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A coalescent-based estimator of admixture from DNA sequences.

A variety of estimators have been developed to use genetic marker information in inferring the admixture proportions (parental contributions) of a hybrid population. The majority of these estimators used allele frequency data, ignored molecular information that is available in markers such as microsatellites and DNA sequences, and assumed that mutations are absent since the admixture event. As a result, these estimators may fail to deliver an estimate or give rather poor estimates when admixture is ancient and thus mutations are not negligible. A previous molecular estimator based its inference of admixture proportions on the average coalescent times between pairs of genes taken from within and between populations. In this article I propose an estimator that considers the entire genealogy of all of the sampled genes and infers admixture proportions from the numbers of segregating sites in DNA sequence samples. By considering the genealogy of all sequences rather than pairs of sequences, this new estimator also allows the joint estimation of other interesting parameters in the admixture model, such as admixture time, divergence time, population size, and mutation rate. Comparative analyses of simulated data indicate that the new coalescent estimator generally yields better estimates of admixture proportions than the previous molecular estimator, especially when the parental populations are not highly differentiated. It also gives reasonably accurate estimates of other admixture parameters. A human mtDNA sequence data set was analyzed to demonstrate the method, and the analysis results are discussed and compared with those from previous studies.

Algorithms↗

Temporal scaling of molecular evolution in primates and other mammals.

Molecular clocks are routinely tested for linearity using a relative rate test and routinely calibrated against the geological time scale using a single or average paleontologically determined time of divergence between living taxa. The relative rate test is a test of parallel rate equality, not a test of rate constancy. Temporal scaling provides a test of rates, where scaling coefficients of 1.0 (isochrony) represent stochastic rate constancy. The fossil record of primates and other mammals is now known in sufficient detail to provide several independent divergence times for major taxonomic groups. Molecular difference should scale negatively or isochronically (scaling coefficients less than 1.0) with divergence time: where two or more divergence times are available, molecular difference appears to scale positively (scaling coefficient greater than 1.0). A minimum of four divergence times are required for adequate statistical power in testing the linear model: scaling is significantly nonlinear and positive in six of 11 published investigations meeting this criterion. All groups studied show some slowdown in rates of molecular change over Cenozoic time. The break from constant or increasing rates during the Mesozoic to decreasing rates during the Cenozoic appears to coincide with extraordinary diversification of placental mammals at the beginning of this era. High rates of selectively neutral molecular change may be concentrated in such discrete events of evolutionary diversification.

Amino Acid Sequence↗

A molecular timescale for vertebrate evolution.

A timescale is necessary for estimating rates of molecular and morphological change in organisms and for interpreting patterns of macroevolution and biogeography. Traditionally, these times have been obtained from the fossil record, where the earliest representatives of two lineages establish a minimum time of divergence of these lineages. The clock-like accumulation of sequence differences in some genes provides an alternative method by which the mean divergence time can be estimated. Estimates from single genes may have large statistical errors, but multiple genes can be studied to obtain a more reliable estimate of divergence time. However, until recently, the number of genes available for estimation of divergence time has been limited. Here we present divergence-time estimates for mammalian orders and major lineages of vertebrates, from an analysis of 658 nuclear genes. The molecular times agree with most early (Palaeozoic) and late (Cenozoic) fossil-based times, but indicate major gaps in the Mesozoic fossil record. At least five lineages of placental mammals arose more than 100 million years ago, and most of the modern orders seem to have diversified before the Cretaceous/Tertiary extinction of the dinosaurs.

Animals↗

Molecular drift of the bride of sevenless (boss) gene in Drosophila.

DNA sequences were determined for three to five alleles of the bride-of-sevenless (boss) gene in each of four species of Drosophila. The product of boss is a transmembrane receptor for a ligand coded by the sevenless gene that triggers differentiation of the R7 photoreceptor cell in the compound eye. Population parameters affecting the rate and pattern of molecular evolution of boss were estimated from the multinomial configurations of nucleotide polymorphisms of synonymous codons. The time of divergence between D. melanogaster and D. simulans was estimated as approximately 1 Myr, that between D. teissieri and D. yakuba as approximately 0.75 Myr, and that between the two pairs of sibling species as approximately 2 Myr. (The boss genes themselves have estimated divergence times approximately 50% greater than the species divergence times.) The effective size of the species was estimated as approximately 5 x 10(6), and the average mutation rate was estimated as 1-2 x 10(-9)/nucleotide/generation. The ratio of amino acid polymorphisms within species to fixed differences between species suggests that approximately 25% of all possible single-step amino acid replacements in the boss gene product may be selectively neutral or nearly neutral. The data also imply that random genetic drift has been responsible for virtually all of the observed differences in the portion of the boss gene analyzed among the four species.

Alcohol Dehydrogenase↗

Molecular phylogeny and biogeography of the Korean woodroaches Cryptocercus spp.

Phylogenetic relationships and biogeography of Northeast Asian Cryptocercus were inferred based on the DNA sequences of mitochondrial COII and 16S rRNA genes and nuclear 18S rRNA gene. The results suggest that two clades exist in Korean populations. The southwestern population (Cryptocercus from Jiri-san) was more closely related to the populations from Northeast China and eastern Russia than to all the other Korean Cryptocercus. According to molecular-based estimated divergence times, the divergence event occurred between Cryptocercus in Jiri-san, Northeast China and eastern Russia and those in the remaining South Korea during the Miocene (7.5-17.4Myr ago), and then the divergence event between Cryptocercus in Jiri-san and those in Northeast China and eastern Russia occurred 0.8-1.9Myr ago. In the Korean Peninsula, Jiri-san is located in the most southwestern region among the high mountains surveyed. The location is the farthest from Northeast China and eastern Russia among sampling localities in South Korea. Thus, it was unexpected that the southwestern populations are more closely related to those from Northeast China and eastern Russia rather than to the other Korean Cryptocercus. Based on Korean topography and estimated divergence times, possible scenarios are proposed for the current geographical distribution of Korean Cryptocercus.

Animals↗

Molecular evidence from the nuclear genome for the time frame of human evolution.

Evolutionary divergence times can be inferred from molecular distances if a molecular clock can be assumed and if the substitution rate can be estimated. We present new evidence from relative rate tests that the rate of substitution at fourfold degenerate sites of nuclear genome-coding DNA is uniform in primate and rodent lineages. We also review recent relative rate test results showing substitution rate uniformity in the nuclear genome of simian primates. DNA distances between a range of mammalian taxa shows that a molecular clock is inconsistent with many assumed divergence times irrespective of the assumed substitution rate. We find that the substitution rate that implies the best compromise fit with divergence times across the range of taxa is 2.0-2.25 x 10(-9). This range of substitution rates implies a divergence time of humans and chimpanzees of 4.0-3.6 million years ago. This postdates the occurrence of Ardipithecus ramidus and the earliest occurrence of Australopithecus afarensis, suggesting that the common ancestor of humans and chimpanzees was bipedal and that the trait has been lost in chimpanzees rather than gained in humans.

Animals↗

Tempo and mode of sequence evolution in mitochondrial DNA of Hawaiian Drosophila.

Sequence comparisons were made for up to 667 bp of DNA cloned from 14 kinds of Hawaiian Drosophila and five other dipteran species. These sequences include parts of the genes for NADH dehydrogenase (subunits 1, 2, and 5) and rRNA (from the large ribosomal subunit). Because the times of divergence among these species are known approximately, the sequence comparisons give insight into the evolutionary dynamics of this molecule. Transitions account for nearly all of the differences between sequences that have diverged by less than 2%: for these sequences the mean rate of divergence appears to be about 2%/Myr. In comparisons involving greater divergence times and greater sequence divergence, relatively more of the sequence differences are due to transversions. Specifically, the fraction of these differences that are counted as transversions rises from an initial value of less than 0.1 to a plateau value of nearly 0.6. The time required to reach half of the plateau value, about 10 Myr, is similar to that for mammalian mtDNA. The mtDNAs of flies and mammals are also alike in the shape of the curve relating the percentage of positions at which there are differences in protein-coding regions to the time of divergence. For both groups of animals, the curve has a steep initial slope ascribable to fast accumulation of synonymous substitutions and a shallow final slope resulting from the slow accumulation of substitutions causing amino acid replacements. However, the percentage of all sites that can experience a high rate of substitution appears to be only about 8% for fly mtDNA compared to about 20% for mammalian mtDNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Length and time scale divergences at the magnetization-reversal transition in the Ising model.

The divergences of both the length and time scales, at the magnetization-reversal transition in the Ising model under a pulsed field, have been studied in the linearized limit of the mean field theory. Both the length and time scales are shown to diverge at the transition point and it has been checked that the nature of the time scale divergence agrees well with the result obtained from the numerical solution of the mean field equation of motion. Similar growths in length and time scales are also observed, as one approaches the transition point, using Monte Carlo simulations. However, these are not of the same nature as the mean field case. Nucleation theory provides a qualitative argument that explains the nature of the time scale growth. To study the nature of growth of the characteristic length scale, we have looked at the cluster size distribution of the reversed spin domains and have defined a pseudocorrelation length that has been observed to grow at the phase boundary of the transition.

Journal Article↗

Human and ape molecular clocks and constraints on paleontological hypotheses.

Although the relationships of the living hominoid primates (humans and apes) are well known, the relationships of the fossil species, times of divergence of both living and fossil species, and the biogeographic history of hominoids are not well established. Divergence times of living species, estimated from molecular clocks, have the potential to constrain hypotheses of the relationships of fossil species. In this study, new DNA sequences from nine protein-coding nuclear genes in great apes are added to existing datasets to increase the precision of molecular time estimates bearing on the evolutionary history of apes and humans. The divergence of Old World monkeys and hominoids at the Oligocene-Miocene boundary (approximately 23 million years ago) provides the best primate calibration point and yields a time and 95% confidence interval of 5.4 +/- 1.1 million years ago (36 nuclear genes) for the human-chimpanzee divergence. Older splitting events are estimated as 6.4 +/- 1.5 million years ago (gorilla, 31 genes), 11.3 +/- 1.3 million years ago (orangutan, 33 genes), and 14.9 +/- 2.0 million years ago (gibbon, 27 genes). Based on these molecular constraints, we find that several proposed phylogenies of fossil hominoid taxa are unlikely to be correct.

Animals↗

The influence of selection on the evolutionary distance estimated from the base changes observed between homologous nucleotide sequences.

In most studies of molecular evolution, the nucleotide base at a site is assumed to change with the apparent rate under functional constraint, and the comparison of base changes between homologous genes is thought to yield the evolutionary distance corresponding to the site-average change rate multiplied by the divergence time. However, this view is not sufficiently successful in estimating the divergence time of species, but mostly results in the construction of tree topology without a time-scale. In the present paper, this problem is investigated theoretically by considering that observed base changes are the results of comparing the survivals through selection of mutated bases. In the case of weak selection, the time course of base changes due to mutation and selection can be obtained analytically, leading to a theoretical equation showing how the selection has influence on the evolutionary distance estimated from the enumeration of base changes. This result provides a new method for estimating the divergence time more accurately from the observed base changes by evaluating both the strength of selection and the mutation rate. The validity of this method is verified by analysing the base changes observed at the third codon positions of amino acid residues with four-fold codon degeneracy in the protein genes of mammalian mitochondria; i.e. the ratios of estimated divergence times are fairly well consistent with a series of fossil records of mammals. Throughout this analysis, it is also suggested that the mutation rates in mitochondrial genomes are almost the same in different lineages of mammals and that the lineage-specific base-change rates indicated previously are due to the selection probably arising from the preference of transfer RNAs to codons.

Animals↗

Molecular evolution of the arthropod hemocyanin superfamily.

Arthropod hemocyanins are members of a protein superfamily that also comprises the arthropod phenoloxidases (tyrosinases), crustacean pseudohemocyanins (cryptocyanins), and insect storage hexamerins. The evolution of these proteins was inferred by neighbor-joining, maximum-parsimony, and maximum-likelihood methods. Monte Carlo shuffling approaches provided evidence against a discernible relationship of the arthropod hemocyanin superfamily and molluscan hemocyanins or nonarthropodan tyrosinases. Within the arthropod hemocyanin superfamily, the phenoloxidase probably emerged early in the (eu-)arthropod stemline and thus form the most likely outgroup. The respiratory hemocyanins evolved from these enzymes before the radiation of the extant euarthropodan subphyla. Due to different functional constraints, replacement rates greatly vary between the clades. Divergence times were thus estimated assuming local molecular clocks using several substitution models. The results were consistent and indicated the separation of the cheliceratan and crustacean hemocyanins close to 600 MYA. The different subunit types of the multihexameric cheliceratan hemocyanin have a rather conservative structure and diversified in the arachnidan stemline between 550 and 450 MYA. By contrast, the separation of the crustacean (malacostracan) hemocyanin subunits probably occurred only about 200 MYA. The nonrespiratory pseudohemocyanins evolved within the Decapoda about 215 MYA. The insect hemocyanins and storage hexamerins emerged independently from the crustacean hemocyanins. The time of divergence of the insect proteins from the malacostracan hemocyanins was estimated to be about 430-440 MYA, providing support for the notion that the Hexapoda evolved from the same crustacean lineage as the Malacostraca.

Animals↗

Coalescent-based hypothesis testing supports multiple Pleistocene refugia in the Pacific Northwest for the Pacific giant salamander (Dicamptodon tenebrosus).

Phylogeographic patterns of many taxa are explained by Pleistocene glaciation. The temperate rainforests within the Pacific Northwest of North America provide an excellent example of this phenomenon, and competing phylogenetic hypotheses exist regarding the number of Pleistocene refugia influencing genetic variation of endemic organisms. One such endemic is the Pacific giant salamander, Dicamptodon tenebrosus. In this study, we estimate this species' phylogeny and use a coalescent modeling approach to test five hypotheses concerning the number, location and divergence times of purported Pleistocene refugia. Single refugium hypotheses include: a northern refugium in the Columbia River Valley and a southern refugium in the Klamath-Siskiyou Mountains. Dual refugia hypotheses include these same refugia but separated at varying times: last glacial maximum (20,000 years ago), mid-Pleistocene (800,000 years ago) and early Pleistocene (1.7 million years ago). Phylogenetic analyses and inferences from nested clade analysis reveal distinct northern and southern lineages expanding from the Columbia River Valley and the Klamath-Siskiyou Mountains, respectively. Results of coalescent simulations reject both single refugium hypotheses and the hypothesis of dual refugia with a separation date in the late Pleistocene but not hypotheses predicting dual refugia with separation in early or mid-Pleistocene. Estimates of time since divergence between northern and southern lineages also indicate separation since early to mid-Pleistocene. Tests for expanding populations using mismatch distributions and 'g' distributions reveal demographic growth in the northern and southern lineages. The combination of these results provides strong evidence that this species was restricted into, and subsequently expanded from, at least two Pleistocene refugia in the Pacific Northwest.

Animals↗

Monophyly and relationships of the tribe Exaceae (Gentianaceae) inferred from nuclear ribosomal and chloroplast DNA sequences.

Both chloroplast trnL (UAA) intron and nuclear ribosomal ITS sequences highly confirmed the monophyly of the tribes of the Gentianaceae defined by the recent classification, and revealed the tribe Exaceae as a basal clade just next to the basal-most lineage, the tribe Saccifolieae. Within the tribe Exaceae, Sebaea (except Sebaea madagascariensis) appeared as the most basal clade as the sister group to the rest of the tribe. The Madagascan endemic genera Gentianothamnus and Tachiadenus were very closely related to each other, together standing as sister to a clade comprising Sebaea madagascariensis, Ornichia, and Exacum. The saprophytic genus Cotylanthera nested deeply inside Exacum. Sebaea madagascariensis was shown closer to the Madagascan endemic genus Ornichia than to any other sampled Sebaea species. Exacum appeared as the most derived taxon within this tribe. The topology of the phylogenetic trees conform with the Gondwana vicariance hypothesis regarding the biogeography of Exaceae. However, no evidence for matching the older relationships within the family to the tectonic history could be corroborated with various divergence time analyses. Divergence dating estimated a post-Gondwana diverging of the Gentianaceae about 50 million years ago (MYA), and the tribe Exaceae as about 40 MYA. The Mozambique Channel land-bridge could have played an important role in the biogeographic history of the tribe Exaceae.

Africa↗

Nucleotide sequence analysis of Adh genes estimates the time of geographic isolation of the Bogota population of Drosophila pseudoobscura.

The population of Drosophila pseudoobscura at Bogota, Columbia, is geographically and partially reproductively isolated from populations in the main body of the species in North America. The degree of genetic differentiation and time of divergence between populations at Bogota and Apple Hill, CA, were estimated by comparison of 3388 nucleotides in the alcohol dehydrogenase region (Adh and Adh-Dup genes) of 18 strains. Of the 146 polymorphic nucleotide sites detected, 68 and 31 were unique to the Apple Hill and Bogota samples, respectively, and 53 were shared. On the basis of an observed net divergence per nucleotide site of 0.264% between the two samples, the Bogota and North American populations were estimated to have been separated for at least 155,000 years. This divergence time suggests that D. pseudoobscura extended its range from North America to South America in a period of Pleistocene glaciation, when habitat suitable for the species presumably existed in lowland Central America.

Alcohol Dehydrogenase↗

Genetic variation within and among three Indian breeds of goat using heterologous microsatellite markers.

The parameters of genetic variation, genetic distances and time of divergence in three Indian goat breeds were studied using 16 cattle microsatellite markers. The mean number of alleles and mean allele size (bp) per microsatellite marker in goats were 5.37 +/- 0.78 and 143.9 +/- 33.75 bp respectively. The average values of heterozygosity and polymorphism information content were 0.54 +/- 0.2 and 0.48 +/- 0.20, respectively. Five of the eight genetic distance methods were highly correlated, revealing a closer relationship between Jamnapari and Barbari goats. A phylogenetic tree constructed from inter-individual distances revealed that the individuals clustered according to the breed to which they belonged, and the Jamnapari and Barbari goats formed a cluster. The divergence times between Sirohi and Jamnapari, and Sirohi and Barbari were approximately 2000 years, while its value between Barbari and Jamnapari goats was approximately 1370 years.

Animals↗

Analysis of conserved microsatellite sequences suggests closer relationship between water buffalo Bubalus bubalis and sheep Ovis aries.

The distribution and evolutionary pattern of the conserved microsatellite repeat sequences (CA)n, (TGG)6, and (GGAT)4 were studied to determine the divergence time and phylogenetic position of the water buffalo, Bubalus bubalis. The mean allelic frequencies of these repeat loci showed a high level of heterozygosity among the euartiodactyls (buffalo, cattle, sheep, and goat). Genetic distances calculated from the allelic frequencies of these microsatellites were used to position Bubalus bubalis in the phylogenetic tree. The tree topology revealed a closer proximity of the Bubalus bubalis to the Ovis aries (sheep) genome than to other domestic species. The estimated time of divergence of the water buffalo genome relative to cattle, goat, sheep, pig, rabbit, and horse was found to be 21, 0.5, 0.7, 94, 20.3, and 408 million years (Myr), respectively. Although water buffaloes share morphological and biochemical similarities with cattle, our study using the microsatellite sequences places the bubaline species in an entirely new phylogenetic position. Our results also suggest that with respect to these repeat loci, the water buffalo genome shares a common ancestry with sheep and goat after the divergence of subfamily Bovinae (Bos taurus) from the family Bovidae.

Animals↗

Dynamics of repeat polymorphisms under a forward-backward mutation model: within- and between-population variability at microsatellite loci.

Suggested molecular mechanisms for the generation of new tandem repeats of simple sequences indicate that the microsatellite loci evolve via some of forward-backward mutation. We provide a mathematical basis for suggesting a measure of genetic distance between populations based on microsatellite variation. Our results indicate that such a genetic distance measure can remain proportional to the divergence time of populations even when the forward-backward mutations produce variable and/or directionally biased alleles size changes. If the population size and the rate of mutation remain constant, then the measure will be proportional to the time of divergence of populations. This genetic distance is expressed in terms of a ratio of components of variance of allele sizes, based on expressions developed for studying population dynamics of quantitative traits. Application of this measure to data on 18 microsatellite loci in the nine human populations leads to evolutionary trees consistent with the known ethnohistory of the populations.

Alleles↗

Phylogenetic and virulence analysis of tick-borne encephalitis viruses from Japan and far-Eastern Russia.

We have previously reported that tick-borne encephalitis (TBE) is endemic in a specific area of Hokkaido, Japan. In Oshima, the southern part of Hokkaido, TBE virus was isolated from sentinel dogs, ticks and rodents in 1995 and 1996. To identify when these TBE viruses emerged in Hokkaido, the times of divergence of TBE virus strains isolated in Oshima and far-eastern Russia were estimated. TBE virus was isolated in Khabarovsk in 1998 and the nucleotide sequences of viral envelope protein genes of isolates from Oshima and Khabarovsk were compared. From the synonymous substitution rate of these virus strains, the lineage divergence time of these TBE virus strains was predicted phylogenetically to be about 260-430 years ago. Furthermore, the virulence of TBE virus isolates from Oshima and Khabarovsk were compared in a mouse model. The results showed that the isolates possessed very similar virulence in mice. This report provides evidence that the Oshima strains of TBE virus in Hokkaido emerged from far-eastern Russia a few hundred years ago and this explains why these strains possess virulence similar to the TBE viruses isolated in Russia.

Amino Acid Sequence↗