Things that smell nice to both humans and mice

PLoS ONE doi: 10.1371/journal.pone.0004209

Humans and Mice Express Similar Olfactory Preferences

Nathalie Mandairon et al.

Abstract

In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.

Link

Sons of billionaires

From the paper:

For species where one sex has more variable reproductive success (males in polygynous species), the TWH predicts that 1) a mother with more resources to invest would be advantaged by producing a son, as a successful son would out-compete a successful daughter (constrained to a less variable reproductive rate), and 2) a mother with less resources to invest would be advantaged by producing a daughter, as her daughter would out-reproduce an unsuccessful son. Alternatively, if sons are more costly than daughters, only mothers in good condition could bear this cost [2].

PLoS ONE doi: 10.1371/journal.pone.0004195

A Trivers-Willard Effect in Contemporary Humans: Male-Biased Sex Ratios among Billionaires

Elissa Z. Cameron, Fredrik Dalerum

Abstract

Background

Natural selection should favour the ability of mothers to adjust the sex ratio of offspring in relation to the offspring's potential reproductive success. In polygynous species, mothers in good condition would be advantaged by giving birth to more sons. While studies on mammals in general provide support for the hypothesis, studies on humans provide particularly inconsistent results, possibly because the assumptions of the model do not apply.

Methodology/Principal Findings

Here, we take a subset of humans in very good condition: the Forbe's billionaire list. First, we test if the assumptions of the model apply, and show that mothers leave more grandchildren through their sons than through their daughters. We then show that billionaires have 60% sons, which is significantly different from the general population, consistent with our hypothesis. However, women who themselves are billionaires have fewer sons than women having children with billionaires, suggesting that maternal testosterone does not explain the observed variation. Furthermore, paternal masculinity as indexed by achievement, could not explain the variation, since there was no variation in sex ratio between self-made or inherited billionaires.

Conclusions/Significance

Humans in the highest economic bracket leave more grandchildren through sons than through daughters. Therefore, adaptive variation in sex ratios is expected, and human mothers in the highest economic bracket do give birth to more sons, suggesting similar sex ratio manipulation as seen in other mammals.

Link

IQ and death from unintentional injury

Am J Epidemiol. 2009 Jan 15. [Epub ahead of print]

IQ in Early Adulthood, Socioeconomic Position, and Unintentional Injury Mortality by Middle Age: A Cohort Study of More Than 1 Million Swedish Men.

Batty GD, Gale CR, Tynelius P, Deary IJ, Rasmussen F.

The authors evaluated the little-examined association between intelligence (IQ) and injury mortality and, for the first known time, explored the extent to which IQ might explain established socioeconomic inequalities in injury mortality. A nationwide cohort of 1,116,442 Swedish men who underwent IQ testing at about 18 years of age was followed for mortality experience for an average of 22.6 years. In age-adjusted analyses in which IQ scores were classified into 4 groups, relative to the highest scoring category, the hazard ratio in the lowest was elevated for all injury types: poisonings (hazard ratio (HR) = 5.82, 95% confidence interval (CI): 4.25, 7.97), fire (HR = 4.39, 95% CI: 2.51, 7.77), falls (HR = 3.17, 95% CI: 2.19, 4.59), drowning (HR = 3.16, 95% CI: 1.85, 5.39), and road injury (HR = 2.17, 95% CI: 1.91, 2.47). Dose-response effects across the full IQ range were evident (P-trend < 0.001). Control for potential covariates, including socioeconomic position, had little impact on these gradients. When socioeconomic disadvantage-indexed by parental and subject's own occupational social class-was the exposure of interest, IQ explained a sizable portion (19%-86%) of the relation with injury mortality. These findings suggest that IQ may have an important role both in the etiology of injuries and in explaining socioeconomic inequalities in injury mortality.

Link

Y chromosomes and mtDNA of Koreans

Table 2 has a very useful listing of mtDNA haplogroup frequencies in several East Asian populations.

Table 5 has admixture estimates of NE and SE Asians in Korean populations; notice the gender asymmetry, with males of more southern origin than females.

Table S3 (Excel) has Y-chromosome haplogroup frequencies.

From the paper:

What could be the origin of the male-biased southern contribution to Korean gene pool illustrated, for example, by haplogroups O-M122 (42.2%) and O-SRY465 (20.1%) [29]. Recent molecular genetic analyses and the geographical distribution of haplogroup O-M122 lineages, found widely throughout East Asia at high frequencies (especially in southern populations and China), have suggested a link between these Y-chromosome expansions and the spread of rice agriculture in East Asia [62]–[64]. In general, Y-chromosomes might be spread via a process of demic diffusion during the early agricultural expansion period [65], [66]. If this interpretation were substantiated, the spatial pattern of Y-haplogroup O would imply a genetic contribution to Korea through the spread of male-mediated agriculture.

PLoS ONE 10.1371/journal.pone.0004210

The Peopling of Korea Revealed by Analyses of Mitochondrial DNA and Y-Chromosomal Markers

Han-Jun Jin, Chris Tyler-Smith, Wook Kim

Abstract

Background

The Koreans are generally considered a northeast Asian group because of their geographical location. However, recent findings from Y chromosome studies showed that the Korean population contains lineages from both southern and northern parts of East Asia. To understand the genetic history and relationships of Korea more fully, additional data and analyses are necessary.

Methodology and Results

We analyzed mitochondrial DNA (mtDNA) sequence variation in the hypervariable segments I and II (HVS-I and HVS-II) and haplogroup-specific mutations in coding regions in 445 individuals from seven east Asian populations (Korean, Korean-Chinese, Mongolian, Manchurian, Han (Beijing), Vietnamese and Thais). In addition, published mtDNA haplogroup data (N = 3307), mtDNA HVS-I sequences (N = 2313), Y chromosome haplogroup data (N = 1697) and Y chromosome STR data (N = 2713) were analyzed to elucidate the genetic structure of East Asian populations. All the mtDNA profiles studied here were classified into subsets of haplogroups common in East Asia, with just two exceptions. In general, the Korean mtDNA profiles revealed similarities to other northeastern Asian populations through analysis of individual haplogroup distributions, genetic distances between populations or an analysis of molecular variance, although a minor southern contribution was also suggested. Reanalysis of Y-chromosomal data confirmed both the overall similarity to other northeastern populations, and also a larger paternal contribution from southeastern populations.

Conclusion

The present work provides evidence that peopling of Korea can be seen as a complex process, interpreted as an early northern Asian settlement with at least one subsequent male-biased southern-to-northern migration, possibly associated with the spread of rice agriculture.

Link

Ancient mtDNA from Iceland

From the paper:

Using the sequence data described in Table 1, we obtained an estimate of 58% ancestry from Scotland and Ireland for contemporary Icelanders (95% C.I.: 44.6–71.2%). In comparison, the IEMS [DP: Iceland Early Medieval Sample] yielded an estimate of 64.7% (95% C.I.: 36.8–90.3%), indicating a similar excess of matrilineal ancestry from Scotland and Ireland.

PLoS Genetics doi: 10.1371/journal.pgen.1000343

Sequences From First Settlers Reveal Rapid Evolution in Icelandic mtDNA Pool

Agnar Helgason et al.

Abstract

A major task in human genetics is to understand the nature of the evolutionary processes that have shaped the gene pools of contemporary populations. Ancient DNA studies have great potential to shed light on the evolution of populations because they provide the opportunity to sample from the same population at different points in time. Here, we show that a sample of mitochondrial DNA (mtDNA) control region sequences from 68 early medieval Icelandic skeletal remains is more closely related to sequences from contemporary inhabitants of Scotland, Ireland, and Scandinavia than to those from the modern Icelandic population. Due to a faster rate of genetic drift in the Icelandic mtDNA pool during the last 1,100 years, the sequences carried by the first settlers were better preserved in their ancestral gene pools than among their descendants in Iceland. These results demonstrate the inferential power gained in ancient DNA studies through the application of population genetics analyses to relatively large samples.

Link

Selection on human mtDNA from ratio of nonsynonymous to synonymous mutations

Molecular Biology and Evolution, doi:10.1093/molbev/msp005

Temporal trails of natural selection in human mitogenomes

Sankar Subramanian

Abstract

Mildly deleterious mutations initially contribute to the diversity of a population but later they are selected against at high frequency and are eliminated eventually. Using over 1500 complete human mitochondrial genomes along with those of Neanderthal and Chimpanzee, I provide empirical evidence for this prediction by tracing the footprints of natural selection over time. The results show a highly significant inverse relationship between the ratio of nonsynonymous- to synonymous divergence (dN/dS) and the age of human haplogroups. Furthermore this study suggests that slightly deleterious mutations constitute up to 80% of the mitochondrial amino acid replacement mutations detected in human populations and that over the last 500,000 years these mutations have been gradually removed.

Link

Population history of ancient Egyptians

The non-inclusion of population samples from outside Egypt for comparison makes it difficult to assess the population affinities of ancient Egyptians. Nonetheless, this study is to be commended for trying different biodistance measures on the skeletal samples. From the paper:

The relative uniqueness of Gebel Ramlah suggests that this particular Neolithic group did not contribute substantially to the ancestry of subsequent predynastic Nile Valley groups. It is important to note that Gebel Ramlah is also geographically distant from the Nile Valley. Similarly, because the Greek Egyptian sample is an outlier across MDS plots, genetic isolation from local Egyptians seems likely.

American Journal of Physical Anthropology doi: 10.1002/ajpa.20976

Further analysis of the population history of ancient Egyptians

Michael A. Schillaci, Joel D. Irish, Carolan C.E. Wood

Abstract

The origins of state formation in ancient Egypt have been the focus of recent research utilizing biological data to test hypotheses regarding in situ development of local groups, or large-scale in-migration, possibly by an invading army. The primary goal of the present research is to further test these hypotheses. Our secondary goal is to compare different distance measures and assess how they might affect interpretation of population history. We analyze craniodental nonmetric data using several different measures of biological distance, as well as a method for estimating group diversity using multidimensional scaling of distance estimates. Patterns of biological variation and population relationships were interpreted in temporal and geographic contexts. The results of our analyses suggest that the formation of the ancient Egyptian state likely included a substantial in situ process, with some level of contribution by outside migrants probable. The higher level of population structure in Lower Egypt, relative to Upper Egypt, suggests that such influence and migration by outsiders may not have been widespread geographically. These findings support, but serve to refine further those obtained by the second author in a previous study. Moreover, our comparison of distance measures indicates that the choice of measure can influence identification and interpretation of the microevolutionary processes shaping population history, despite being strongly correlated with one another.

Link

mtDNA of Tunisian centenarians

Mech Ageing Dev. 2008 Dec 24.

Data from complete mtDNA sequencing of Tunisian centenarians: Testing haplogroup association and the "golden mean" to longevity.

Costa MD, Cherni L, Fernandes V, Freitas F, Ammar El Gaaied AB, Pereira L.

Since the mitochondrial theory of ageing was proposed, mitochondrial DNA (mtDNA) diversity has been largely studied in old people, however complete genomes are still rare, being limited to Japanese and UK/US samples. In this work, we evaluated possible longevity associated polymorphisms/haplogroups in an African population, from Tunisia, by performing complete mtDNA sequencing. This population has a mixed Eurasian/sub-Saharan mtDNA gene pool, which could potentially facilitate the evaluation of association for sub-Saharan lineages. Sub-Saharan haplogroups were shown to be significantly less represented in centenarians (9.5%) than in controls (54.5%), but it is not possible to rule out an influence of population structure, which is high in these populations. No recurrent polymorphism were more frequent in centenarians than in controls, and although the Tunisian centenarians presented less synonymous and replacement polymorphisms than controls, this difference was not statistically significant. So far, it does not seem that centenarians have significantly less mildly deleterious substitutions, not only in Tunisia but also in Japanese and UK/US samples, as tested here, not favouring a "golden mean" to longevity.

Link

More on Lebanese Phoenicians or mixing Science and Politics

The BBC has a story on Divided Lebanon's common genes.

Dr Zalloua says in Lebanon the Phoenician signature is distributed equally among different groups and that the overall genetic make-up of the Lebanese is proving to be similar across various backgrounds.

"Whether you take a Christian village in the north of Lebanon or a Muslim village in the south, the DNA make-up of its residents is likely to be identical," says Dr Zalloua.

But, from another older BBC story referring to the actual study:

The team analysed the Y chromosomes of 926 Lebanese males and found that patterns of male genetic variation in Lebanon fell more along religious lines than along geographical lines.

and from the study itself:

In the present study, 926 Lebanese men were typed with Y-chromosomal SNP and STR markers, and unusually, male genetic variation within Lebanon was found to be more strongly structured by religious affiliation than by geography.We therefore tested the hypothesis that migrations within historical times could have contributed to this situation. Y-haplogroup J*(xJ2) was more frequent in the putative Muslim source region (the Arabian Peninsula) than in Lebanon, and it was also more frequent in Lebanese Muslims than in Lebanese non-Muslims. Conversely, haplogroup R1b was more frequent in the putative Christian source region (western Europe) than in Lebanon and was also more frequent in Lebanese Christians than in Lebanese non-
Christians.

If a Christian village and a Muslim village are likely to have "identical" DNA makeup, then why is genetic variation strongly structured by religious affiliation and not by geography?

Since contradictions don't exist in nature, the explanation is simple: in the published scientific article, which had to go through peer-review, someone could not claim that there are no differences between Christian and Muslim Lebanese. But, to the polloi of Lebanon, it is apparently alright to sell a vision of national unity and identity.

I don't know what % of modern Lebanese are descended from Phoenicians, but I detest the idea of mixing science with politics.

More on the topic of "Lebanese Phoenicians":

1. Muslim and Christian Lebanese or Hasty Conclusions in Human Population Genetics
2. Christian and Muslim Lebanese do differ from each other after all
3. "Phoenician" Y-chromosomes

Concurrent but distinctive migrations into the Americas

As usual with papers such as this, it is important to note that their age estimates depend on (i) the assumption that coalescence ages of lineages correspond to migration events (in general, they do not), and (ii) the mutation rate used to estimate such ages, which may be time-dependent. In this paper:

We propose here for the first time a new mutation rate taking into account the previous estimates reported by Mishmar [35] for all coding-region base substitutions and by Kivisild [36] for only synonymous transitions. With three decimal digits used throughout, the rounded values were 5140 years per coding-region substitution and 6760 years per synonymous transition, respectively. The rho estimated (average distance of the haplotypes of a clade from the respective root) human coalescence times are then 202 kya according to Mishmar et al. [35] and 160 kya according to Kivisild et al.

The geographic patterns (Pacific coast vs. inland route) seem to be more robust than the conclusions about the supposed ages of the migrations and their temporal concurrency.

The ScienceNews reporting has some contrary views. Some related posts:

1. Language spread rates in the Americas
2. Earliest human occupation of southern South America
3. Three-stage colonization model for Americas reconsidered
4. Craniofacial shape variation and Native American origins

Current Biology doi:10.1016/j.cub.2008.11.058

Distinctive Paleo-Indian Migration Routes from Beringia Marked by Two Rare mtDNA Haplogroups

Ugo A. Perego et al.

Summary

Background

It is widely accepted that the ancestors of Native Americans arrived in the New World via Beringia approximately 10 to 30 thousand years ago (kya). However, the arrival time(s), number of expansion events, and migration routes into the Western Hemisphere remain controversial because linguistic, archaeological, and genetic evidence have not yet provided coherent answers. Notably, most of the genetic evidence has been acquired from the analysis of the common pan-American mitochondrial DNA (mtDNA) haplogroups. In this study, we have instead identified and analyzed mtDNAs belonging to two rare Native American haplogroups named D4h3 and X2a.

Results

Phylogeographic analyses at the highest level of molecular resolution (69 entire mitochondrial genomes) reveal that two almost concomitant paths of migration from Beringia led to the Paleo-Indian dispersal approximately 15–17 kya. Haplogroup D4h3 spread into the Americas along the Pacific coast, whereas X2a entered through the ice-free corridor between the Laurentide and Cordilleran ice sheets. The examination of an additional 276 entire mtDNA sequences provides similar entry times for all common Native American haplogroups, thus indicating at least a dual origin for Paleo-Indians.

Conclusions

A dual origin for the first Americans is a striking novelty from the genetic point of view, and it makes plausible a scenario positing that within a rather short period of time, there may have been several entries into the Americas from a dynamically changing Beringian source. Moreover, this implies that most probably more than one language family was carried along with the Paleo-Indians.

Link

Culture, population structure, and low genetic diversity in humans

As I have mentioned in a previous entry, the genetic structure of human populations has been interpreted as the result of a process of "serial bottlenecks", starting from the major "Out of Africa" bottleneck, and followed by a series of other ones, as humans colonized the world. Bottlenecks reduce genetic diversity, but so does selection, and it is imperative to directly sample genetic diversity of past populations, to see how well they conform with the expectations of the "serial bottlenecks" theory, i.e., whether reduced diversity is due to descent from a few individuals whose progeny transcended the bottleneck, or due to selection, which suppresses genetic variation by removing some alleles from the gene pool.

This paper argues in favor of selection as a mechanism for keeping genetic diversity (and hence effective population size) at low levels. This selection process, is not, however, envisioned as affecting the species as a whole, but rather proceeded in its own way in regional subsets of humans. These groups did not exchange genes randomly with other such groups, but rather according to their degree of cultural similarity.

John Hawks has an extensive post on this article, which I recommend.

PNAS doi:10.1073/pnas.0809194105

Culture, population structure, and low genetic diversity in Pleistocene hominins

L.S. Premo, Jean-Jacques Hublin

Abstract

Paleogenomic research has shown that modern humans, Neanderthals, and their most recent common ancestor have displayed less genetic diversity than living great apes. The traditional interpretation that low levels of genetic diversity in modern humans resulted from a relatively recent demographic bottleneck cannot account for similarly low levels of genetic diversity in Middle Pleistocene hominins. A more parsimonious hypothesis proposes that the effective population size of the human lineage has been low for more than 500,000 years, but the mechanism responsible for suppressing genetic diversity in Pleistocene hominin populations without similarly affecting that of their hominoid contemporaries remains unknown. Here we use agent-based simulation to study the effect of culturally mediated migration on neutral genetic diversity in structured populations. We show that, in populations structured by culturally mediated migration, selection can suppress neutral genetic diversity over thousands of generations, even in the absence of bottlenecks or expansions in census population size. In other words, selection could have suppressed the effective population size of Pleistocene hominins for as long as the degree of cultural similarity between regionally differentiated groups played an important role in mediating intraspecific gene flow.

Link

Viaggio nella Calabria Greca - Ταξίδι στην Ελληνική Καλαβρία

An interesting documentary by alexspil on the Greeks of Calabria. Description:

"Viaggio nella Calabria Greca...insieme a un ministro!"
In questo film viene documentata la visita del vice ministro esteri Greco nella zona ellenofona della Calabria, ma anche vari aspetti culturali interessanti di questa minoranza, come per esempio la lingua, la storia, l'arte,delle testiomonianze ecc. La durata totale del documentario è di 70 minuti, ed è diviso in 8 parti. --------------- ------------------- ------------------ ----------------- ΕΛΛΗΝΙΚΑ: "Περιήγηση στην Ελληνόφωνη Καλαβρία...παρέα με έναν υπουργό!"
Το ντοκιμαντέρ αυτό καταγράφει την επίσκεψη του Υφ.Εξωτερικών της Ελλάδας στα ελληνόφωνα χωριά της Καλαβρίας, καθώς και διάφορα ενδιαφέροντα πολιτιστικά στοιχεία αυτής της μειονότητας, όπως π.χ. γλώσσα, ιστορία, τέχνες , διάφορες μαρτυρίες κ.α. Η συνολική του διάρκεια είναι 70 λεπτά, και έχει χωριστεί σε 8 μέρη.

Part 1/8:



The complete YouTube playlist.

Language spread rates in the Americas

This paper deals with the issue of how a language family's range (how geographically dispersed it is) provides information about its age (how old it is).

I believe that a similar methodology should be applied to the spread of gene variants as well (e.g., Y-chromosome haplogroups). At present, haplogroup ages are estimated only by internal (genetic) information, e.g., the diversity of linked STR loci. However, as I have argued before, there are additional pieces of information: (i) how big the haplogroup is, and (ii) how geographically dispersed it is. Both (i) and (ii) depend on a haplogroup's age.


CURRENT ANTHROPOLOGY Volume 49, Number 6, December 2008 DOI: 10.1086/592436

Language Spread Rates and Prehistoric American Migration Rates


Johanna Nichols

Abstract

Spread rates for language families can be calculated from the family's range (which is generally known rather precisely) and age (which is only rarely known precisely but can often be estimated with useful accuracy). Spread rates are calculated here for a number of different language families and subfamilies in different cultural and economic contexts. Deliberate long-distance migrations, imperial conquest, and transport using wheels or sails make for very rapid spread rates. The rate of prestate, pretransport spreads depends primarily on ecology (latitude, coast vs. interior, mountains, vegetation, climate); presence versus absence of food production and movement into inhabited versus abandoned land have little impact on spread rates. This fact makes rates of recent language spreads applicable to early prehistory, where they can be used to model prehistoric colonization rates. Average rates for various ecologies are calculated for a spread from a North American entry point to the archaeological site at Monte Verde, Chile (14,500 calendar years ago). The time required gives a latest possible date for the first settlement of the Americas. Entry dates postdating the end of glaciation all require implausibly fast rates of spread.

Link

Waist-to-Hip Ratio across cultures

CURRENT ANTHROPOLOGY Volume 49, Number 6, December 2008
DOI: 10.1086/593036

Waist-to-Hip Ratio across Cultures: Trade-Offs between Androgen- and Estrogen-Dependent Traits


Elizabeth Cashdan

Abstract

A gynoid pattern of fat distribution, with small waist and large hips (low waist-to-hip ratio, or WHR) holds significant fitness benefits for women: women with a low WHR of about 0.7 are more fecund, are less prone to chronic disease, and (in most cultures) are considered more attractive. Why, then, do nearly all women have a WHR higher than this putative optimum? Is the marked variation in this trait adaptive? This paper first documents the conundrum by showing that female WHR, especially in non-Western populations, is higher than the putative optimum even among samples that are young, lean, and dependent on traditional diets. The paper then proposes compensating benefits to a high WHR that can explain both its prevalence and variation in the trait. The evidence indicates that the hormonal profile associated with high WHR (high androgen and cortisol levels, low estrogens) favors success in resource competition, particularly under stressful and difficult circumstances, even though this carries fitness costs in fecundity and health. Adrenal androgens, in particular, may play an important role in enabling women to respond to stressful challenges.

Link

Nicholas Christakis on the Anthroposphere

An interesting answer from the Edge World Question Center 2009. The part in italics reminds me of a previous post I made on Rise of diseases in modern societies is not (usually) due to genetic or environmental factors:

This is a simple consequence of the one reality of life, namely death. The total mortality of the population is always 100%, as we all eventually die. Therefore the prevalence of a particular disease (which brings us closer to death) does not depend exclusively on factors (genetic or environmental) that cause the disease. It also depends on other diseases or lethal factors which might beat them to the punch.

In previous centuries for example, death during childbirth, tuberculosis, death in war, famine etc. were more prevalent. Thus, they took a larger part of the 100% pie. Degenerative diseases were thus correspondingly less important, because irrespective of genes or environments affecting them, we used to die of other causes.

Here is Christakis on the Anthroposphere:

NICHOLAS A. CHRISTAKIS
Physician and social scientist, Harvard

THE ANTHROPOSPHERE

...

The global population stood at one million at 10,000 BC, 50 million at 1,000 BC, and 310 million in 1,000 AD. It stood at about one billion in 1800, 1.65 billion in 1900, and 6.0 billion in 2000. Analysis of these macro-historical trends in human population usually focuses on this population growth and on the "demographic transition" underlying it.

During the first stage of the demographic transition, life—as Hobbes rightly suggested—was nasty, brutish, and short. There was a balance between birth rates and death rates, and both were very high (30-50 per thousand people per year). The human population grew less than 0.05% annually, with a doubling time of over 1,000 years. This state of affairs was true of all human populations everywhere until the late 18th century.

Then, during the second stage, the death rate began to decline—first in northwestern Europe, but then spreading over the next 100 years to the south and east. The decline in the death rate was due initially to improvements in food supply and in public health, both of which reduced mortality, particularly in childhood. As a consequence, there was a population explosion.

During the third stage, birth rates dropped for the first time in human history. The prior decline in childhood mortality probably prompted parents to realize they did not need as many children; and increasing urbanization, increasing female literacy, and (eventually) contraceptive technology also played a part.

Finally, during the fourth stage—in which the developed world presently finds itself—there is renewed stability. Birth and death rates are again in balance, but now both are relatively low. Causes of mortality have shifted from the pre-Modern pattern dominated by infectious diseases, perinatal diseases, and nutritional diseases, to one dominated by chronic diseases, mental illnesses, and behavioral conditions.

This broad story, however, conceals as much as it reveals. There are other demographic developments worldwide beyond the increasing overall size of the population, developments that are still unfolding and that matter much more. Changes in four aspects of population structure are key: (1) sex ratio, (2) age structure, (3) kinship systems, and (4) income distribution.

Sex ratios are becoming increasingly unbalanced in many parts of the world, especially in China and India (which account for 37% of the global population). The normal sex ratio at birth is roughly 106 males for every 100 females, but it may presently be as high as 120 for young people in China, or as high as 111 in India. This shift, much discussed, may arise from preferential abortion or the neglect of baby girls relative to boys. Gender imbalance may also have other determinants, such as large-scale migration of one or the other sex in search of work. This shift has numerous implications. For example, given the historical role of females as caregivers to elderly parents, a shortage of woman to fill this role will induce large-scale social adjustments. Moreover, an excess of low-status men unable to find wives results in an easy (and large) pool of recruits for extremism and violence.

This shift in gender ratios may have other, less heralded implications, however. Some of our own work has suggested that this shift may actually shorten men’s lives, reversing some of the historic progress we have made. Across a range of species, skewed sex ratios result in intensified competition for sexual partners and this induces stress for the supernumerary sex. In humans, it seems, a 5% excess of males at the time of sexual maturity shortens the survival of men by about three months in late life, which is a very substantial loss.

On the other hand, the population worldwide is getting older, especially in the developed world. Globally, the UN estimates that the proportion of people aged 60 and over will double between 2000 and 2050, from 10% to 21%, and the proportion of children will drop from 30% to 21%. This change also has numerous implications, including on the "dependency ratio," meaning that fewer young people are available to provide for the medical and economic needs of the elderly. Much less heralded, however, is the fact that war is a young person’s activity, and it is entirely likely that, as populations age, they may become less aggressive.

The changing nature of kinship networks, such as the growth in blended families—whether due to changing divorce patterns in the developed world or AIDS killing off parents in Africa—has implications for the network of obligations and entitlements within families. Changing kinship systems in modern American society (with complex mixtures of remarried and cohabiting couples, half-siblings, step-siblings, and so on) are having profound implications for caregiving, retirement, and bequests. Who cares for Grandma? Who gets her money when she dies?

Finally, it is not just the balance between males and females, or young and old, that is changing, but also the balance between rich and poor. Income inequality is reaching historic heights throughout the world. The top 1% of the people in the world receives 57% of the income. Income inequality in the US is presently at its highest recorded levels, exceeding even the Roaring Twenties. And while economic development in China has proceeded with astonishing rapidity, income is not evenly distributed; the prospects for conflict in that country as a result seem very high in the coming decades.

Lacking any real predators, a key feature of the human environment is other humans. In our rush to focus on threats such as global warming and environmental degradation, we should not overlook this fact. It is well to look around at who, and not just what, surrounds us. Population structure will change everything. Our health, wealth, and peace depend on it.

Origins of Cholera and Molecular Clock recalibration

A casual 100-fold recalibration of the molecular clock should serve as a warning not to take molecular dating too seriously, or at least to make sure to check the premises on which it is based.

PLoS ONE doi:10.1371/journal.pone.0004053

A Recalibrated Molecular Clock and Independent Origins for the Cholera Pandemic Clones

Lu Feng et al.

Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7 pandemics, but there were also local outbreaks between the 6^th (1899–1923) and 7^th (1961–present) pandemics. All the above are serotype O1, whereas environmental or invertebrate isolates are antigenically diverse. The pre 7th pandemic isolates mentioned above, and other minor pathogenic clones, are related to the 7^th pandemic clone, while the 6^th pandemic clone is in the same lineage but more distantly related, and non-pathogenic isolates show no clonal structure. To understand the origins and relationships of the pandemic clones, we sequenced the genomes of a 1937 prepandemic strain and a 6^th pandemic isolate, and compared them with the published 7^th pandemic genome. We distinguished mutational and recombinational events, and allocated these and other events, to specific branches in the evolutionary tree. There were more mutational than recombinational events, but more genes, and 44 times more base pairs, changed by recombination. We used the mutational single-nucleotide polymorphisms and known isolation dates of the prepandemic and 7^th pandemic isolates to estimate the mutation rate, and found it to be 100 fold higher than usually assumed We then used this to estimate the divergence date of the 6^th and 7^th pandemic clones to be about 1880. While there is a large margin of error, this is far more realistic than the 10,000–50,000 years ago estimated using the usual assumptions. We conclude that the 2 pandemic clones gained pandemic potential independently, and overall there were 29 insertions or deletions of one or more genes. There were also substantial changes in the major integron, attributed to gain of individual cassettes including copying from within, or loss of blocks of cassettes. The approaches used open up new avenues for analysing the origin and history of other important pathogens.

Link