short communication in Nature Genetics which highlighted differences in the patterns of variation between the X chromosome and the autosome. I thought it would be of interest to revisit this, because it’s a relatively short piece with precise and crisp results which we can ruminate upon.
Sometimes there is a disjunction between how evolutionary biologists and molecular biologists use terms like “gene.” The issue is explored in depth in Andrew Brown’s The Darwin Wars. Brown observes that one of the problems with Richard Dawkins’ style of exposition is that it did not translate well to the American context. He spoke of genes as units of analysis, from which logical inferences could be made. This was the classical Oxford style of evolutionary biology which Ernst Mayr objected to. In contrast American biologists were used to thinking of genes in more concrete biophysical terms, and tended to miss the theoretical context which Dawkins was alluding to in his arguments. In Dawkins’ defense, it must be remembered that the gene does have its origins as an abstract entity whose biophysical substrate, DNA, was not known for decades. In my post Simple rules for inclusive fitness I outlined a paper which is very much in keeping with the analytic tradition. Start with an abstract model and allow the chain of inferences to be made, and see where it takes you.