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Biomedical subjects

M Stoneking

Publications and source records attributed to M Stoneking.

At least 73 records · Page 4Linked to original sources
PubMed1996

Nonneutral mitochondrial DNA variation in humans and chimpanzees.

We sequenced the NADH dehydrogenase subunit 3 (ND3) gene from a sample of 61 humans, five common chimpanzees, and one gorilla to test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution. Within humans and within chimpanzees, the ratio of replacement to silent nucleotide substitutions was higher than observed in comparisons between species, contrary to neutral expectations. To test the generality of this result, we reanalyzed published human RFLP data from the entire mitochondrial genome. Gains of restriction sites relative to a known human mtDNA sequence were used to infer unambiguous nucleotide substitutions. We also compared the complete mtDNA sequences of three humans. Both the RFLP data and the sequence data reveal a higher ratio of replacement to silent nucleotide substitutions within humans than is seen between species. This pattern is observed at most or all human mitochondrial genes and is inconsistent with a strictly neutral model. These data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases.

Amino Acid Sequence↗
PubMed1996

mtDNA control-region sequence variation suggests multiple independent origins of an "Asian-specific" 9-bp deletion in sub-Saharan Africans.

The intergenic COII/tRNA(Lys) 9-bp deletion in human mtDNA, which is found at varying frequencies in Asia, Southeast Asia, Polynesia, and the New World, was also found in 81 of 919 sub-Saharan Africans. Using mtDNA control-region sequence data from a subset of 41 individuals with the deletion, we identified 22 unique mtDNA types associated with the deletion in Africa. A comparison of the unique mtDNA types from sub-Saharan Africans and Asians with the 9-bp deletion revealed that sub-Saharan Africans and Asians have sequence profiles that differ in the locations and frequencies of variant sites. Both phylogenetic and mismatch-distribution analysis suggest that 9-bp deletion arose independently in sub-Saharan Africa and Asia and that the deletion has arisen more than once in Africa. Within Africa, the deletion was not found among Khoisan peoples and was rare to absent in western and southwestern African populations, but it did occur in Pygmy and Negroid populations from central Africa and in Malawi and southern African Bantu-speakers. The distribution of the 9-bp deletion in Africa suggests that the deletion could have arisen in central Africa and was then introduced to southern Africa via the recent "Bantu expansion."

Africa South of the Sahara↗
PubMed1996

Extent of heterogeneity in mitochondrial DNA of ethnic Asian populations.

Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence-specific oligonucleotide (SSO) probes is described for 993 individuals in 11 ethnic Asian populations. Estimates of diversity for mtDNA types exceed 0.94 in all populations, while 53% of the 255 types that were observed occur only once. Of 96 shared types, four occur at frequencies of greater than 10% but less than 17% in any one population. There is statistically significant heterogeneity among these 11 populations, however, an analysis of variance incorporating genetic distances between types shows that at least 95% of the variation present in the total sample is attributable to within-population diversity, while only 5% is due to between-population differences. Overall, heterogeneity with respect to mtDNA SSO types is grossly correlated with geographic distance between populations; the most extreme heterogeneity was observed between populations from East Asia and populations from West Asia. With respect to population genetics, the control region of mtDNA exhibits satisfactory qualities as a DNA typing locus.

Analysis of Variance↗
PubMed1996

Novel mitochondrial DNA insertion polymorphism and its usefulness for human population studies.

The frequency of a polymorphic mitochondrial DNA insertion into the nuclear genome was determined for 870 individuals from a geographically diverse set of 20 populations. The mtDNA insertion frequency varies significantly among populations, having a large GST value (0.178) and high heterozygosity values within populations. The clinal pattern of increasing frequency of the insertion from Africans through Europeans and Asians to native Americans is striking. The polymorphism is a new example of insertion-deletion polymorphisms and is a valuable marker for human population and evolutionary studies.

Base Sequence↗
PubMed1995

Polymorphic human specific Alu insertions as markers for human identification.

Alu sequences represent the largest family of short interspersed repetitive elements (SINEs) in humans with 500 000 copies per genome. Recently, one Alu subfamily was found to be human specific (HS). We originally described the use of polymorphis HS Alu insertions as a tool in population studies and recently as tools in DNA fingerprinting and forensic analysis. In this report, we will use this simple polymerase chain reaction (PCR) base technique for the detection of HS Alu insertion polymorphisms. We will test the resolving power of this DNA profiling approach in both population genetics and paternity assessment. At the population level, we will describe the genotypic distribution of five polymorphic Alu insertions among 3 populations from the American continent, one of African origin, the other two Amerindians. Insight into their relationships will be provided. At the family level, we will examine one European American family of seven individuals and the same pedigree will also be characterized by way of the two systems currently and widely used to ascertain paternity: PCR-sequence specific oligonucleotide probe hybridization (PCR-SSO) and PCR-restriction fragment length polymorphism (PCR-RFLP) of human leucocyte antigen (HLA) class II molecules, and a standard RFLP protocol used in forensic casework and paternity studies. The importance and strengths of the methods as well as its perspectives for future use in filiation studies will be evaluated.

Forensic Medicine↗
PubMed1995

Evolutionary history of the COII/tRNALys intergenic 9 base pair deletion in human mitochondrial DNAs from the Pacific.

Length changes in human mitochondrial DNA (mtDNA) are potentially useful markers for inferring the evolutionary history of populations. One such length change is a nine base pair (9-bp) deletion that is located in the intergenic region between the COII gene and the Lysine tRNA gene (COII/tRNALys intergenic region). This deletion has been used as a genetic marker to trace descent from peoples of East Asian origin. A geographic cline of the deletion frequency across modern Pacific Islander populations suggests that the deletion may be useful for tracing prehistoric Polynesian origins and affinities. Mitochondrial DNA sequence variation within two variable segments of the control region (CR) permits a number of inferences regarding the evolutionary history of the 9-bp deletion that cannot be determined from frequency data alone. We obtained CR sequences from 74 mtDNAs with the 9-bp deletion from Indonesia, coastal Papua New Guinea (PNG), and American Samoa. Phylogenetic and pairwise distribution analysis of these CR sequences pooled with previously published CR sequences reveals that the deletion arose independently in Africa and Asia and suggests possible multiple origins of the deletion in Asia. A clinal increase of the frequency of the 9-bp deletion across the three Pacific populations is associated with a decrease in CR sequence diversity, consistent with founder events. Furthermore, analysis of pairwise difference distributions indicates an expansion time of proto-Polynesians that began 5,500 yr ago from Southeast Asia. These results are consistent with the express train model of Polynesian origins.

Base Sequence↗
PubMed1995

Polynesian genetic affinities with Southeast Asian populations as identified by mtDNA analysis.

Polynesian genetic affinities to populations of Asia were studied using mtDNA markers. A total of 1,037 individuals from 12 populations were screened for a 9-bp deletion in the intergenic region between the COII and tRNA(Lys) genes that approaches fixation in Polynesians. Sequence-specific oligonucleotide probes that identify specific mtDNA control region nucleotide substitutions were used to describe variation in individuals with the 9-bp deletion. The 9-bp deletion was not observed in northern Indians, Bangladeshis, or Pakistanis but was seen at low to moderate frequencies in the nine other Southeast Asian populations. Three substitutions in the control region at positions 16217, 16247, and 16261 have previously been observed at high frequency in Polynesian mtDNAs; this "Polynesian motif" was observed in 20% of east Indonesians with the 9-bp deletion but was observed in only one additional individual. mtDNA types related to the Polynesian motif are highest in frequency in the corridor from Taiwan south through the Philippines and east Indonesia, and the highest diversity for these types is in Taiwan. These results are consistent with linguistic evidence of a Taiwanese origin for the proto-Polynesian expansion, which spread throughout Oceania by way of Indonesia.

Asia, Southeastern↗
PubMed1994

African origin of human-specific polymorphic Alu insertions.

Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu element at a particular locus. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay that uses primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution.

Africa↗
PubMed1994

Mitochondrial DNA and human evolution.

For the past seven years or so, much discussion and controversy in the field of human evolution has revolved around the application and interpretation of studies of human mitochondrial DNA variation, particularly the hypothesis that all mtDNA types in contemporary populations can be traced back to a single African ancestor who lived about 200,000 years ago. In this review I describe the evidence that led to this hypothesis, subsequent work, and where things stand now, particularly with respect to recent criticisms concerning the adequacy of phylogenetic analyses of the mtDNA data. I also describe a new method of analyzing mtDNA data that suggests that all human populations underwent a dramatic expansion some 40,000 years ago, possibly in association with revolutionary advances in human behavior, as well as an important implication of population expansions for mtDNA disease studies.

Africa↗
PubMed1994

Assessing ethnicity from human mitochondrial DNA types determined by hybridization with sequence-specific oligonucleotides.

A logistic regression model was developed to predict ethnic group from mitochondrial DNA (mtDNA) types determined by hybridization with sequence-specific oligonucleotide (SSO) probes of the two hypervariable segments of the mtDNA control region. The model was developed with, and tested against, a previously reported data set of 525 individuals from five ethnic groups (African-American, Southeast Asian, Caucasian, Japanese, and Mexican) involving 23 probes at nine regions within the two hypervariable segments [1]. The model correctly predicted the ethnic group of 65.3% of the overall sample; however, the success rate varied substantially among ethnic groups, with the most success obtained with Caucasians (81% correctly classified). A discriminant analysis yielded similar results. An example is given of using the model to predict the ethnic group of an SSO-type from a forensic case. Such models provide alternatives to traditional skeletal-based methods of predicting ethnicity, especially in cases where skeletal material is absent or incomplete.

Asian↗
PubMed1994

Mismatch distributions of mtDNA reveal recent human population expansions.

Although many genetic studies of human evolution have tried to make distinctions between the replacement and the multiregional evolution hypotheses, current methods and data have not resolved the issue. However, new advances in nucleotide divergence theory can complement these investigations with a description of human demographic behavior during the late Middle and Upper Paleolithic (approximately the last 250,000 years). Restriction fragment length polymorphism (RFLP) and DNA sequence analyses of human mitochondrial DNAs (mtDNAs) from 25 ethnic and racial groups indicate that significant expansions occurred during the late Middle and Upper Paleolithic in 23 of the 25 populations examined. Estimates for the individual group expansion times are consistently less than 100,000 years ago with a mean expansion time of approximately 40,000 years ago. The dramatic expansions suggested by these data occurred well after modern human anatomy appeared, approximately 100,000 years ago, but are concordant with archeological evidence for the expansion of modern human technology, approximately 50,000 years ago.

Base Sequence↗
PubMed1994

Optimizing utilization of DNA from rare or archival anthropological samples.

There is widespread interest in obtaining genetic samples from human populations worldwide for various studies of human genetic diversity. Many samples exist today only in the form of small, rare, irreplaceable, or archival samples, such as material from ancient bone, hair bulbs, or remnants of samples collected in the field decades ago for the purpose of protein and blood type analysis. Here, we describe the application of an approach to amplify DNA, which we call adapter attachment and amplification (AAA). This approach is useful for amplifying the genome in a reasonably representative way from small amounts of starting material using standard PCR-based methods. We apply a version of these methods to DNA extracted from washed red blood cells collected in the 1960s and 1970s in the Amazon basin. AAA and similar approaches may make the analysis of archival samples possible without exhausting that irreplaceable material and may lead to greatly improved efficiency in collecting and using new anthropological genetic samples.

Anthropology↗