The Pith: Evolution is a sloppy artist. Upon the focal zone of creative energy adaptation can sculpt with precision, but on the margins of the genetic landscape frightening phenomena may erupt due to inattention. In other words, there are often downsides to adaptation.
A few weeks ago I reviewed a paper which suggests that Crohn’s disease may be a side effect of a selective sweep. The sweep itself was possibly driven by adaptation to nutrient deficiencies incurred by European farmers switching to a grain based diet. The reason for this is a contingent genomic reality: the positively selected genetic variant was flanked by a Crohn’s disease risk allele. The increment of fitness gain of the former happens to have been greater than the decrement entailed by the latter, resulting in the simultaneous increase in the frequency of both the fit and unfit variants. You can’t always have one without the other.
But that’s just focusing on one gene, though the authors did indicate that this may be a genome-wide feature. A new paper in PLoS Genetics argues that that is the case, at least to some extent. Evidence for Hitchhiking of Deleterious Mutations within the Human Genome:
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: What makes rice nice in one varietal may not make it nice in another. Genetically that is….
Rice is edible and has high yields thanks to evolution. Specifically, the artificial selection processes which lead to domestication. The “genetically modified organisms” of yore! The details of this process have long been of interest to agricultural scientists because of possible implications for the production of the major crop which feeds the world. And just as much of Charles Darwin’s original insights derived from his detailed knowledge of breeding of domesticates in Victorian England, so evolutionary biologists can learn something about the general process through the repeated instantiations which occurred during domestication during the Neolithic era.
A new paper in PLoS ONE puts the spotlight on the domestication of rice, and specifically the connection between particular traits which are the hallmark of domestication and regions of the genome on chromosome 3. These are obviously two different domains, the study and analysis of the variety of traits across rice strains, and the patterns in the genome of an organism. But they are nicely spanned by classical genetic techniques such as linkage mapping which can adduce regions of the genome of possible interesting in controlling variations in the phenotype.
In this paper the authors used the guidelines of the older techniques to fix upon regions which might warrant further investigation, and then applied the new genomic techniques. Today we can now gain a more detailed sequence level picture of the genetic substrate which was only perceived at a remove in the past through abstractions such as the ‘genetic map.’ Levels and Patterns of Nucleotide Variation in Domestication QTL Regions on Rice Chromosome 3 Suggest Lineage-Specific Selection:
I was semi-offline for much of last week, so I only randomly heard from someone about the “Science paper” on which Molly Przeworski is an author. Finally having a chance to read it front to back it seems rather a complement to other papers, addressed to both man and beast. The major “value add” seems to be the extra juice they squeezed out of the data because they looked at the full genomes, instead of just genotypes. As I occasionally note the chips are marvels of technology, but the markers which they are geared to detect are tuned to the polymorphisms of Europeans.
Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of “classic selective sweeps” (in which a beneficial mutation arises and rapidly fixes in the population). Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past ~250,000 years.