Saturday, March 31, 2007

Spencer Wells interview

The newest issue of PLoS Genetics has an interview with Spencer Wells, the author of Journey of Man (book and documentary) who is now working for National Geographic on the Genographic project.

His PhD advisor at Harvard was Richard Lewontin (the 15% guy). It was interesting to see how he made connections throughout his career that gave him access to various research resources. This story about when he first arrived in central Asia to collect samples is pretty funny:

"When we got off the plane, Ruslan picked us up with other members of the Institute. We went to his office—it was 8 o'clock in the morning—he gave us shots of vodka and said, “We have two variants: first variant is we rest today and work tomorrow, and the second variant is work today.""

about the people in Tajikistan
"These people can do it back six, seven, eight generations. They've always lived in the same place and beyond that they know even more about their history, but not necessarily their names...So they have a sense, a clear idea of where they came from, that something is passed from generation that ties them to their ancestors"

Apparently, the Genographic project has a center devoted to ancient DNA

Also, they've had 165,00o people who "sent in their 100 bucks and their cheek swab [for DNA analysis]" -- surprisingly high number. I wonder who these people are and why they do it?

Population differences in adipocytokines and the potential of admixture mapping

Genetic admixture, adipocytokines, and adiposity in Black Americans: the Health, Aging, and Body Composition study.

Wassel Fyr CL, Kanaya AM, Cummings SR, Reich D, Hsueh WC, Reiner AP, Harris TB, Moffett S, Li R, Ding J, Miljkovic-Gacic I, Ziv E; for the Health, Aging, Body Composition Study.

Hum Genet. 2007 Mar 28; [Epub ahead of print]

Abstract: Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3 +/- 15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-alpha SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin.

Thursday, March 29, 2007

Another one on signatures of selection, but for fixed alleles

New paper on evidence from HapMap SNPs on population specific selective sweeps...(via p-ter at GNXP).Unlike other tests of selection, their test looks for alleles that have reached fixation. They find evidence for selection sweeps for pigmentation genes, earwax type related genes, malaria resistance, skeletal development, fertility related genes (they always seem to find signatures of selection for reproduction related genes, for some reason??)

A Practical Genome Scan for Population-Specific Strong Selective Sweeps That Have Reached Fixation

Ryosuke Kimura, Akihiro Fujimoto, Katsushi Tokunaga, Jun Ohashi

PLoS ONE 2(3): e286

Abstract: Phenotypic divergences between modern human populations have developed as a result of genetic adaptation to local environments over the past 100,000 years. To identify genes involved in population-specific phenotypes, it is necessary to detect signatures of recent positive selection in the human genome. Although detection of elongated linkage disequilibrium (LD) has been a powerful tool in the field of evolutionary genetics, current LD-based approaches are not applicable to already fixed loci. Here, we report a method of scanning for population-specific strong selective sweeps that have reached fixation. In this method, genome-wide SNP data is used to analyze differences in the haplotype frequency, nucleotide diversity, and LD between populations, using the ratio of haplotype homozygosity between populations. To estimate the detection power of the statistics used in this study, we performed computer simulations and found that these tests are relatively robust against the density of typed SNPs and demographic parameters if the advantageous allele has reached fixation. Therefore, we could determine the threshold for maintaining high detection power, regardless of SNP density and demographic history. When this method was applied to the HapMap data, it was able to identify the candidates of population-specific strong selective sweeps more efficiently than the outlier approach that depends on the empirical distribution. This study, confirming strong positive selection on genes previously reported to be associated with specific phenotypes, also identifies other candidates that are likely to contribute to phenotypic differences between human populations.

Calorie restriction and mitochondrial function

does calorie restriction extend lifespan in humans? we don't know for sure yet, but it looks like it might increase mitochondrial function in muscle (over 6 months).

Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans

Anthony E. Civitarese*, Stacy Carling, Leonie K. Heilbronn, Mathew H. Hulver, Barbara Ukropcova, Walter A. Deutsch, Steven R. Smith, Eric Ravussin for the CALERIE Pennington Team

PLoS Med 4(3): e76

Background Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.

Methods and Findings The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 ± 1.0 y), overweight (body mass index, 27.8 ± 0.7 kg/m2) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, −135 ± 42 kcal/d, p = 0.002 and CREX, −117 ± 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < p =" 0.005)" p =" 0.003)" p =" 0.011)," style="font-weight: bold;">
Conclusions The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults.

Wednesday, March 28, 2007

More on Neanderthal genetics

check out this commentary piece in the journal Heredity- nothing really new- just discusses how ancient DNA has shined some light on Neanderthal divergence time, effective population size and admixture:

Ancient DNA closes on human uniqueness: The base nature of Neanderthals

R A Foley and M Mirazón Lahr

Heredity (2007) 98, 187–188

Tuesday, March 27, 2007

Genetics of Neanderthals vs. Modern Humans

Thomas C. Erren, Paul Cullen, Michael Erren;, Edward M. Rubin, and James P. Noonan
Science 23 March 2007: 1664.
I didn't put a link to this letter and reply because there is no abstract. The first letter is from someone who thinks that we should start by looking at specific regions in the neanderthal genome as opposed to the whole genome (areas related to fat metabolism - why fat metabolism? I don't know - someone please explain why this would be interesting when comparing neanderthals and moderns...I can see for comparing humans and other apes ...
Noonan argues in response that we should first start by looking at the whole genome, then focus in on areas that look promising.
This raises a lot of issues as to what we expect the differences between neanderthals and humans to be, how well we know the genetics of these traits, and of course cost-efficiency issues.
by the way, there's a pretty funny quote at the end of the first letter.

Monday, March 26, 2007

Monday Map - Population growth

Thinking about signatures of recent selection, here's some maps from Worldmapper that show population in year 1, year 1500, year 1900, year 1960 (in order, as you scroll down). I was interested where and when human populations grew the most. First here's a graph showing human population growth on a larger time scale:

Sunday, March 25, 2007

Mortality rates among hunter-gatherers

Here's research from some local folks... the point: mortality rates were possibly pretty high for most of human evolution until recently...but still considerably lower across the lifespan than chimps...I assume. They specifically point out conspecific violence in this Hiwi group.

High adult mortality among Hiwi hunter-gatherers: Implications for human evolution

Kim Hill, A.M. Hurtado and R.S. Walker

Journal of Human Evolution Volume 52, Issue 4 , April 2007, Pages 443-454

Abstract: Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies.

Tuesday, March 20, 2007

North African early H. sapiens

this one is open access...unfortunately don't have time to look at it

Earliest evidence of modern human life history in North African early Homo sapiens

Tanya M. Smith, Paul Tafforeau , Donald J. Reid, Rainer Grün, Stephen Eggins, Mohamed Boutakiout, and Jean-Jacques Hublin

PNAS online before print

Abstract: Recent developmental studies demonstrate that early fossil hominins possessed shorter growth periods than living humans, implying disparate life histories. Analyses of incremental features in teeth provide an accurate means of assessing the age at death of developing dentitions, facilitating direct comparisons with fossil and modern humans. It is currently unknown when and where the prolonged modern human developmental condition originated. Here, an application of x-ray synchrotron microtomography reveals that an early Homo sapiens juvenile from Morocco dated at 160,000 years before present displays an equivalent degree of tooth development to modern European children at the same age. Crown formation times in the juvenile's macrodont dentition are higher than modern human mean values, whereas root development is accelerated relative to modern humans but is less than living apes and some fossil hominins. The juvenile from Jebel Irhoud is currently the oldest-known member of Homo with a developmental pattern (degree of eruption, developmental stage, and crown formation time) that is more similar to modern H. sapiens than to earlier members of Homo. This study also underscores the continuing importance of North Africa for understanding the origins of human anatomical and behavioral modernity. Corresponding biological and cultural changes may have appeared relatively late in the course of human evolution.

Saturday, March 17, 2007

MATP and skin color variation

It looks like they have anintersting and large sample and they're looking at relationships between polymoprhisms and phenotype.

Promoter polymorphisms in the MATP (SLC45A2) gene are associated with normal human skin color variation.

Graf J, Voisey J, Hughes I, van Daal A.

Hum Mutat. 2007 Mar 14; [Epub ahead of print]

Abstract: Human pigmentation is a complex physical trait in which the membrane-associated transporter protein (MATP) plays an important role as it is involved in intracellular processing and trafficking of melanosomal proteins. Recently, pathogenic mutations in MATP have been shown to cause oculocutaneous albinism type 4, while other polymorphisms are known to have a role in normal pigmentation variation. We previously reported significant associations of two coding region polymorphisms with hair, skin, and eye color in Caucasians. Here we characterize the promoter region of MATP identifying two new transcription start sites and a novel duplication (c.-1176_-1174dupAAT). A total of 700 individuals from five different population groups (529 Caucasians, 38 Asians, 46 African Americans, 47 Australian Aborigines, and 40 Spanish Basques) were genotyped for known promoter polymorphisms c.-1721C>G (rs13289) and c.-1169G>A (rs6867641), as well as c.-1176_-1174dupAAT. Allele frequencies of all three polymorphisms were significantly different between population groups. In Caucasians, the -1721G, +dup, and -1169A alleles were significantly associated with olive skin color. The three promoter polymorphisms were found to be in linkage disequilibrium with each other but not with the two previously reported coding region polymorphisms. Functional analyses in a melanoma cell line showed that the promoter haplotype -1721G, +dup, -1169A significantly decreased MATP transcription. This report provides further evidence for the involvement of MATP in normal pigmentation variation by identifying associations between MATP alleles and skin color variation in Caucasians and demonstrating a functional significance of these polymorphisms.

Lipid profiles in African Americans

From the abstract: "These observed associations between African ancestry and several lipid traits are consistent with the general tendency of individuals of African descent to have healthier lipid profiles compared to European-Americans. There was no association between genetic ancestry and hypertension, BMI, waist circumference, CRP level, or coronary artery calcification."

Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study.

Reiner AP, Carlson CS, Ziv E, Iribarren C, Jaquish CE, Nickerson DA.

Hum Genet. 2007 Mar 14; [Epub ahead of print]

Abstract: African-American populations are genetically admixed. Studies performed among unrelated individuals from ethnically admixed populations may be both vulnerable to confounding by population stratification, but offer an opportunity for efficiently mapping complex traits through admixture linkage disequilibrium. By typing 42 ancestry-informative markers and estimating genetic ancestry, we assessed genetic admixture and heterogeneity among African-American participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We also assessed associations between individual genetic ancestry and several quantitative and binary traits related to cardiovascular risk. We found evidence of population sub-structure and excess inter-marker linkage disequilibrium, consistent with recent admixture. The estimated group admixture proportions were 78.1% African and 22.9% European, but differed according to geographic region. In multiple regression models, African ancestry was significantly associated with decreased total cholesterol, decreased LDL-cholesterol, and decreased triglycerides, and also with increased risk of insulin resistance. These observed associations between African ancestry and several lipid traits are consistent with the general tendency of individuals of African descent to have healthier lipid profiles compared to European-Americans. There was no association between genetic ancestry and hypertension, BMI, waist circumference, CRP level, or coronary artery calcification. These results demonstrate the potential for confounding of genetic associations with some cardiovascular disease-related traits in large studies involving US African-Americans.

Chimp paternity mystery solved

This is like the chimpanzee version of the Anna Nicole Smith paternity mystery:

From Yahoo!: Chimp DNA test says Conan's the daddy

All the male chimps in that group had received vasectomies. From the stoty:"But its attending veterinarian, Elysse Orchard, ... said that vasectomy failures in chimpanzees are not uncommon."

Conan was the lucky one.

Thursday, March 15, 2007

Ancient pig DNA !!

...enough said...

Phylogeny and ancient DNA of Sus provides insights into neolithic expansion in Island Southeast Asia and Oceania

Greger Larson, Thomas Cucchi, Masakatsu Fujita, Elizabeth Matisoo-Smith, etc...

PNAS, Published online before print March 14, 2007

Abstract: Human settlement of Oceania marked the culmination of a global colonization process that began when humans first left Africa at least 90,000 years ago. The precise origins and dispersal routes of the Austronesian peoples and the associated Lapita culture remain contentious, and numerous disparate models of dispersal (based primarily on linguistic, genetic, and archeological data) have been proposed. Here, through the use of mtDNA from 781 modern and ancient Sus specimens, we provide evidence for an early human-mediated translocation of the Sulawesi warty pig (Sus celebensis) to Flores and Timor and two later separate human-mediated dispersals of domestic pig (Sus scrofa) through Island Southeast Asia into Oceania. Of the later dispersal routes, one is unequivocally associated with the Neolithic (Lapita) and later Polynesian migrations and links modern and archeological Javan, Sumatran, Wallacean, and Oceanic pigs with mainland Southeast Asian S. scrofa. Archeological and genetic evidence shows these pigs were certainly introduced to islands east of the Wallace Line, including New Guinea, and that so-called "wild" pigs within this region are most likely feral descendants of domestic pigs introduced by early agriculturalists. The other later pig dispersal links mainland East Asian pigs to western Micronesia, Taiwan, and the Philippines. These results provide important data with which to test current models for human dispersal in the region.

Wednesday, March 14, 2007

Four Stone Hearth Anthropology Blog Carnival

Check out the latest issue of the Four Stone Hearth. I was particulary intrigued by this submission about a Native American paramiltary group that is being used by the US military to track down Al-Qaeda in Afghanistan.

Ascertainment bias at ADLH2 in Japanese population

Ascertainment Bias and the Pattern of Nucleotide Diversity at the Human ALDH2 Locus in a Japanese Population

Benjamin T. Brown, August Woerner and Jason A. Wilder

Journal of Molecular Evolution v. 64, March 2007; 375-385

Abstract: Many East Asian human populations harbor a high-frequency deficiency allele for the aldehyde dehydrogenase 2 (ALDH2) enzyme, a critical protein involved in the metabolism of ethanol. Here we use resequencing and long-range SNP haplotype data from a Japanese sample to test whether patterns of nucleotide diversity and linkage disequilibrium at this locus are compatible with a standard neutral model of evolution. Examination of the pattern of polymorphism at a locus such as this, where the frequency of a common allele is known a priori, introduces an ascertainment bias that must be corrected for in analyses of the frequency spectrum of polymorphisms. We apply a flexible and generally applicable simulation approach to correct for this bias in our ALDH2 data and, also, to explore the effect of bias on the commonly used summary statistics Tajima’s D, Fu and Li’s D, and Fay and Wu’s H. Our study finds no evidence that the pattern of genetic variation at ALDH2 differs from that expected under a standard neutral model. However, our general examination of ascertainment bias indicates that a priori knowledge of segregating alleles greatly affects the expected distributions of summary statistics. Under many parameter combinations we find that ascertainment bias introduces an elevated rate of false positives when summary statistics are used to test for deviations from a standard neutral model. However, we also show that over a wide range of conditions the power of all summary statistics can be greatly increased by incorporating prior knowledge of segregating alleles.

Monday, March 12, 2007

Monday Map - Homo Erectus finds in Eurasia

For my own selfish research and teaching purposes, this week's map is of Homo erectus finds in Eurasia from this website. Any comments on its accuracy are more than welcome.

Saturday, March 10, 2007

"Genetic Similarities Within and Between Human Populations"

How often am I genetically more similar to a person of a different group compared to being more similar to someone of my own group? This paper (see abstract below) discusses this question in the light of several recent studies. They single out a recent paper by Bamshad (2004, NRG) in which he "showed, using multi-locus statistics and nearly 400 polymorphic loci, that pairs of individuals are more often similar than pairs from the same population."
The authors also bring up the point that in the Rosenberg (2002, Science) data set of 340 or so microsatellites typed in the CEPH panel: "Europeans proved to be more similar to Asians than to other Europeans 38% of the time." This was quite surprising to me.
From their conclusion:

"Thus the answer to the question "How often is a pair of individuals from one population genetically more dissimilar than two individuals chosen from two different populations?" depends on the number of polymorphisms used to define that dissimilarity and the populations being compared... Given ten loci and three distinct populations, the answer is w=0.3, or nearly one-third of the time. With 100 loci, the answer is about 20% of the time; and even using 1,000 loci, w=10%. However, if genetic similarity is measured over many thousands of loci, the answer becomes "never" when individuals are sampled from geographically separated populations."

They then ask:

"How can the observations of accurate classifiability be reconciled with high between-population similarities among individuals."

and go on to discuss the crucial reliance on "aggregate properties of populations".

They go on to discuss the implications of the complex disease phenotype - genotype - group membership relationships.

Then in their final paragraph:

"The fact that, given enough genetic data. individuals can be correctly assigned to their population of origin is compatible with the observation that most human genetic variation is found within populations, not between them. It is also compatible with our finding that, even when the most distinct populations are considered and hundreds of loci are used, individuals are frequently more similar to members of other populations than to their own population. Thus caution should be used when using geographic or genetic ancestry to make inferences about individual phenotypes."

I wish I could have read this paper more closely but am somewhat time crunched, and it's not in published pdf format yet, which makes it unpleasant to read (figures at the end of the text, etc..)

Genetic Similarities Within and Between Human Populations

David J Witherspoon , Stephen Wooding , Alan R Rogers, Elizabeth E Marchani W Scott Watkin, Mark A Batzer and Lynn B Jorde

Genetics. Published Articles Ahead of Print: March 4, 2007

Abstract: The proportion of human genetic variation due to differences between populations is modest, and individuals from different populations can be genetically more similar than individuals from the same population. Yet sufficient genetic data can permit accurate classification of individuals into populations. To resolve this apparent conflict, we analyzed the question "How often is a pair of random individuals from two different populations genetically more similar than a pair of individuals randomly selected from any single population"; We compared this frequency (w) with error rates for classification methods, using data sets that vary in number of loci, diversity of populations, and polymorphism ascertainment strategies. Classification methods achieve higher discriminatory power than the individual-based measure, w, because of their use of aggregate properties of populations. The number of loci analyzed is the most critical variable: with one hundred polymorphisms, accurate classification is possible, but w remains sizable, even when using populations as distinct as sub-Saharan Africans and Europeans. Phenotypes controlled by a dozen or fewer loci can be expected to show substantial overlap between human populations. This provides empirical justification for caution when using population labels in biomedical settings, with broad implications for personalized medicine, pharmacogenetics, and the meaning of race.

Thursday, March 08, 2007

Mapping CNVs with SNPs

From what I can understand from the abstract: a way to get at copy number variation from SNP data...sounds pretty cool.

QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data.

Colella S, Yau C, Taylor JM, Mirza G, Butler H, Clouston P, Bassett AS, Seller A, Holmes CC, Ragoussis J.

Nucleic Acids Res. 2007 Mar 6; [Epub ahead of print]

Array-based technologies have been used to detect chromosomal copy number changes (aneuploidies) in the human genome. Recent studies identified numerous copy number variants (CNV) and some are common polymorphisms that may contribute to disease susceptibility. We developed, and experimentally validated, a novel computational framework (QuantiSNP) for detecting regions of copy number variation from BeadArraytrade mark SNP genotyping data using an Objective Bayes Hidden-Markov Model (OB-HMM). Objective Bayes measures are used to set certain hyperparameters in the priors using a novel re-sampling framework to calibrate the model to a fixed Type I (false positive) error rate. Other parameters are set via maximum marginal likelihood to prior training data of known structure. QuantiSNP provides probabilistic quantification of state classifications and significantly improves the accuracy of segmental aneuploidy identification and mapping, relative to existing analytical tools (Beadstudio, Illumina), as demonstrated by validation of breakpoint boundaries. QuantiSNP identified both novel and validated CNVs. QuantiSNP was developed using BeadArraytrade mark SNP data but it can be adapted to other platforms and we believe that the OB-HMM framework has widespread applicability in genomic research. In conclusion, QuantiSNP is a novel algorithm for high-resolution CNV/aneuploidy detection with application to clinical genetics, cancer and disease association studies.

Why it pays to be picky

in case there was any doubt, mate preferences do matter...Gotta love model organisms. It would be interesting to somehow show that optional mate preference is different for each individual.

Experimental constraints on mate preferences in Drosophila pseudoobscura decrease offspring viability and fitness of mated pairs

Wyatt W. Anderson , Yong-Kyu Kim, and Patricia Adair Gowaty

PNAS Early Edition

Abstract: Using Drosophila pseudoobscura, we tested the hypothesis that social constraints on the free expression of mate preferences, by both females and males, decrease offspring viability and reproductive success of mating pairs. Mate preference arenas eliminated intrasexual combat and intersexual coercion. The time female and male choosers spent in arena tests near either of two opposite-sex individuals measured the preferences of choosers. We placed choosers in breeding trials with their preferred or nonpreferred discriminatee when they met the minimum criteria for showing the same preference in two consecutive tests. There was no statistically significant difference in the frequency of female and male choosers meeting minimal preference criteria. There was a significant difference between female and male choosers for offspring viability, with female choice having the greater effect, but there was not a significant difference in the overall reproductive success of male and female choosers. There were significant differences in fitness between matings to preferred and nonpreferred partners. Female and male choosers paired with their nonpreferred discriminatees had offspring of significantly lower viability, as predicted by the constraints hypothesis. Reproductive success, our measure of overall fitness, was greater when males or females mated with the partner they preferred rather than the one they did not prefer.

Wednesday, March 07, 2007

Lek paradox, male secondary-sexual traits, and maternal influences

A potential resolution to the lek paradox through indirect genetic effects

Christine W. Miller AFF1 and Allen J. Moore

Proceedings of the Royal Society B: Biological Sciences: First Cite Early Online

Females often prefer males with elaborate traits, even when they receive no direct benefits from their choice. In such situations, mate discrimination presumably has genetic advantages; selective females will produce offspring of higher genetic quality. Over time, persistent female preferences for elaborate secondary-sexual traits in males should erode genetic variance in these traits, eventually eliminating any benefit to the preferences. Yet, strong female preferences persist in many taxa. This puzzle is called the lek paradox and raises two primary questions: do females obtain genetic benefits for offspring by selecting males with elaborate secondary-sexual characteristics and, if so, how is the genetic variation in these male traits maintained? We suggest that indirect genetic effects may help to resolve the lek paradox. Maternal phenotypes, such as habitat selection behaviours and offspring provisioning, often influence the condition and the expression of secondary-sexual traits in sons. These maternal influences are commonly genetic based (i.e. they are indirect genetic effects). Females choosing mates with elaborate traits may receive ‘good genes’ for daughters in the form of effective maternal characteristics. Recognizing the significance of indirect genetic effects may be important to our understanding of the process and consequences of sexual selection.

Monday, March 05, 2007

Brits, Irish, what's the difference?

Nicholas Wade has a story in the New York Times about how the British and the Irish are genetically more similar than people would have been led to believe. The story revolves around a new book by geneticist Stephen Oppenheimer called "The Origins of the British: A Genetic Detective Story" (Carroll & Graf, 2006). This story is very reminiscent of a study done three or four years ago about how Israelis and Palestinians were virtually genetically indistinguishable, much to each group's consternation, I'm sure. Here are some of the more interesting parts, and my Jerry Springer-esque final thought at the end:

"Historians teach that they are mostly descended from different peoples: the Irish from the Celts and the English from the Anglo-Saxons who invaded from northern Europe and drove the Celts to the country’s western and northern fringes."

"Stephen Oppenheimer, a medical geneticist at the University of Oxford, says the historians’ account is wrong in almost every detail. In Dr. Oppenheimer’s reconstruction of events, the principal ancestors of today’s British and Irish populations arrived from Spain about 16,000 years ago, speaking a language related to Basque."

"The British Isles were unpopulated then, wiped clean of people by glaciers that had smothered northern Europe for about 4,000 years and forced the former inhabitants into southern refuges in Spain and Italy. When the climate warmed and the glaciers retreated, people moved back north. The new arrivals in the British Isles would have found an empty territory, which they could have reached just by walking along the Atlantic coastline, since the English Channel and the Irish Sea were still land."

"A different view of the Anglo-Saxon invasions has been developed by Mark Thomas of University College, London. Dr. Thomas and colleagues say the invaders wiped out substantial numbers of the indigenous population, replacing 50 percent to 100 percent of those in central England. Their argument is that the Y chromosomes of English men seem identical to those of people in Norway and the Friesland area of the Netherlands, two regions from which the invaders may have originated."

"Dr. Oppenheimer disputes this, saying the similarity between the English and northern European Y chromosomes arises because both regions were repopulated by people from the Iberian refuges after the glaciers retreated."

I never knew that the Irish identified themselves so fiercely as being different from the British. It illustrates once again, how in humans, the notion of blood ties are so closely linked to group affiliation, and also very importantly - vice versa.

Caucasians, Asians, eye color and melatonin

I have no idea what's going on here (didn't read paper), but I thought I would post the abstract, in case anyone knows and would like to explain.

Influence of eye colors of Caucasians and Asians on suppression of melatonin secretion by light.

Higuchi S, Motohashi Y, Ishibashi K, Maeda T.

Am J Physiol Regul Integr Comp Physiol. 2007 Mar 1; [Epub ahead of print]

Abstract: This experiment tested effects of human eye pigmentation depending on the ethnic on suppression of nocturnal melatonin secretion by light. Ten healthy Caucasian males with blue, green or light brown irises (light-eyed Caucasians) and eleven Asian males with dark brown irises (dark-eyed Asians) volunteered to participate in the study. The mean ages of the light-eyed Caucasians and dark-eyed Asians were 26.4 +/- 3.2 and 25.3 +/- 5.7 years, respectively. The subjects were exposed to light (1000 lx) for two hours at night. The starting time of exposure was set to two hours before the time of peak salivary melatonin concentration of each subject, which was determined in a preliminary experiment. Salivary melatonin concentration and pupil size were measured before exposure to light and during exposure to light. The percentage of suppression of melatonin secretion by light was calculated. The percentage of suppression of melatonin secretion two hours after the start of bright light exposure was significantly larger in light-eyed Caucasians (88.9 +/- 4.2%) than in dark-eyed Asians (73.4 +/- 20.0%) (p < 0.01). No significant difference was found between pupil sizes in light-eyed Caucasians and dark-eyed Asians. These results suggest that sensitivity of melatonin to light suppression is influenced by eye pigmentation and/or ethnicity.

Monday Maps - Lactase persistence in Europe

I have several maps today. Still intrigued by the lack of the supposed lactase persistence allele (LCT 13910-T) in the 7 European Neolithic skeletons, I was trying to find a map of the frequency of that allele across Europe (or the world). This was mainly an internet search, and I only looked at a few of the published papers. This is what I found:
This one (above) shows the percentage of people who are lactose intolerant (however that was measured??)
This one shows pretty much the same thing, but inverse - those who are lactose tolerant -- here again, highest in Northwest Europe and not all that high in central, eastern, and southeastern europe (where those neolithic skelonts were found)
This one shows the lactose absorption across Europe. This is from the website of Karin Haack, a PhD student interested in "Exploring human diet in prehistory through the genetic trait of lactase persistence". In referring to this map, she says:

"Looking at the map of percentages for lactose absorption in Europe one can see a distinct cline from the north-west to the south east. This is very interesting for the following reason: animals were domesticated in the Near East around 10,000 years ago and then subsequently spread over Europe till animal domesticates reached the British Isles around 6,000 years ago. One would therefore expect populations in the Near East to have highest percentages of lactose absorption and populations in north-western Europe to have lowest percentages of lactose absorption, if lactase persistence was selected for with the domestication of animals and development of dairying. But percentages for lactose absorption are highest in those regions where domesticated animals arrived last in Europe not where animal where domesticated. Therefore the selection for lactase persistence should be a north-western European event which essentially means that there should be multiple origins for lactase persistence all over the world since high percentages occur elsewhere in the world. An indication that there must be multiple origins for lactase persistence is given by my revision of genetic data generated by Hollox et al. (2001)."

Well anyway, one of my points for this long post is that the absence of the LCT 13910 allele in the Neolithic skeletons may not be inconsistent with the relatively high frequency of lactose intolerance in many parts of Europe. There are still many unanswered questions, for me at least. Do we know the allele frequency of 13910-T in different parts of Europe today ?(we probably do) and to what extent is that the causative allele (any physiological evidence?), and finally, to what extent is the phenotype plastic?

Saturday, March 03, 2007

AAPA 2007 abstracts

Check out Dienekes' list of interesting AAPA abstracts... notably: Harpending and Cochran/Hawks:

Understanding human races: the retreat of neutralism.
Henry Harpending
Discussion and debate about human races has been dominated for decades by neutral theory and statistics. Since this literature never posed a real question, it has never produced an answer. Lewontin's 1972 paper with its claim that a value of 1/8 of a statistic like Fst is “small” and that this means that human race differences are insignificant is a staple of our textbooks. Recently geneticists have had a closer look and pointed out that Fst of 1/8 describes differences among sets of half sibs and few claim that half sibs are insignificantly related. Anthony Edwards has shown that the significance of differences is in the correlation structure of a large number of traits, again denying the Lewontin assertion that human differences are small. Alan Templeton in 1998 claimed that human races were less differentiated that races of some other large mammals, but he compared human nuclear DNA statistics with statistics from mtDNA in the other species. An appropriate comparison shows that human are more, not less, differentiated than other large mammal species. Since neutral differences are a passive
record of demographic history they are not very significant for issues of functional biology. Newly available data sources allow us to study the natural selection of race differences instead of their drift. It appears that there is a lot of ongoing evolution in our species and the loci under strong selection on different continents only partially overlap. Human race differences may be increasing rapidly.

Acceleration of adaptive evolution in modern humans.
J. Hawks and G. Cochran
Humans vastly increased in numbers during the past 40,000 years. Recent surveys of human genomic variation have suggested a large surplus of recent positive selection, indicated by excess linkage disequilibrium and skewed SNP frequency spectra. We applied estimates of prehistoric and historic population sizes to estimate the importance of population growth in explaining the number of recent adaptive mutations. Our estimates are consistent with genomic evidence in suggesting that the rate of generation of positively selected genes has increased as much as a hundredfold during the past 40,000 years.

Do skeletal features reflect this genomic evidence of selection? Under positive
selection, rapid appearance of new variants during the terminal Pleistocene and early
Holocene would cause maximal phenotypic change during the last 2000-4000 years. We compared original and published series of Holocene cranial data from Europe, Jordan, Nubia, South Africa, and China, in addition to Late Pleistocene samples from Europe and West Asia, to test the hypothesis that the genomic acceleration in positive selection correlates with phenotypic evolution during this time period. A constellation of features in the face and cranial vault, notably including endocranial volume, changed globally during this time period and documents common patterns of selection in different regions. Holocene changes were similar in pattern and chronologically faster than those at the archaic-modern transition, which themselves were rapid compared to earlier hominid evolution. In genomic and craniometric terms, the origin of modern humans was a minor event compared to more recent evolutionary changes.

Thursday, March 01, 2007

"Why most published research findings are false"

I haven't had the chance to read this closely, but it looks pretty good.

Why Most Published Research Findings Are False

PLoS Medicine 2(8): e124

John P. A. Ioannidis

Summary: There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

Most Published Research Findings Are False—But a Little Replication Goes a Long Way

Ramal Moonesinghe, Muin J. Khoury, A. Cecile J. W. Janssens

PLoS Medicine

some excerpts:

"We know there is a lot of lack of replication in research findings, most notably in the field of genetic associations [1–3]. For example, a survey of 600 positive associations between gene variants and common diseases showed that out of 166 reported associations studied three or more times, only six were replicated consistently [4]. Lack of replication results from a number of factors such as publication bias, selection bias, Type I errors, population stratification (the mixture of individuals from heterogeneous genetic backgrounds), and lack of statistical power [5].
In a recent article in PLoS Medicine, John Ioannidis quantified the theoretical basis for lack of replication by deriving the positive predictive value (PPV) of the truth of a research finding on the basis of a combination of factors. He showed elegantly that most claimed research findings are false [6]. One of his findings was that the more scientific teams involved in studying the subject, the less likely the research findings from individual studies are to be true. The rapid early succession of contradictory conclusions is called the “Proteus phenomenon” [7]. For several independent studies of equal power, Ioannidis showed that the probability of a research finding being true when one or more studies find statistically significant results declines with increasing number of studies."

and in the conclusion:

"In summary, while we agree with Ioannidis that most research findings are false, we clearly demonstrate that replication of research findings enhances the positive predictive value of research findings being true. While this is not unexpected, it should be encouraging news to researchers in their never-ending pursuit of scientific hypothesis generation and testing. Nevertheless, more methodologic work is needed to assess and interpret cumulative evidence of research findings and their biological plausibility. This is especially urgent in the exploding field of genetic associations."

The trickle down power of maternal certainty...maybe

enough said, although I wouldn't exclude other possible explanations for their findings...females are generally closer to their families, therefore this might make for more contact between mothers and kids and the mother's family than between father and kids and father's family.

Altruism towards cousins

Joonghwan Jeon and David M. Buss

Proceedings of the Royal Society B: Biological Sciences (Online) Issue: FirstCite Early Online Publishing

Abstract: Recent research on kin investment shows a matrilateral bias as a function of paternity uncertainty. Kin investment, however, is a special case of kin altruism. We thus hypothesize that psychological adaptations have evolved to regulate cousin-directed altruism according to predictably variable levels of paternity uncertainty in different categories of cousins. We develop a formal mathematical model that predicts that individuals should be most willing to act altruistically towards their mother's sister's (MoSis) children and least willing to act altruistically towards their father's brother's (FaBro) children. Altruism towards father's sister's (FaSis) and mother's brother's (MoBro) children are predicted to fall in between. An empirical study (N=195), assessing expressed altruistic proclivities, confirmed the predictions from the model. Participants expressed willingness-to-help following the descending order: (i) MoSis children, (ii) MoBro children, (iii) FaSis children, and (iv) FaBro children. The psychological variables of emotional closeness, empathic concern and contact frequency showed precisely the same pattern across distinct cousins, providing convergent confirmation of the model. The results support the hypothesis of cousin-specific adaptations sensitive to varying probabilities of paternity uncertainty.

Lactase persistence allele not found in neolithic DNA

Dienekes, Razib and others have already reported on this. The paper just came out this morning.

The skeletons were found in Germany, Hungary, Poland and Lithuania. They were dated to 7,000 to 8,000 years ago (these are the seven neolithic ones).

All seven neolithic samples were homozygous for the non lactase persistent allele 13910- C.
They provide a list of the individuals who worked in the lab and I was surprised by how high the frequency of this non-lactase-persistent allele was- so maybe not so easy to rule out contamination. The authors make the interesting point that contamination of ancient nuclear DNA is not as common as ancient mtDNA contamination. There are some other issues with ancient DNA (allelic dropout), but they seem to have controlled for them pretty thouroughly (I'm not the person to ask though).

Aren't the highest frequencies of 13910-T found in northwestern Europe (see possible clue here)? This is maybe where selection for this allele began (according to haplotype decay analysis - about 10,000 years ago -- with a big confidence interval-- reference in paper), and then spread to other areas in Europe? The dates of these skeletons are pretty close to the middle of the range of when selection might have began.

I just noticed this paper was received for review back in September. What's taking so long?

Absence of the lactase-persistence-associated allele in early Neolithic Europeans

J. Burger , M. Kirchner , B. Bramanti , W. Haak , and M. G. Thomas

PNAS Published online before print February 28, 2007

Abstract: Lactase persistence (LP), the dominant Mendelian trait conferring the ability to digest the milk sugar lactose in adults, has risen to high frequency in central and northern Europeans in the last 20,000 years. This trait is likely to have conferred a selective advantage in individuals who consume appreciable amounts of unfermented milk. Some have argued for the "culture-historical hypothesis," whereby LP alleles were rare until the advent of dairying early in the Neolithic but then rose rapidly in frequency under natural selection. Others favor the "reverse cause hypothesis," whereby dairying was adopted in populations with preadaptive high LP allele frequencies. Analysis based on the conservation of lactase gene haplotypes indicates a recent origin and high selection coefficients for LP, although it has not been possible to say whether early Neolithic European populations were lactase persistent at appreciable frequencies. We developed a stepwise strategy for obtaining reliable nuclear ancient DNA from ancient skeletons, based on (i) the selection of skeletons from archaeological sites that showed excellent biomolecular preservation, (ii) obtaining highly reproducible human mitochondrial DNA sequences, and (iii) reliable short tandem repeat (STR) genotypes from the same specimens. By applying this experimental strategy, we have obtained high-confidence LP-associated genotypes from eight Neolithic and one Mesolithic human remains, using a range of strict criteria for ancient DNA work. We did not observe the allele most commonly associated with LP in Europeans, thus providing evidence for the culture-historical hypothesis, and indicating that LP was rare in early European farmers.

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