HERC2 and eye color variation

OCA2 has been the one of the main genes thought to be responsible for eye color variation (see here). Now, two papers in AJHG (open access, here, here) show that SNPs in HERC2 may represent the strongest association with eye color. Dienekes and Razib have also covered these papers, including some maps of HERC2 SNP frequencies across Europe. Razib did some further digging and found a paper where they used cell culture to determine that a HERC2 SNP causes changes to OCA2 promoter activity... now we're getting somewhere! By the way, HERC2 is very close to OCA2 on chr. 15, and that region has been under recent selection in Europeans.
from the first abstract:

Testing markers in the HERC2-OCA2 region may be useful in forensic applications to predict eye color phenotypes of unknown persons of European genetic origin.

from the second abstract:

We conclude that the conserved region around rs12913832 (of HERC2) represents a regulatory region controlling constitutive expression of OCA2 and that the C allele at rs12913832 leads to decreased expression of OCA2, particularly within iris melanocytes, which we postulate to be the ultimate cause of blue eye color.

Interestingly in the Kayser paper, none of the other candidate genes (MATP, ASIP, CYP1A2, TYRP1, CYP2C8, and CYP2C9 showed any association.
These studies makes you wonder about similar confounding (eg. hitchhiking) in other phenotype-genotype associations. Resolving this seems to require a combination of large independently replicated WGA studies, functional assays, as well as looking for what other genes lie in the regions of strong selection signals.
One also wonders if the effects of these loci are independent of variation in other pigmentation related traits.
I also wondered if they examined if there was the potential for confounding due to population stratification (which can happen in Europeans). It looks like they did in the Kayser paper, although I'm unclear about exactly how they did it, and in the Sturm paper, they say that 95% of subjects are of N. European origin. Related to this, Kayser et al. warn at the very end of their paper:

However, until more data become available, such a DNA-based iris color prediction test shall only be considered in individuals of whom a European genetic origin has been verified with appropriate ancestry-informative genetic markers.

Journal impact factors from Scimago

Thomson Scientific has been the main source of journal rankings/impact factors. Here's a link to a new company called SCImago that is doing the same thing. It uses data from Scopus and applies the Google PageRank algorithm. Their website is very user friendly, so check it out next time you're deciding between submitting your paper to Science or to Nature ;) ... (neither of which are particularly high on the rankings)

What's up with selection on olfactory genes in humans?

Several genome scans for selection in humans find strong signals around olfactory-related genes, which is counter-intuitive since humans are relatively unreliant on smell compared to other mammals (primates?). Or are they? ... some explanations include:

• P-ter at GNXP has discussed this issue, and points us to this paper in PLoS Biology arguing that our sense of smell may actually be really good, and to another paper that we can actually be very good scent trackers.

• I also remember reading somewhere a long time ago that the odor that humans are most sensitive to is beta-mercaptol (or something like that) which is found in rotting meat.

• There's also a possible sexual selection argument, such that appropriate/compatible mate choice is more important in humans than in chimps and other primates, and we know that mate choice is mediated by olfactory signals.

• It has also been found that these signatures of selection may be recent and may differ between ethnic groups, as seen in this paper on the dynamics of admixture and selection in Puerto Rican, where they also point out that HLA genes are nearby the olfactiory genes, possibly confounding these findings.

This area is pretty ripe with testable hypotheses, using phenotypic and genotypic data, that could inform us about various aspects of human reproductive and feeding ecology.

There's a new paper (see abstract below) on OR511, one of the top fifty human genes showing evidence of positive selection (based on synonymous vs. non-synonymous substitutions). They look at SNPs in this gene from 39 human populations. They confirm a signature of selection, show that it doesn't vary between populations, and that selection on this gene was likely spurred before the dispersal of humans out of Africa.
They don't really give any human-specific explanation for selection on olfactory genes.

Signatures of Selection in the Human Olfactory Receptor OR5I1 Gene
Andrés Moreno-Estrada, Ferran Casals, Anna Ramírez-Soriano, Baldo Oliva, Francesc Calafell, Jaume Bertranpetit, and Elena Bosch,
Molecular Biology and Evolution 2008 25(1):144-154

Abstract: The human olfactory receptor (OR) repertoire is reduced in comparison to other mammals and to other nonhuman primates. Nonetheless, this olfactory decline opens an opportunity for evolutionary innovation and impirovement. In the present study, we focus on an OR gene, OR5I1, which had previously been shown to present an excess of amino acid replacement substitutions between humans and chimpanzees. We analyze the genetic variation in OR5I1 in a large worldwide human panel and find an excess of derived alleles segregating at relatively high frequencies in all populations. Additional evidence for selection includes departures from neutrality in allele frequency spectra tests but no unusually extended haplotype structure. Moreover, molecular structural inference suggests that one of the nonsynonymous polymorphisms defining the presumably adaptive protein form of OR5I1 may alter the functional binding properties of the OR. These results are compatible with positive selection having modeled the pattern of variation found in the OR5I1 gene and with a relatively ancient, mild selective sweep predating the "Out of Africa" expansion of modern humans.

Differential gene expression can make a difference in morphology

This study is the first to show it (abstract below). These researchers put part of an enhancer of the gene Prx1 from a bat into mice, and they find that the mice displayed longer forelimbs, albeit only 6% longer. Theoretically, this could be an example of one step out of many small ones on the way towards developing the ability for flight.
Another interesting finding was that when they deleted the Prx1 enhancer in the mouse, they didn't find any immediate effects on forelimb length, "revealing regulatory redundancy", according to the authors.

Via this bit in Science.

Regulatory divergence modifies limb length between mammals
Chris J. Cretekos, Ying Wang, Eric D. Green, James F. Martin, John J. Rasweiler IV, and Richard R. Behringer
Genes and Development 22:141-151, 2008

Abstract: Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis-regulatory redundancy may facilitate accumulation of such mutations.

Post-copulatory MHC dis-assortative mating

Diversity in immune genes via appropriate mate choice was likely highly selected for and this has been shown to some extent in behaviors among human females who prefer the smells and cheat less on men who have more dissimilar HLA (human version of MHC) genetic profiles. Most of this kind of stuff is coming out of UNM.

Compatibility counts: MHC-associated mate choice in a wild promiscuous primate

Nina Schwensow, Manfred Eberle, Simone Sommer
Proceeding of the Royal Society, B Volume 275, Number 1634 / March 07, 2008

Abstract: The mechanisms and temporal aspects of mate choice according to genetic constitution are still puzzling. Recent studies indicate that fitness is positively related to diversity in immune genes (MHC). Both sexes should therefore choose mates of high genetic quality and/or compatibility. However, studies addressing the role of MHC diversity in pre- and post-copulatory mate choice decisions in wild-living animals are few. We investigated the impact of MHC constitution and of neutral microsatellite variability on pre- and post-copulatory mate choice in both sexes in a wild population of a promiscuous primate, the grey mouse lemur (Microcebus murinus). There was no support for pre-copulatory male or female mate choice, but our data indicate post-copulatory mate choice that is associated with genetic constitution. Fathers had a higher number of MHC supertypes different from those of the mother than randomly assigned males. Fathers also had a higher amino acid distance to the females' MHC as well as a higher total number of MHC supertypes and a higher degree of microsatellite heterozygosity than randomly assigned males. Female cryptic choice may be the underlying mechanism that operates towards an optimization of the genetic constitution of offspring. This is the first study that provides support for the importance of the MHC constitution in post-copulatory mate choice in non-human primates.

The genetic puzzle of coat color and fitness in Soay sheep

There are dark sheep and light sheep. The dark sheep are bigger, and bigger sheep tend to have higher fitness (survival and reproductive success)...but their frequency has gone down over the past 20 years. what gives? - their findings suggest "a negative genetic correlation between size and fitness in the vicinity of TYRP1" due to either pleiotropy or LD with surrounding loci for which they give some candidate genes that have been found to have the relevant effects in mice: neonatal size via VLDLR and "brown-associated fitness" via PTPRD. This gene, TYRP1, is very convenient for this study because it has been shown to control most of the variation in sheep coat color.
The implications here are important but, I think we also need to ask why we find the specific combinations of pleiotropic effects or the patterns of LD that we find. For example why is tameness apparently genetically linked to coat color in foxes (here, here)?

A Localized Negative Genetic Correlation Constrains Microevolution of Coat Color in Wild Sheep
J. Gratten, A. J. Wilson, A. F. McRae, D. Beraldi, P. M. Visscher, J. M. Pemberton, J. Slate
Science 18 January 2008: Vol. 319. no. 5861, pp. 318 - 320

The evolutionary changes that occur over a small number of generations in natural populations often run counter to what is expected on the basis of the heritability of traits and the selective forces acting upon them. In Soay sheep, dark coat color is associated with large size, which is heritable and positively correlated with fitness, yet the frequency of dark sheep has decreased. This unexpected microevolutionary trend is explained by genetic linkage between the causal mutation underlying the color polymorphism and quantitative trait loci with antagonistic effects on size and fitness. As a consequence, homozygous dark sheep are large, but have reduced fitness relative to phenotypically indistinguishable dark heterozygotes and light sheep. This result demonstrates the importance of understanding the genetic basis of fitness variation when making predictions about the microevolutionary consequences of selection.

Genetic stratification among European populations and AIM panels

There are two new papers in PLoS Genetics along with an editorial (see all below).
The papers are basically large scale studies that demonstrate the need for stratification correction among European Americans, for example in a WGA analysis of rheumatoid arthritis. They've come up with sets of AIMs (ancestry informative markers) that are useful for distinguishing between various European groups (Ashkenazi Jews, Irish, and north-south). There's lots of good stuff in these papers (beyond the scope of my post here). I wish they would have talked a bit more about what diseases differ in prevalence between European groups: Crohn's disease, rheumatoid arthritis, inflammatory bowel syndrome, celiac disease, coronary heart disease, alzheimers, multiple sclerosis, cystic fibrosis... There's lots of good figures, but these are the only figure I could manage to put here.

If you're interested in this, there are other recent papers (here, here) that have looked at European substructure and blogwise, I would also suggest Dienekes' blog, since he's really on top of this topic.

Application of Ancestry Informative Markers to Association Studies in European Americans Michael F. Seldin, Alkes L. Price

from this paper:

For example, in a recent WGA study of rheumatoid arthritis in European Americans, markers in the LCT and IRF4 genes would have been falsely implicated as associated to disease without the application of methods to control for stratification [3]. Similar empirical examples of population stratification exist for other phenotypes, and genetic risk has been reported to vary across Europe for a wide range of diseases [4–8]. In general, investigators should be alerted to consider population stratification when WGA data indicates that a particular marker shows a strong frequency gradient across Europe.

An important question is which ancestries should be evaluated in replication studies by genotyping of AIMs at additional cost. The answer to this question will vary from study to study, depending on factors such as the collection location of cases and controls, the phenotype being studied, and considerations of cost. For example, a study of a phenotype with known ancestry differences, in which cases are collected from a large city and controls are collected from throughout the country, would be well-advised to define ancestry to the fullest extent possible. On the other hand, a study of a phenotype with no known ancestry differences, involving cases and controls rigorously matched by location, might choose to bypass the use of AIMs entirely. An intermediate option would be to model only north–south ancestry, addressing the single most likely source of stratification at partial cost, with some residual risk of stratification.

Discerning the Ancestry of European Americans in Genetic Association Studies Alkes L. Price

Abstract: European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

Analysis and Application of European Genetic Substructure Using 300 K SNP Information Chao Tian et al.

Abstract: European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

Genetic genealogy...sometimes you just gotta know

Blaine Bettinger, whose blog on genetic genealogy I've been following for a while now, is running a contest to celebrate the blog's one year anniversary. He's giving away a mtDNA or Y-chromosome test from his co-sponsor DNA Heritage.
Blaine's blog is a great way to keep up with everything that's going on in the fast paced world of genetic genealogy. He covers the topic regularly from a variety of perspectives - anthropology, genomics, business, ethics, medicine...
Anyway, I'm entering this contest because I would love to get a free mtDNA test, despite some of the inherent limitations of these kinds of tests.

DNA testing for prostate cancer... to test or not to test?

For $300 you can test your DNA for your risk of developing prostate cancer. This article in the NYT describes some of the pitfalls of this kind of testing, namely that it doesn't distinguish between aggressive cancers and the more common, harmless, extremely slow growing ones. Many researchers are concerned that the costs (not just financial) of this test may outweigh the benefits... that is, until we know the genetic variants associated with the aggressiveness of the cancer.

New Genetic Risks for Prostate Cancer Identified
Gina Kolata
New York Times Jan. 16, 2008

Is there a fitness advantage to being a CFTR carrier?

This is the type of research that gets me up in the morning. Of course it's very hard to detect what they're trying to detect, but it's definitely worth a shot, and it's good to hear about "negative" results. Related to this, check out my post on a paper about a hypothesized lactose tolerance/cystic fibrosis trade-off.

CFTR mutations and reproductive outcomes in a population isolate
Irene Gallego Romero and Carole Ober
Human Genetics Volume 122, Number 6 / January, 2008

Abstract: Multiple hypotheses have been proposed to explain the high incidence of cystic fibrosis in Caucasian populations. Most rely on a fitness advantage to carriers of CF mutations, either through increased resistance to infectious disease, such as cholera, or through increased fertility. In this study we tested the latter hypothesis in the Hutterites of South Dakota, a genetic isolate with a relatively high CF carrier frequency. Following a population-wide screen for the only two mutations present in the Hutterites (M1101K, ΔF508), we tested for associations between carrier status and measures of fertility. There was no evidence of nonrandom transmission of mutations (P = 0.409) or skewed sex ratios (P = 0.847) in children of carrier parents. Moreover, carrier status was not associated with overall fertility (P = 0.597 for carrier fathers and 0.694 for carrier mothers). Although carrier males’ sibship sizes were larger than carrier females’ sibship sizes (P = 0.049), this was not significant after accounting for multiple testing. Overall, our results suggest that if there is a fertility advantage among CF carriers, it is too small to be detected in our sample (85 carriers out of ∼950 screened), or the effects are confined to ΔF508 carriers, for which there are too few in our sample to test this specific hypothesis.

Large scale whole genome sequencing in China and elsewhere

The new issue of Nature has a news story describing the projects that are to be undertaken by a Chinese institute: Beijing Genomics Institute, to sequence the entire genomes of 100 Chinese people, and then other Asians in the future; and a joint initiative by NIH and the Wellcome Trust Sanger Institute to sequence the HapMap folks and others. In addition there is the project "by a team led by George Church at Harvard University in Cambridge, Massachusetts, has begun the 'Personal Genome Project' that will examine portions of DNA from ten individuals who have agreed to share their information with the rest of the world."

I wonder what exactly this guy is referring to in this quote:

...says Rasmus Nielsen of the University of California, Berkeley. “One of the exciting things about having so many sequences from Chinese individuals is that we will be able to say how much genetic exchange there has been between continents since [early humans migrated] out of Africa. That's been very hotly debated.”

Genomics sizes up: China launches large-scale human sequencing initiative.
Jane Qiu & Erika Check Hayden
Nature 451, 234 (2008) Published online 16 January 2008

Sun, vitamin D, and cancer

their bottom line: sun exposure is worth the risks.

Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure

Johan Moan, Alina Carmen Porojnicu, Arne Dahlback, and Richard B. Setlow

PNAS January 15, 2008 vol. 105 no. 2 668-673

Abstract: Solar radiation is the main cause of skin cancers. However, it also is a main source of vitamin D for humans. Because the optimal status of vitamin D protects against internal cancers and a number of other diseases, a controversy exists: Will increased sun exposure lead to net health benefits or risks? We calculated the relative yield of vitamin D photosynthesis as a function of latitude with a radiative transfer model and cylinder geometry for the human skin surface. The annual yield of vitamin D is 3.4 and 4.8 times larger below the equator than in the U.K. and Scandinavia, respectively. In populations with similar skin types, there are clear latitude gradients of all major forms of skin cancer, indicating a north–south gradient in real sun exposure. Surprisingly, the incidence rates of major internal cancers also increase from north to south. However, the survival prognosis also improves significantly from north to south. Reasons for these findings are discussed in view of the role of vitamin D. In Norway, melanoma rates increased by a factor of 6 from 1960 to 1990, while the prognosis improved in the same period. After 1990, melanoma rates have remained constant or even decreased in age groups less than 50 years, whereas the prognosis has not improved further. These data, together with those for internal cancers and the beneficial effects of an optimal vitamin D status, indicate that increased sun exposure may lead to improved cancer prognosis and, possibly, give more positive than adverse health effects.

K9 genetics - what can we learn?

This paper is a good review of dog genetics, and discusses the potential that dogs have for understanding the genetics of behavioral traits. P-ter at GNXP has also covered this topic pretty extensively. Here, here, here are some of my previous posts on various aspects of dog genetics.
Some interesting facts from this paper:

• "dogs were domesticated 15,000 to 40,000 years before present"
• on the farm fox experiment: "despite rigorous selection based solely on behavior, several morphologic traits that typically distinguish domestic dogs from their wild progenitors began to appear in the foxes,19, 20 including widened skulls, shortened snouts, floppy ears, shortened tails, curly tails, and altered coat color patterns. In aggregate, these data suggest a link between selection for behavior and generation of a subset of morphological traits observed in modern domestic dogs.'"
• the candidate gene approach has not worked in dogs, perhaps due to small samples.
• LD in dogs is much larger (almost 10 times longer) than it is in humans
  

Behavioral stuff is fine, but how about disease related traits? Many dogs are now developing diabetes (thanks to us, I assume), and some breeds are at a greater risk of developing diabetes than others . The Samoyed (pictured above) is one of them.

Canine Behavioral Genetics: Pointing Out the Phenotypes and Herding up the Genes

Tyrone C. Spady and Elaine A. Ostrander

The American Journal of Human Genetics (2008) Volume 82, Issue 1, 10-18

Abstract: An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, tracking, hunting, and so forth are likely to be controlled, at least in part, at the genetic level. Recent studies in canine genetics suggest that small numbers of genes control major morphologic phenotypes. By extension, we hypothesize that at least some canine behaviors will also be controlled by small numbers of genes that can be readily mapped. In this review, we describe our current understanding of a representative subset of canine behaviors, as well as approaches for phenotyping, genome-wide scans, and data analysis. Finally, we discuss the applicability of studies of canine behavior to human genetics.

ACTN3 knockout mice become marathon runners

Kudos to Razib at GNXP on beating me to this new paper in Human Molecular Genetics. I've also talked about many reports on this gene (see here, here for latest) and about another paper that found a similar effect for marathon mice (they can run for five hours without stopping), but linked to another gene: PPAR-delta (here, and here).

Autosomal data from Polynesians: Asian or Melanesian origin?

This paper highlights the differences between what mtDNA, Y-chromosome and autosomal data tell us about population genetics. Here's a related post from Dienekes about the so-called "slow boat model".

Genome-wide Analysis Indicates More Asian than Melanesian Ancestry of Polynesians.

Kayser M, Lao O, Saar K, Brauer S, Wang X, Nürnberg P, Trent RJ, Stoneking M.

American Journal of Human Genetics 2008 Jan;82(1):194-8.

Abstract: Analyses of mitochondrial DNA (mtDNA) and nonrecombining Y chromosome (NRY) variation in the same populations are sometimes concordant but sometimes discordant. Perhaps the most dramatic example known of the latter concerns Polynesians, in which about 94% of Polynesian mtDNAs are of East Asian origin, while about 66% of Polynesian Y chromosomes are of Melanesian origin. Here we analyze on a genome-wide scale, to our knowledge for the first time, the origins of the autosomal gene pool of Polynesians by screening 377 autosomal short tandem repeat (STR) loci in 47 Pacific Islanders and compare the results with those obtained from 44 Chinese and 24 individuals from Papua New Guinea. Our data indicate that on average about 79% of the Polynesian autosomal gene pool is of East Asian origin and 21% is of Melanesian origin. The genetic data thus suggest a dual origin of Polynesians with a high East Asian but also considerable Melanesian component, reflecting sex-biased admixture in Polynesian history in agreement with the Slow Boat model. More generally, these results also demonstrate that conclusions based solely on uniparental markers, which are frequently used in population history studies, may not accurately reflect the history of the autosomal gene pool of a population.

DRD4 and inter-racial mating

An allele in the DRD4 gene has previously been found to be associated with ADHD, novelty seeking behavior, migratory behavior, and exhibits marked population differences (Harpending and Cochran wrote an important paper called "In our genes" on this a few years ago in PNAS). People have also looked at its effect on reproductive behavior and personality in birds.
I'm surprised by what they did in the paper below. First they looked at timing of reproductive behavior. Then they looked at whether people with this 7R allele had more multiracial ancestries!! I did not look at what their reasoning for this was, but it probably goes something like this. Those with the 7R allele are more prone to novelty seeking and migratory behavior, therefore more likely to out-marry? It seems there would be several confounders here, but maybe they considered those. These results regarding multi-racial ancestry and the 7R allele are very surprising to me.

Polymorphisms in the dopamine D4 and D2 receptor genes and reproductive and sexual behaviors.

Eisenberg, D.T.A., Campbell, B., MacKillop, J., Modi, M., Dang, D., Lum, J.K., and Wilson, D.S. .

Evolutionary Psychology, (2007) 5(4): 696-715.

Abstract: Human reproductive and sexual behaviors are heritable and may represent
integral life history traits that are likely partially subserved by the dopamine system. Two
dopamine receptor polymorphisms, DRD4 48bp VNTR and DRD2 TaqI A, were examined
in relation to the Sexual-Orientation Inventory (SOI), age at first sexual intercourse, desired
age of marriage, and desired age to have children in 195 (45% male) individuals from a
general student population. As DRD4 7R alleles have been associated with migratory
behavior, we also examined whether those with more 7R alleles had a greater frequency of
multi-racial ancestries. Minor alleles of both polymorphisms (7R and A1 respectively) are
believed to decrease the function of their respective receptors. Individuals with DRD4 7R
alleles were more likely to have had sexual intercourse and to desire children earlier in life. In addition, DRD4 7R+ individuals were more likely to report multi-racial ancestries.Individuals with DRD2 A1 alleles were more likely to not want children and not want to marry. These results suggest that polymorphisms in the DRD4 and DRD2 genes are meaningfully associated with variation in reproductive and sexual behaviors. These results are provisionally interpreted as consistent with other findings suggesting that DRD4 7R and DRD2 A1 alleles are adaptive for lower offspring investment strategies in dynamic social environments.

Do students of evolutionary biology appreciate the importance of random processes?

I've been teaching introductory human evolution type courses for three years now, so I found this paper in PLoS Biology pretty interesting. Basically, what they find is that student who are learning molecular biology and evolutionary biology have a hard time grasping the concept of randomness. Since I give a lot of short answer questions on my student's tests, I have some insight into how students think, and I agree with what they find. I've found that students tend to think that there's some intention or purpose that underlies evolutionary change... that organisms are actively moving to some goal. I like how they explain it in the excerpts I've put below.

Recognizing Student Misconceptions through Ed's Tools and the Biology Concept Inventory

Michael W. Klymkowsky*, Kathy Garvin-Doxas

PLoS Biology 6(1): e3

here is what they find with respect to how students under-appreciate the importance of random processes:

"A common observation, which echoes the finding of Lecoutre et al., was that students were unwilling to see random processes as capable of directed effect in themselves—they routinely seek alternative rational explanations, the dominant one being the presumption of drivers that are actually responsible for the observed effects. In the absence of these drivers, for example, concentration gradients with respect to diffusion or active selection with respect to changes in allele frequency, the macroscopic behavior stops. The concept of random processes giving rise to emergent behavior is almost totally absent from their (explicit) thought processes.

...Given that much of evolutionary change is ultimately driven by, or is the result of, random processes rather than selection acting alone (see [5] and references therein), and given the apparent tendency of students to reject or overlook random events as the cause of emergent behaviors, what emerges is “neo-vitalist” mindset that presumes the presence of directed processes and imposes a level of meaning on the system (and its components) that may well not be present. Not all genetic changes have an immediate adaptive significance, and not all molecular processes are actively directed. Does this view interfere with understanding? The answer must be yes—since it leads one to assign purpose to a process (be it evolution or osmosis), and ignores what can be achieved at the underlying molecular level. From an evolutionary perspective, it leads to “just-so” stories that project meaning onto every variation, whether meaningful or not, and obscures the basic mechanisms that make evolutionary theory so valuable. On the molecular biology level it leads to anthropomorphic explanations of molecular interactions, some of which even imply action at a distance; e.g., ATP synthase molecules “seek out and grab” ADP molecules [25]."

and then, there's some discussion about what can be done to circumvent this problem:

"What, if anything, can be done to improve understanding of the role of random processes in particular, and emergent behaviors in general? Here are some hints. From the perspective of course and curriculum content, we need to provide students with opportunities to work with random systems, and explicitly state (and confront) their assumptions. One approach is through direct experimentation and accessible simulations that focus on the concept of randomness in specific processes. Under these conditions, events like allele loss from a population can be viewed as either the result of selection or genetic drift (or both)—leading to an understanding of the effects of population size on evolutionary effects. In the context of cell biology, students need to directly and explicitly consider the efficacy of diffusion in cellular and organismic context—why is it (apparently) adequate within a bacterial cell, but inadequate for a neuron? For a particular context, one might require students to predict, explaining their thinking, when a process is likely to be active (energy requiring) or passive (diffusive). How can the diffusive properties of a molecule be regulated by intracellular/extracellular structures and molecular interactions? For example, one could ask in which developmental or organismic contexts we can expect diffusion to be adequate (consider [4]). The development of experimental scenarios and/or computer-based simulations can then be used to test and re-evaluate students' assumptions."

Thrifty-gene hypothesis tested...brilliantly!

This is one of the best papers I've read in a while, not so much for the details of what they did, because I couldn't really follow all the economic jargon and models, but more for the overall concept. Every time I go to a buffet, all-you-can-eat style place (which is not often) I fantasize about doing research looking at optimal foraging theory in humans. I would want to see which people go for what foods (fat, protein, carbohydrates, vegetables, fruits, meat). I thought it would be fascinating to see what SES, biological, genetic, cultural factors determine how people decide on which foods to eat, or what they put place value on. I know that for me, for example, I find that my money would travel farthest if I take advantage of all the meat there is, but this can be seen as a very short term strategy, and probably the most optimal foraging strategy is to go for all the vegetables and fruit and "healthy stuff", even though I'd feel like I was "wasting" my money.
In this paper, the authors looked at purchases at nine grocery stores that are mainly frequented by Native Americans and nine grocery stores that are mainly frequented by Whites (or maybe just non-Native Americans) and looked at differences in purchasing behavior between them. They find that Native Americans do place a higher "dynamic shadow price" on protein, lending some support to the thrifty gene hypothesis. Now, I'm not saying this is water tight evidence or that there aren't issues with their analyses (or that I even understand everything they did), but I think their overall method is awesome.

Native American Obesity: An Economic Model of the "Thrifty Gene" Theory

Timothy J. Richards, Paul M. Patterson

American Journal of Agricultural Economics, August 2006, 88 (3), 542–560.

Abstract: Native American obesity is hypothesized to result from three potential causes: (1) a genetic predisposition, or the "thrifty gene," (2) a rational addiction to nutrients, and (3) dietary adjustment costs. These hypotheses are tested using a two-stage household production approach and scanner data from a panel of Native and non-Native supermarkets. Nutrient intake for both groups is strongly influenced by adjustment costs. Native Americans tend to place higher implicit valuations on protein relative to fats and carbohydrates compared to non-Natives. Consequently, reductions in real carbohydrate prices over time may be a cause of high incidence of Native American obesity.

Genetic structure among Mexican-Mestizo and Amerindian males

They examine the Y-chromosome among 314 Mexican male students at the Universidad de Guadalajara and 108 Amerindian males. They also compare their findings to published data on various other populations (other Amerindian populations and Spanish).
They do some interesting analyses relating genetic admixture to geography and population structure among the various pre-Hispanic Amerindian groups.

Genetic admixture, relatedness, and structure patterns among Mexican populations revealed by the Y-chromosome

H. Rangel-Villalobos, J.F. Muñoz-Valle, A. González-Martín, A. Gorostiza, M.T. Magaña, L.A. Páez-Riberos

American Journal of Physical Anthropology, Early view

Abstract: Y-linked markers are suitable loci to analyze genetic diversity of human populations, offering knowledge of medical, forensic, and anthropological interest. In a population sample of 206 Mestizo males from western Mexico, we analyzed two binary loci (M3 and YAP) and six Y-STRs, adding to the analysis data of Mexican Mestizos and Amerindians, and relevant worldwide populations. The paternal ancestry estimated in western Mexican-Mestizos was mainly European (60-64%), followed by Amerindian (25-21%), and African (15%). Significant genetic heterogeneity was established between Mestizos from western (Jalisco State) and northern Mexico (Chihuahua State) compared with Mexicans from the center of the Mexican Republic (Mexico City), this attributable to higher European ancestry in western and northern than in central and southeast populations, where higher Amerindian ancestry was inferred. This genetic structure has important implications for medical and forensic purposes. Two different Pre-Hispanic evolutionary processes were evident. In Mesoamerican region, populations presented higher migration rate (Nm = 24.76), promoting genetic homogeneity. Conversely, isolated groups from the mountains and canyons of the Western and Northern Sierra Madre (Huichols and Tarahumaras, respectively) presented a lower migration rate (Nm = 10.27) and stronger genetic differentiation processes (founder effect and/or genetic drift), constituting a Pre-Hispanic population substructure. Additionally, Tarahumaras presented a higher frequency of Y-chromosomes without Q3 that was explained by paternal European admixture (15%) and, more interestingly, by a distinctive Native-American ancestry. In Purepechas, a special admixture process involving preferential integration of non-Purepecha women in their communities could explain contrary genetic evidences (autosomal vs. Y-chromosome) for this tribe.