Haplogroup predictor from Relative Genetics

Relative Genetics launches its haplogroup predictor. You must register to use it, and you can find matches for your haplotype in addition to having your haplogroup estimated.

My results: RG got my haplogroup wrong, even though I believe it is fairly easy to distinguish from the given estimate. So, try Whit Athey's haplogroup predictor instead, if you don't know your haplogroup and want to have it estimated.

Selection on CFTR gene

Another allele that is rare in Sub-Saharan Africans and has increased in frequency in Caucasoids due to positive selection.

European Journal of Human Genetics (advance online publication)

Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations

Fiorenza Pompei et al.

Abstract

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.

Link

Polymorphism of the G1733A polymorphism in Mediterranean region

American Journal of Human Biology
Volume 17, Issue 6 , Pages 690 - 695

An unexpected wide population variation of the G1733A polymorphism of the androgen receptor gene: Data on the Mediterranean region

E. Esteban

Abstract

The androgen receptor (AR) has been proposed as a candidate gene for several cancers (breast, prostate, uterine endometrium, colon, and esophagus). Ethnicity is considered an associated risk factor for some of these cancers. Several case-control genetic studies have been focused in samples of the main ethnic groups, but little is known about the distribution of risk polymorphisms in current populations with accurate ethnic and/or geographic origins. The A allele of the G1733A polymorphism of the AR gene has been associated with increased risk of prostate cancer. We provide data from this marker in 12 samples from 7 Mediterranean countries such as Spain, Italy (Sardinia), Greece, Turkey, Morocco, Algeria, and Egypt. A sample from Ivory Coast has also been analyzed. The A allele distribution shows a frequency in the Ivory Coast population (65.17%) that contrasts with the low values found in Northern Mediterraneans (mean average value of 13.98%). North African populations present two-times higher frequencies (average value of 27.19%) than Europeans. The wide population variation range found for the A allele strengthens the potential interest of further screening as a baseline to the design of future preventive and population health programs.

Link

Cognitive reserve in aging humans

An interesting new paper which suggests that the fact that human brain function does not decline at least up to 60 years of age, i.e., long after reproductive age, may be linked to the higher inclusive fitness of old individuals who are able to maintain a good cognitive function.

American Journal of Human Biology
Volume 17, Issue 6 , Pages 673 - 689

The aging brain: The cognitive reserve hypothesis and hominid evolution

John S. Allen et al.

Abstract

Compared to other primates, humans live a long time and have large brains. Recent theories of the evolution of human life history stages (grandmother hypothesis, intergenerational transfer of information) lend credence to the notion that selection for increased life span and menopause has occurred in hominid evolution, despite the reduction in the force of natural selection operating on older, especially post-reproductive, individuals. Theories that posit the importance (in an inclusive fitness sense) of the survival of older individuals require them to maintain a reasonably high level of cognitive function (e.g., memory, communication). Patterns of brain aging and factors associated with healthy brain aging should be relevant to this issue. Recent neuroimaging research suggests that, in healthy aging, human brain volume (gray and white matter) is well-maintained until at least 60 years of age; cognitive function also shows only nonsignificant declines at this age. The maintenance of brain volume and cognitive performance is consistent with the idea of a significant post- or late-reproductive life history stage. A clinical model, the cognitive reserve hypothesis, proposes that both increased brain volume and enhanced cognitive ability may contribute to healthy brain aging, reducing the likelihood of developing dementia. Selection for increased brain size and increased cognitive ability in hominid evolution may therefore have been important in selection for increased lifespan in the context of intergenerational social support networks.

Link

HapMap publication explosion

Haplotype map offers new insights into human disease, evolution

Cambridge, MA, Wed., Oct. 26, 2005 – In several papers published this week in Nature, Nature Genetics, PLoS Biology and Genome Research, Broad researchers and an international set of collaborators announce substantial advances in relating human genetic variation to disease and understanding human evolutionary history.

This flurry of high-profile studies are grounded in data described in a significant paper published in the Oct. 27 issue of the journal Nature by an international consortium of more than 200 researchers from Canada, China, Japan, Nigeria, the United Kingdom and the United States. In this paper, the authors describe the common patterns of genetic variation in human DNA samples collected from four sites around the world. The Consortium's findings provide overwhelming evidence for previous scientific work suggesting that genetic variants located physically close to each other are collectively inherited as groups, called haplotypes. The comprehensive catalog of all of these blocks, known as the "HapMap," which is now publicly available to the biomedical research community, has already accelerated the search for gene variants involved in common diseases and brought new insights into the genes involved in human evolution.

...

In line with the Broad Institute's commitment to building critical resources for the scientific community, HapMap data are freely available in several public databases, including the HapMap Data Coordination Center (www.hapmap.org), the NIH-funded National Center for Biotechnology Information's dbSNP (www.ncbi.nlm.nih.gov/SNP/index.html) and the JSNP Database in Japan (snp.ims.u-tokyo.ac.jp). Further information can also be found at the Broad Institute's web site (www.broad.mit.edu).

Read more:

HapMap Could Yield Genetic Clues to Many Diseases Forbes
HapMap Catalogue of Human Genetic Variation Published Bio-IT World
Phase I of HapMap complete The Scientist

Researchers have released a public database of human genetic variation, designed to help scientists study the effects of small genetic differences on health, reports an international consortium in this week's Nature. The findings suggest that only 260,000 to 470,000 single nucleotide polymorphisms (SNPs) are needed to capture all the common genetic variation in the populations studied, despite the fact that there are an estimated 10 million common SNPs in the human genome.

List of papers/editorials/commentaries (most require access):

Nature Deeper into the genome
Nature Genomics: Understanding human diversity
Nature A haplotype map of the human genome

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Nature Genetics Efficiency and power in genetic association studies

We investigated selection and analysis of tag SNPs for genome-wide association studies by specifically examining the relationship between investment in genotyping and statistical power. Do pairwise or multimarker methods maximize efficiency and power? To what extent is power compromised when tags are selected from an incomplete resource such as HapMap? We addressed these questions using genotype data from the HapMap ENCODE project, association studies simulated under a realistic disease model, and empirical correction for multiple hypothesis testing. We demonstrate a haplotype-based tagging method that uniformly outperforms single-marker tests and methods for prioritization that markedly increase tagging efficiency. Examining all observed haplotypes for association, rather than just those that are proxies for known SNPs, increases power to detect rare causal alleles, at the cost of reduced power to detect common causal alleles. Power is robust to the completeness of the reference panel from which tags are selected. These findings have implications for prioritizing tag SNPs and interpreting association studies.

Genome Research
Calibrating a coalescent simulation of human genome sequence variation

Population genetic models play an important role in human genetic research, connecting empirical observations about sequence variation with hypotheses about underlying historical and biological causes. More specifically, models are used to compare empirical measures of sequence variation, linkage disequilibrium (LD), and selection to expectations under a "null" distribution. In the absence of detailed information about human demographic history, and about variation in mutation and recombination rates, simulations have of necessity used arbitrary models, usually simple ones. With the advent of large empirical data sets, it is now possible to calibrate population genetic models with genome-wide data, permitting for the first time the generation of data that are consistent with empirical data across a wide range of characteristics. We present here the first such calibrated model and show that, while still arbitrary, it successfully generates simulated data (for three populations) that closely resemble empirical data in allele frequency, linkage disequilibrium, and population differentiation. No assertion is made about the accuracy of the proposed historical and recombination model, but its ability to generate realistic data meets a long-standing need among geneticists. We anticipate that this model, for which software is publicly available, and others like it will have numerous applications in empirical studies of human genetics.

PLoS Biology The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

Desmond Morris on Symbolic Gestures

A reader alerts me to a few articles in Forbes, one of which caught my attention. Desmond Morris writes about symbolic gestures:

I’ve been to 91 different countries now looking at gestures. For example, as you go south through Europe down through the Mediterranean, gestures become more and more extreme and exaggerated. They’re more frequent and with greater amplitude. When you get to Africa, it tails off again because of the heat. It’s too hot to gesticulate. The climate around the Mediterranean seems to be the ideal climate for gesturing. Also, the Mediterranean cultures have mixed so many times, which has encouraged gestural communication because there have been verbal language barriers to overcome.

Dr. Morris proposes two different explanations for the richness of the gesture repertoire in Mediterranean region, an environmental one (not too hot or too cold), and a cultural one (interaction between different cultures).

I am not sure which one makes more sense. Presumably, one could study the richness of gesturing in coastal areas and port cities around the Mediterranean, and compare them with those from more isolated regions away from the coast. Would we expect people from a busy port to be more expressive with their hands, or less so, because gestures might be more likely to be misinterpreted?

Certainly, the Mediterranean has been navigated for thousands of years, and this would create ideal conditions for the spread of behaviors, including gestures. On the other hand, the Mediterranean has also known its fair share of linguae francae, facilitating verbal communication.

Are gestures really used to overcome language barriers as Dr. Morris suggests? One certainly has to use gestures to communicate with a foreign speaker: verbal communication is impossible. But, I think that one gestures more frequently among his own people, because they are more likely to appreciate and "understand" the meaning of gestures than foreigners. I strongly suspect that populations that are more homogeneous and isolated may be gesturally rich, because gestures are less likely to be misinterprted than in more culturally heterogeneous populations.

What we perhaps need, is for someone to apply phylogenetic methods to the problem of gesture distribution in the manner in which such methods have been applied to linguistic problems. The relationship of languages can often be determined by examining their common vocabulary or grammatical/syntactic features. It would be nice for some student of gestures to determine the relationships of ethnic groups and populations based on their shared gesture repertoires.

MIT researchers fail to recreate Archimedes "death ray"

...and having failed, claim that Archimedes' solar-powered weapon was a "myth".

Teams fail to recreate Archimedes' fabled death ray:

SAN FRANCISCO (AP) — It wasn't exactly the ancient siege of Syracuse, but rather a curious quest for scientific validation.

According to sparse historical writings, the Greek mathematician Archimedes torched a fleet of invading Roman ships by reflecting the sun's powerful rays with a mirrored device made of glass or bronze.

More than 2,000 years later, researchers from the Massachusetts Institute of Technology and the University of Arizona set out to recreate Archimedes' fabled death ray Saturday in an experiment sponsored by the Discovery Channel program MythBusters.

Their attempts to set fire to an 80-year-old fishing boat using their own versions of the device, however, failed to either prove or dispel the myth of the solar death ray.

The MIT team's first attempt with their contraption made of 300 square feet of bronze and glass failed to ignite a fire from 150 feet away. It produced smoldering on the boat's wooden surface but no open flame. A second attempt from about 75 feet away lit only a small fire that burned itself out.

Mike Bushroe of the University of Arizona's Lunar and Planetary Laboratory tried a mirrored system shaped like flower petals, but it failed to produce either smoke or flames.

Peter Rees, executive producer of MythBusters, said the experiment showed Archimedes' death ray was most likely a myth.

"We're not saying it can't be done," Rees said. "We're just saying it's extremely impractical as a weapon of war."

The experiment showed it may be technically possible, but didn't answer whether Archimedes used it to destroy enemy ships, MIT professor David Wallace said.

"Who can say whether Archimedes did it or not?" he said. "He's one of the great mathematical minds in history. I wouldn't want to underestimate his intelligence or ability."

Historical text describes Archimedes defeating a Roman fleet using the ray.

In "Epitome ton Istorion," John Zonaras wrote: "At last in an incredible manner he burned up the whole Roman fleet. For by tilting a kind of mirror toward the sun he concentrated the sun's beam upon it; and owing to the thickness and smoothness of the mirror he ignited the air from this beam and kindled a great flame, the whole of which he directed upon the ships that lay at anchor in the path of the fire, until he consumed them all."

MythBusters also tried to recreate the ray last year, and after failing, declared the story a myth.

"If this weapon had worked, it would have been the equivalent of a nuclear weapon in the ancient world," Rees said.

The sources on Archimedes' mirror:

"When Marcellus withdrew them [his ships] a bow-shot, the old man [Archimedes] constructed a kind of hexagonal mirror, and at an interval proportionate to the size of the mirror he set similar small mirrors with four edges, moved by links and by a form of hinge, and made it the centre of the sun's beams--its noon-tide beam, whether in summer or in mid-winter. Afterwards, when the beams were reflected in the mirror, a fearful kindling of fire was raised in the ships, and at the distance of a bow-shot he turned them into ashes. In this way did the old man prevail over Marcellus with his weapons."

"At last in an incredible manner he [Archimedes] burned up the whole Roman fleet. For by tilting a kind of mirror toward the sun he concentrated the sun's beam upon it; and owing to the thickness and smoothness of the mirror he ignited the air from this beam and kindled a great flame, the whole of which he directed upon the ships that lay at anchor in the path of the fire, until he consumed them all."

Lots more info on similar experiments (Archimedes and his Burning Mirrors)

The science of chat-up lines

Ratings of different categories of chat-up lines:



The descriptions of the categories below:

For the analyses reported here we classified the items into seven groups characterised broadly by the following single-word descriptors. ‘Character’: 5 items demonstrating the man has qualities such as generosity, physical fitness, ability to take control of a situation, and spontaneous wit. ‘Culture’: 5 items. ‘Wealth’: 4 items. ‘Humour’: 6 items involving pre-planned humour. ‘Compliment’: 7 items. ‘Sex’: 7 items with a sexual content. Items that bridged two or more categories, or were difficult to categorise with confidence, were assigned to the miscellaneous group (‘Misc.’: 6 items). Since the number of items per group varied, we used the mean score per item to compare the groups.

The authors don't list all chat-up lines in their seven categories, but the following two were very successful and unsuccessful. Try to guess which was the successful one :)

q34 (Character) It is late at night and a woman is standing at the front of a line of people waiting for a bus. Two young men, talking loudly, obviously drunk, stagger up and push in front of her. A man, who is waiting just behind, walks up to them:

M: Excuse me lads, but I think this lady was first.

One of the young men squares up to the man.

Young Man: What’s it to you then?

M: Come on mate, it’s just manners, we’ve all been waiting here.

The young man stares, considering what to do. He glares at the man, then cursing under his breath walks with his friend to the back of the line.

W: Thanks.

M: That’s ok, they were pushing in front of all of us. My name’s James by the way.

q26 (Compliment) A man is walking around a busy bar as if looking for something. He spots a woman drinking alone at a table, walks up to her smiling, and says:

M: So there you are! I’ve been looking all over for YOU, the girl of my dreams!

Personality and Individual Differences (Article in Press)

Chat-up lines as male sexual displays

Christopher Bale

Abstract

Chat-up lines, and other openings used to initiate a relationship with a woman, can be viewed as male displays. How well does their effectiveness accord with predictions from evolutionary psychology? 205 undergraduates (142 female, 63 male) rated 40 vignettes; in each vignette, a man approached a woman and the raters judged whether she would continue the conversation. Openings involving jokes, empty compliments and sexual references received poor ratings. Those revealing, e.g., helpfulness, generosity, athleticism, ‘culture’ and wealth, were highly rated. Although the length of the vignette—confounded here with item content—affected the rating, differences remained after the effects of length were eliminated. The success of openings which demonstrated culture was predicted from Miller’s (2000) ‘mating mind’ hypothesis; the success of others could be predicted from patterns of parental investment.

Link

Geographic and genetic distance in human populations

As per my previous post, a new study has shown how genetic distance is correlated with geographic distance in human populations. This is similar to another recent study on the same topic. Of interest is the observation that inter-population differences are explained mostly by genetic drift, and less by selection.

Also of interest is the greater genetic differentiation of the Mbuti pygmies and San, above that predicted by geographic distance. The authors attribute this to long-term isolation. This would seem to support my theory about the long-standing differentiation between Paleoafricans and Afrasians. The San and the Mbuti are significantly derived from the Paleoafrican groups who were reproductively isolated from the Afrasians who were the most recent wave of modern humans to spread from Africa into Eurasia and the interior of Africa itself.

PNAS (Early view)

Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa

Sohini Ramachandran et al.

Equilibrium models of isolation by distance predict an increase in genetic differentiation with geographic distance. Here we find a linear relationship between genetic and geographic distance in a worldwide sample of human populations, with major deviations from the fitted line explicable by admixture or extreme isolation. A close relationship is shown to exist between the correlation of geographic distance and genetic differentiation (as measured by FST) and the geographic pattern of heterozygosity across populations. Considering a worldwide set of geographic locations as possible sources of the human expansion, we find that heterozygosities in the globally distributed populations of the data set are best explained by an expansion originating in Africa and that no geographic origin outside of Africa accounts as well for the observed patterns of genetic diversity. Although the relationship between FST and geographic distance has been interpreted in the past as the result of an equilibrium model of drift and dispersal, simulation shows that the geographic pattern of heterozygosities in this data set is consistent with a model of a serial founder effect starting at a single origin. Given this serial-founder scenario, the relationship between genetic and geographic distance allows us to derive bounds for the effects of drift and natural selection on human genetic variation.

Link

Natural selection on the human genome

Nature 437, 1153-1157

Natural selection on protein-coding genes in the human genome

Carlos D. Bustamante et al.

Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection. The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly, with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection, and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations. Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees.

Link

The genetic legacy of the Manchu

A new paper in AJHG has identified a unique haplotype shared by many people from northeastern China and Mongolia. This haplotype belongs to haplogroup C3c, and is estimated to be about five centuries old. Its very recent spread corresponds with the rise to power of the Qing dynasty. As the authors write:

We reasoned that the events leading to the spread of this lineage might have been recorded in the historical record, as well as in the genetic record. The spread must have occurred after the cluster's TMRCA (∼500 years ago, corresponding to about A.D. 1500) and, most likely, before the Xibe migration in 1764. Notable features are the occurrence of the lineage in seven different populations but its apparent absence from the most populous Chinese ethnic group, the Han. A major historical event took place in this part of the world during this period—namely, the Manchu conquest of China and the establishment of the Qing dynasty, which ruled China from 1644 to 1912. This dynasty was founded by Nurhaci (1559–1626) and was dominated by the Qing imperial nobility, a hereditary class consisting of male-line descendants of Nurhaci's paternal grandfather, Giocangga (died 1582), with >80,000 official members by the end of the dynasty (Elliott 2001). The nobility were highly privileged; for example, a ninth-rank noble annually received ∼11 kg of silver and 22,000 liters of rice and maintained many concubines. A central part of the Qing social system was the army, the Eight Banners, which was made up of separate Manchu, Mongolian, and Chinese (Han) Eight Banners. The nobility occupied high ranks in the Manchu Eight Banners but not in the Mongolian or Chinese Eight Banners; the Manchu Eight Banners were recruited from the Manchu, Mongolian, Daur, Oroqen, Ewenki, Xibe, and a few other populations. A social mechanism was thus established that would have led to the increase of the specific Y lineage carried by Giocangga and Nurhaci and to its spread into a limited number of populations. We suggest that this lineage was the Manchu lineage.

Due to the very recent spread of this "Manchu" haplotype, it may be possible to find descendants of the Qing imperial nobility and test them. Presumably, they should have a high frequency of this haplotype. As the authors point out, the tumultuous events of recent times, have obscured the geneaological records. It may still be worthwhile to track such descendants though, or even remains of Qing noblemen. This would be a test for the validity of this theory.

An alternative explanation may be that the haplotype has been positively selected. There is, however, no direct evidence for this, and the limited geographical distribution of the haplotype may argue against this explanation:



American Journal of Human Genetics (early view)

Recent Spread of a Y-Chromosomal Lineage in Northern China and Mongolia

Yali Xue et al.

We have identified a Y-chromosomal lineage that is unusually frequent in northeastern China and Mongolia, in which a haplotype cluster defined by 15 Y short tandem repeats was carried by ∼3.3% of the males sampled from East Asia. The most recent common ancestor of this lineage lived 590 ± 340 years ago (mean ± SD), and it was detected in Mongolians and six Chinese minority populations. We suggest that the lineage was spread by Qing Dynasty (1644–1912) nobility, who were a privileged elite sharing patrilineal descent from Giocangga (died 1582), the grandfather of Manchu leader Nurhaci, and whose documented members formed ∼0.4% of the minority population by the end of the dynasty.

Link

The origin of an HIV-Resistance Allele

Via John Hawks. This study is a good example of how non-uniform selection can change allele frequencies in a way that an allele may reach its highest frequency in a region different from the one where it originated. See also HIV Resistance mutation in the Bronze Age.

PLoS Biology Volume 3, Issue 11

The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

John Novembre et al.

The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

Link

"Junk" no more

UCSD study shows 'junk' DNA has evolutionary importance

Genetic material derisively called "junk" DNA because it does not contain the instructions for protein-coding genes and appears to have little or no function is actually critically important to an organism's evolutionary survival, according to a study conducted by a biologist at the University of California, San Diego.

In the October 20 issue of Nature, Peter Andolfatto, an assistant professor of biology at UCSD, shows that these non-coding regions play an important role in maintaining an organism's genetic integrity. In his study of the genes from the fruit fly Drosophila melanogaster, he discovered that these regions are strongly affected by natural selection, the evolutionary process that preferentially leads to the survival of organisms and genes best adapted to the environment.

Andolfatto's findings are important because the similarity of genome sequences in fruit flies, worms and humans suggest that similar processes are probably responsible for the differences between humans and their close evolutionary relatives.

"Sequencing of the complete genome in humans, fruit flies, nematodes and plants has revealed that the number of protein-coding genes is much more similar among these species than expected," he says. "Curiously, the largest differences between major species groups appear to be the amount of 'junk' DNA rather than the number of genes."

Using a recently developed population genetic approach, Andolfatto showed in his study that these expansive regions of "junk" DNA--which in Drosophila accounts for about 80 percent of the fly's total genome--are evolving more slowly than expected due to natural selection pressures on the non-protein-coding DNA to remain the same over time.

"This pattern most likely reflects resistance to the incorporation of new mutations," he says. "In fact, 40 to 70 percent of new mutations that arise in non-coding DNA fail to be incorporated by this species, which suggests that these non-protein-coding regions are not 'junk,' but are somehow functionally important to the organism."

Andolfatto also found that "junk" regions exhibit an unusually large amount of functional genetic divergence between different species of Drosophila, further evidence that these regions are evolutionarily important to organisms. This implies that, like evolutionary changes to proteins, changes to these "junk" parts of the genome also play an important role in the evolution of new species.

"Protein evolution has traditionally been emphasized as a key facet of genome evolution and the evolution of new species," says Andolfatto. "The degree of protein sequence similarity between humans and chimpanzees, and other closely-related but morphologically distinct taxa, has prompted several researchers to speculate that most adaptive differences between taxa are due to changes in gene regulation and not protein evolution. My results lend support to this view by demonstrating that regulatory changes have been of great importance in the evolution of new Drosophila species."

Nature 437, 1149-1152

Adaptive evolution of non-coding DNA in Drosophila

Peter Andolfatto

Abstract

A large fraction of eukaryotic genomes consists of DNA that is not translated into protein sequence, and little is known about its functional significance. Here I show that several classes of non-coding DNA in Drosophila are evolving considerably slower than synonymous sites, and yet show an excess of between-species divergence relative to polymorphism when compared with synonymous sites. The former is a hallmark of selective constraint, but the latter is a signature of adaptive evolution, resembling general patterns of protein evolution in Drosophila1, 2. I estimate that about 40–70% of nucleotides in intergenic regions, untranslated portions of mature mRNAs (UTRs) and most intronic DNA are evolutionarily constrained relative to synonymous sites. However, I also use an extension to the McDonald–Kreitman test3 to show that a substantial fraction of the nucleotide divergence in these regions was driven to fixation by positive selection (about 20% for most intronic and intergenic DNA, and 60% for UTRs). On the basis of these observations, I suggest that a large fraction of the non-translated genome is functionally important and subject to both purifying selection and adaptive evolution. These results imply that, although positive selection is clearly an important facet of protein evolution, adaptive changes to non-coding DNA might have been considerably more common in the evolution of D. melanogaster.

Link

Correlation of genetic distance with geographic distance along migratory routes

This news item from the University of Michigan speaks of a new study on human origins. See also, a related National Geographic story. I will blog more about it once it appears in the PNAS site.

Human genetic diversity supports 'Out of Africa' model

ANN ARBOR, Mich.—Small groups of settlers expanding outward from Africa are the most likely progenitors of the modern human population worldwide, according to a new study by researchers at the University of Michigan and Stanford University.

Researchers used computer modeling to examine a "serial founder effect" scenario as a possible explanation for the relationship between human populations' genetic and geographic distance from Africa, which are highly correlated, according to Noah Rosenberg, assistant research professor at the U-M Life Sciences Institute. He is co-author of the study, which appears in Proceedings of the National Academy of the Sciences.

Geographic distance very accurately predicted the genetic distance between populations. The more similar the genes, the shorter the geographic distance between any two people. The genetic diversity of populations was found to be greatest in Africa and least in the Americas.

The study assumes that there was a single ancestral group, and that subsets of the group expanded and colonized new locations outward from its initial starting point. A subset of settlers populated a new area, and as they did so, their genetic variation declined.

"No geographic location outside Africa accounts as well for the patterns of genetic diversity in the model," Rosenberg said. "If we assume that humans started at one location in Africa, there is an excellent fit of genetic variation to geographic distance. Every single point in Africa that was tested as a possible site of origin has more explanatory power than every site outside of Africa."

"We tried to explain this pattern of genetic and geographic distance using what might have happened in human history," said Rosenberg. "The original group populates a new area, but only some of the people from the original group move to the new area, so there is less genetic variation in the sub-group."

The "Out of Africa" model in paleoanthropology supposes that modern humans evolved within the African continent and migrated around the world. A counter-argument is the "multiregional" hypothesis, which holds that pre-humans left Africa and became modern humans at several locations around the globe. Rosenberg's latest data supports the out-of-Africa model.

A next step for researchers is to add genetic variants that predispose people to genetic diseases into the computer models.

"I'd like to link the geographic distribution of genetic diseases to human evolution," said Rosenberg. "This kind of work can help us figure out the extent to which the genetic factors responsible for globally distributed diseases are the same in all populations."

YHRD Update

YHRD, the Y-chromosome haplotype reference database has been updated with many new populations, and additional markers typed for samples that were already in the database. It is time to search for new matches!

400-year old Yakut DNA

Autosomal STRs and mtDNA HVSI were studied in five Yakut individuals. Interestingly, using the autosomal markers the researchers could prove or exclude the possibility of familial relationships between some of them.

The Yakut live in NE Siberia, and are believed to have originated in Central Asia. Interestingly, the single Caucasoid mtDNA sequence in Yakuts could be plausibly of Central Asian origin, but their Mongoloid sequences are unlike those of their Siberian neighbors. The conclusions of the study:

The molecular data obtained from the archaeological samples studied bring new elements to the understanding of the origin and evolution of the Yakut population, as well as the kinship systems and social structures of the ancient Yakut population. Our results demonstrated the diversity of the sepulchral organization of the Quaternary terrace burial sites, which seem to be according to the degree of social or genetic kinship of the subjects. Moreover, the comparison of genetic data obtained
from ancient Yakut samples with Eurasian populations revealed 1) the presence of maternal lineages specific to the Yakut population; 2) the relative continuity of some of them, which could be considered as ‘‘founder haplotypes;’’ and 3) no support for the putative Central Asian origin of these ancient samples (except with the HV1 sequence of West Eurasian origin). Nevertheless, these preliminary results are inevitably constrained by the sample size, and new archaeological samples could provide more comprehensive insights into Yakut population history and validate/invalidate the hypotheses previously put forward.

American Journal of Physical Anthropology (Early view)

Molecular Genetic Analysis of 400-Year-Old Human Remains Found in Two Yakut Burial Sites

François-Xavier Ricaut et al.

Abstract

The excavation of five frozen graves at the Sytygane Syhe and Istekh-Myrane burial sites (dated at 400 years old) in central Yakutia revealed five human skeletons belonging to the Yakut population. To investigate the origin and evolution of the Yakut population as well as the kinship system between individuals buried in these two sites, DNA was extracted from bone samples and analyzed by autosomal short tandem repeats (STRs) and by sequencing hypervariable region I (HV1) of the mitochondrial DNA (mtDNA) control region. The results showed a diversity of sepulchral organizations linked probably to the social or genetic background of the subjects. Comparison of STR profiles, mitochondrial haplotypes, and haplogroups with data from Eurasian populations indicated affinities with Asian populations and suggested a relative specificity and continuity of part of the Yakut mitochondrial gene pool during the last five centuries. Moreover, our results did not support a Central Asian (with the exception of maternal lineage of West Eurasian origin) or Siberian origin of the maternal lineages of these ancient Yakut subjects, implying an ethnogenesis of the Yakut population probably more complex than previously proposed.

Link