A genetic legacy from archaic Homo.

The roles of fossil human populations in the origin of modern humans have been enigmatic. Earlier (archaic) human populations were biologically similar and were in recurrent temporal and geographic contact, making interbreeding between ancient populations likely. Regardless of the taxonomic status of these populations, adaptive alleles may have introgressed from archaic populations into modern humans. When an introgressed archaic allele has a selective advantage, even rare interbreeding can lead to its spread or fixation in later human populations. Several genetic loci are candidates for such introgression, including microcephalin, a gene influencing brain development. This example may suggest that the evolution of human cognition depended in part on the genetic legacy of archaic groups such as the Neanderthals.

Detecting positive selection from genome scans of linkage disequilibrium.

BACKGROUND: Though a variety of linkage disequilibrium tests have recently been introduced to measure the signal of recent positive selection, the statistical properties of the various methods have not been directly compared. While most applications of these tests have suggested that positive selection has played an important role in recent human history, the results of these tests have varied dramatically. RESULTS: Here, we evaluate the performance of three statistics designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To analyze the properties of these tests, we introduce a new computational method that can model complex population histories with migration and changing population sizes to simulate gene trees influenced by recent positive selection. We demonstrate that iHS performs substantially better than the other two statistics, with power of up to 0.74 at the 0.01 level for the variation best suited for full genome scans and a power of over 0.8 at the 0.01 level for the variation best suited for candidate gene tests. The performance of the iHS statistic was robust to complex demographic histories and variable recombination rates. Genome scans involving the other two statistics suffer from low power and high false positive rates, with false discovery rates of up to 0.96 for ALnLH. The difference in performance between iHS and ALnLH, did not result from the properties of the statistics, but instead from the different methods for mitigating the multiple comparison problem inherent in full genome scans. CONCLUSIONS: We introduce a new method for simulating genealogies influenced by positive selection with complex demographic scenarios. In a power analysis based on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective sweeps. We also show that the single-site iHS statistic is more powerful in a candidate gene test than the multi-site statistic, but that the multi-site statistic maintains a low false discovery rate with only a minor loss of power when applied to a scan of the entire genome. Our results highlight the need for careful consideration of multiple comparison problems when evaluating and interpreting the results of full genome scans for positive selection.

Recent acceleration of human adaptive evolution.

Genomic surveys in humans identify a large amount of recent positive selection. Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated greatly during the last 40,000 years. We tested the null hypothesis that the observed age distribution of recent positively selected linkage blocks is consistent with a constant rate of adaptive substitution during human evolution. We show that a constant rate high enough to explain the number of recently selected variants would predict (i) site heterozygosity at least 10-fold lower than is observed in humans, (ii) a strong relationship of heterozygosity and local recombination rate, which is not observed in humans, (iii) an implausibly high number of adaptive substitutions between humans and chimpanzees, and (iv) nearly 100 times the observed number of high-frequency linkage disequilibrium blocks. Larger populations generate more new selected mutations, and we show the consistency of the observed data with the historical pattern of human population growth. We consider human demographic growth to be linked with past changes in human cultures and ecologies. Both processes have contributed to the extraordinarily rapid recent genetic evolution of our species.

Culture creates genetic structure in the Caucasus: autosomal, mitochondrial, and Y-chromosomal variation in Daghestan.

BACKGROUND: Near the junction of three major continents, the Caucasus region has been an important thoroughfare for human migration. While the Caucasus Mountains have diverted human traffic to the few lowland regions that provide a gateway from north to south between the Caspian and Black Seas, highland populations have been isolated by their remote geographic location and their practice of patrilocal endogamy. We investigate how these cultural and historical differences between highland and lowland populations have affected patterns of genetic diversity. We test 1) whether the highland practice of patrilocal endogamy has generated sex-specific population relationships, and 2) whether the history of migration and military conquest associated with the lowland populations has left Central Asian genes in the Caucasus, by comparing genetic diversity and pairwise population relationships between Daghestani populations and reference populations throughout Europe and Asia for autosomal, mitochondrial, and Y-chromosomal markers. RESULTS: We found that the highland Daghestani populations had contrasting histories for the mitochondrial DNA and Y-chromosome data sets. Y-chromosomal haplogroup diversity was reduced among highland Daghestani populations when compared to other populations and to highland Daghestani mitochondrial DNA haplogroup diversity. Lowland Daghestani populations showed Turkish and Central Asian affinities for both mitochondrial and Y-chromosomal data sets. Autosomal population histories are strongly correlated to the pattern observed for the mitochondrial DNA data set, while the correlation between the mitochondrial DNA and Y-chromosome distance matrices was weak and not significant. CONCLUSION: The reduced Y-chromosomal diversity exhibited by highland Daghestani populations is consistent with genetic drift caused by patrilocal endogamy. Mitochondrial and Y-chromosomal phylogeographic comparisons indicate a common Near Eastern origin of highland populations. Lowland Daghestani populations show varying influence from Near Eastern and Central Asian populations.

Western Europe, state formation, and genetic pacification.

Through its monopoly on violence, the State tends to pacify social relations. Such pacification proceeded slowly in Western Europe between the 5th and 11th centuries, being hindered by the rudimentary nature of law enforcement, the belief in a man's right to settle personal disputes as he saw fit, and the Church's opposition to the death penalty. These hindrances began to dissolve in the 11th century with a consensus by Church and State that the wicked should be punished so that the good may live in peace. Courts imposed the death penalty more and more often and, by the late Middle Ages, were condemning to death between 0.5 and 1.0% of all men of each generation, with perhaps just as many offenders dying at the scene of the crime or in prison while awaiting trial. Meanwhile, the homicide rate plummeted from the 14th century to the 20th. The pool of violent men dried up until most murders occurred under conditions of jealousy, intoxication, or extreme stress. The decline in personal violence is usually attributed to harsher punishment and the longer-term effects of cultural conditioning. It may also be, however, that this new cultural environment selected against propensities for violence.

MIGRATION AND GENETIC DRIFT IN HUMAN POPULATIONS.

In humans and many other species, mortality is concentrated early in the life cycle, and is low during the ages of dispersal and reproduction. Yet precisely the opposite is assumed by classical population-genetics models of migration and genetic drift. We introduce a model in which population regulation occurs before migration. In contrast to the conventional model, our model implies that geographic variation in the allele frequencies of newborns should exceed that of adults. Thus, it is important to distinguish genetic variation of adults from that of newborns in species with human-like life cycles. Classical models deal with the variance of group allele frequencies about the allele frequency of a hypothetical "continent" or "foundation stock." Empirical studies, however, can only measure "reduced" variance, i.e., variance about the current population mean. Our model deals with reduced variance, and should therefore be more relevant to field studies. We show that reduced variance converges faster, which implies that populations are more likely to be at equilibrium with respect to reduced than unreduced variance. To summarize the effect of migration on genetic population structure, we introduce a new parameter, the effective migration rate. Unlike most population structure statistics, it does not confound the effects of mobility and population size, and it should therefore be useful for comparisons between populations. Finally, we show that the difference between geographic variation of newborn and adult allele frequencies contains information about both effective population size and effective migration rate.

Sequence variations in the public human genome data reflect a bottlenecked population history.

Single-nucleotide polymorphisms (SNPs) constitute the great majority of variations in the human genome, and as heritable variable landmarks they are useful markers for disease mapping and resolving population structure. Redundant coverage in overlaps of large-insert genomic clones, sequenced as part of the Human Genome Project, comprises a quarter of the genome, and it is representative in terms of base compositional and functional sequence features. We mined these regions to produce 500,000 high-confidence SNP candidates as a uniform resource for describing nucleotide diversity and its regional variation within the genome. Distributions of marker density observed at different overlap length scales under a model of recombination and population size change show that the history of the population represented by the public genome sequence is one of collapse followed by a recent phase of mild size recovery. The inferred times of collapse and recovery are Upper Paleolithic, in agreement with archaeological evidence of the initial modern human colonization of Europe.