Population bottlenecks and Pleistocene human evolution

We review the anatomical and archaeological evidence for anearly population bottleneck in humans and bracket the time whenit could have occurred. We outline the subsequent demographicchanges that the archaeological evidence of range expansionsand contractions address, and we examine how inbreeding effectivepopulation size provides an alternative view of past populationsize change. This addresses the question of other, more recent,population size bottlenecks, and we review nonrecombining andrecombining genetic systems that may reflect them. We examinehow these genetic data constrain the possibility of significantpopulation size bottlenecks (i.e., of sufficiently small sizeand/or long duration to minimize genetic variation in autosomaland haploid systems) at several different critical times inhuman history. Different constraints appear in nonrecombiningand recombining systems, and among the autosomal loci most areincompatible with any Pleistocene population size expansions.Microsatellite data seem to show Pleistocene population sizeexpansions, but in aggregate they are difficult to interpretbecause different microsatellite studies do not show the sameexpansion. The archaeological data are only compatible witha few of these analyses, most prominently with data from Aluelements, and we use these facts to question whether the viewof the past from analysis of inbreeding effective populationsize is valid. Finally, we examine the issue of whether inbreedingeffective population size provides any reasonable measure ofthe actual past size of the human species. We contend that ifthe evidence of a population size bottleneck early in the evolutionof our lineage is accepted, most genetic data either lack theresolution to address subsequent changes in the human populationor do not meet the assumptions required to do so validly. Itis our conclusion that, at the moment, genetic data cannot disprovea simple model of exponential population growth following abottleneck 2 MYA at the origin of our lineage and extendingthrough the Pleistocene. Archaeological and paleontologicaldata indicate that this model is too oversimplified to be anaccurate reflection of detailed population history, and thereforewe find that genetic data lack the resolution to validly reflectmany details of Pleistocene human population change. However,there is one detail that these data are sufficient to address.Both genetic and anthropological data are incompatible withthe hypothesis of a recent population size bottleneck. Suchan event would be expected to leave a significant mark acrossnumerous genetic loci and observable anatomical traits, butwhile some subsets of data are compatible with a recent populationsize bottleneck, there is no consistently expressed effect thatcan be found across the range where it should appear, and thisabsence disproves the hypothesis.     

An Australasian test of the recent African origin theory using the WLH-50 calvarium

This analysis investigates the ancestry of a single modern human specimen from Australia, WLH-50 (Thorne et al., in preparation; Webb, 1989). Evaluating its ancestry is important to our understanding of modern human origins in Australasia because the prevailing models of human origins make different predictions for the ancestry of this specimen, and others like it. Some authors believe in the validity of a complete replacement theory and propose that modern humans in Australasia descended solely from earlier modern human populations found in Late Pleistocene Africa and the Levant. These ancestral modern populations are believed to have completely replaced other archaic human populations, including the Ngandong hominids of Indonesia. According to this recent African origin theory, the archaic humans from Indonesia are classified as Homo erectus, a different evolutionary species that could not have contributed to the ancestry of modern Australasians. Therefore this theory of complete replacement makes clear predictions concerning the ancestry of the specimen WLH-50. We tested these predictions using two methods: a discriminant analysis of metric data for three samples that are potential ancestors of WLH-50 (Ngandong, Late Pleistocene Africans, Levant hominids from Skhul and Qafzeh) and a pairwise difference analysis of nonmetric data for individuals within these samples. The results of these procedures provide an unambiguous refutation of a model of complete replacement within this region, and indicate that the Ngandong hominids or a population like them may have contributed significantly to the ancestry of WLH-50. We therefore contend that Ngandong hominids should be classified within the evolutionary species, Homo sapiens. The Multiregional model of human evolution has the expectation that Australasian ancestry is in all three of the potentially ancestral groups and best explains modern Australasian origins.     

Population continuity or replacement? A novel computer simulation approach and its application to the numic expansion (Western Great Basin,USA)

In a previous study, Kaestle and Smith [Am J Phys Anthropol 115 (2001) 1-12] supported a recent (A.D. 1000) Numic expansion into the Great Basin region based on a molecular and statistical analysis of mitochondrial DNA (mtDNA) of ancient and modern native inhabitants of the region. Their statistical methodology could not rule out the possibility that observed differences in haplogroup frequencies are instead the result of long-term microevolutionary change within a single population. To distinguish more effectively between a Numic expansion versus population continuity, we employed a novel computer simulation approach that incorporates microevolutionary factors likely to affect human population genetic variation. We test whether the observed differences in haplogroup frequencies between ancient and modern Great Basin groups could have been produced solely via in situ microevolutionary change. Our results indicate that for reasonable demographic conditions, the observed genetic differences between the observed samples are consistent with population continuity if gene flow among prehistoric Great Basin local groups was less than 1% of local group size per generation. Our analysis also supports a recent population expansion if gene flow between neighboring groups exceeded 8% of local group size per generation. The simulations demonstrate that relatively low gene flow levels and random genetic drift can produce the observed degree of genetic differences between population samples. Although this study focuses on the Numic expansion, this simulation approach can be applied to any geographic region for which genetic data have been collected to address similar questions of population relationships over time.     

The impact of group fissions on genetic structure in Native South America and implications for human evolution

In a series of publications beginning in the 1960s, Neel and colleagues suggested that genetically nonrandom, or "lineal", population fissions contributed to genetic structure in ancient human groups. The authors reached this conclusion by studying the genetic consequences of village fissions among the Yanomamo, a Native South American group thought to have been relatively unaffected by European contact and, therefore, representative of the human past. On the basis of ethnographic accounts and pedigree data, they further concluded that patrilineal relationships were particularly important in shaping the genetic structure of villages following fissions. This study reexamines the genetic consequences of village fissions using autosomal STRs, Y-chromosome STRs, and mitochondrial DNA sequences collected from large samples of individuals from multiple Yanomamo villages. Our analyses of the autosomal STRs replicate the previous finding that village fissions have produced substantial genetic structure among the Yanomamo. However, our analyses of Y-chromosome STRs and mtDNA d-loop polymorphisms suggest that other population processes, including village movements, inter-village migration, and polygynous marriage, affect genetic structure in ways not predicted by a simple model of patrilineal fissions. We discuss the broader implications of population fissions for human evolution and the suitability of using the Yanomamo as a model for the human past.     

The global pattern of gene identity variation reveals a history of long-range migrations,bottlenecks, and local mate exchange: Implications for biological race

Several recent studies have argued that human genetic variation conforms to a model of isolation by distance, whereas others see a predominant role for long-range migrations and bottlenecks. It is unclear whether either of these views fully describes the global pattern of human genetic variation. In this article, we use a coalescent-based simulation approach to compare the pattern of neutral genetic variation predicted by these views to the observed pattern estimated from neutral autosomal microsatellites assayed in 1,032 individuals from 53 globally-distributed populations. We find that neither view predicts every aspect of the observed pattern of variation on its own, but that a combination of the two does. Specifically, we demonstrate that the observed pattern of global gene identity variation is consistent with a history of serial population fissions, bottlenecks and long-range migrations associated with the peopling of major geographic regions, and gene flow between local populations. This history has produced a nested pattern of genetic structure that is inconsistent with the existence of independently evolving biological races. We consider the implications of our findings for methods that apportion variation into within- and between-group components and for medical genetics. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc.     

The Effects of Socioeconomic Status,Clinical Factors,and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB susceptibility in parental populations may contribute to variation in disease susceptibility in the region.     

Rejection of a serial founder effects model of genetic and linguistic coevolution

Recent genetic studies attribute the negative correlation between population genetic diversity and distance from Africa to a serial founder effects (SFE) evolutionary process. A recent linguistic study concluded that a similar decay in phoneme inventories in human languages was also the product of the SFE process. However, the SFE process makes additional predictions for patterns of neutral genetic diversity, both within and between groups, that have not yet been tested on phonemic data. In this study, we describe these predictions and test them on linguistic and genetic samples. The linguistic sample consists of 725 widespread languages, which together contain 908 distinct phonemes. The genetic sample consists of 614 autosomal microsatellite loci in 100 widespread populations. All aspects of the genetic pattern are consistent with the predictions of SFE. In contrast, most of the predictions of SFE are violated for the phonemic data. We show that phoneme inventories provide information about recent contacts between languages. However, because phonemes change rapidly, they cannot provide information about more ancient evolutionary processes.     

Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2′-C-methyl-6-O-methyl guanosine nucleoside and l-Alanine ester phosphoramidates

7-Deazapurines are known to possess broad antiviral activity, however the 2′-C-methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus (HCV) replication. We previously reported the 6-O-methyl entity as a prodrug moiety to increase liphophilicity of guanine nucleosides and the ProTide approach applied to 2′-C-methyl-6-O-methylguanosine has lead to potent HCV inhibitors now in clinical trials. In this Letter, we report the synthesis and biological evaluation of 2′-C-methyl-6-O-methyl-7-deaza guanosine and ProTide derivatives. In contrast to prior studies, removal of the N-7 of the nucleobase entirely negates anti-HCV activity compared to the 2′-C-methyl-6-O-methylguanosine analogues. To understand better this significant loss of activity, enzymatic assays and molecular modeling were carried out and suggested 2′-C-methyl-6-O-methyl-7-deaza guanosine and related ProTides do not act as efficient prodrugs of the free nucleotide, in marked contrast to the case of the parent guanine analogue.     

Electrical Propagation of Condensed and Diffuse Ions Along Actin Filaments

Journal of Computational Neuroscience - In this article, we elucidate the roles of divalent ion condensation and highly polarized immobile water molecules on the propagation of ionic calcium waves...