CiteULike: usagi-kirin's library [128 articles]

Effects of linkage on rates of molecular evolution.

CW Birky — 2008-05-19T13:20:39-00:00

Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 17. (September 1988), pp. 6414-6418.

When an advantageous mutation is fixed in a population by selection, a closely linked selectively neutral or mildly detrimental mutation may "hitchhike" to fixation along with it. It has been suggested that hitchhiking might increase the rate of molecular evolution. Computer simulations and a mathematical argument show that complete linkage to either advantageous or deleterious mutations does not affect the substitution of selectively neutral mutations. However, the simulations show that linkage to selected background mutations decreases the rate of fixation of advantageous mutations and increases the rate of fixation of detrimental mutations. This is true whether the linked background mutations are advantageous or detrimental, and it verifies and extends previous observations that linkage tends to reduce the effects of selection on evolution. These results can be interpreted in terms of the Hill-Robertson effect: a locus linked to another locus under selection experiences a reduction in effective population size. The interpretation of differences in evolutionary rates between different genomes or different regions of a genome may be confounded by the effects of strong linkage and selection. Recombination is expected to reduce the overall rate of molecular evolution while enhancing the rate of adaptive evolution.

Mitochondrial DNA evolution in the genus Equus.

M George — 2008-05-12T19:46:21-00:00

Molecular biology and evolution, Vol. 3, No. 6. (November 1986), pp. 535-546.

Employing mitochondrial DNA (mtDNA) restriction-endonuclease maps as the basis of comparison, we have investigated the evolutionary affinities of the seven species generally recognized as the genus Equus. Individual species' cleavage maps contained an average of 60 cleavage sites for 16 enzymes, of which 29 were invariant for all species. Based on an average divergence rate of 2%/Myr, the variation between species supports a divergence of extant lineages from a common ancestor approximately 3.9 Myr before the present. Comparisons of cleavage maps between Equus przewalskii (Mongolian wild horse) and E. caballus (domestic horse) yielded estimates of nucleotide sequence divergence ranging from 0.27% to 0.41%. This range was due to intraspecific variation, which was noted only for E. caballus. For pairwise comparisons within this family, estimates of sequence divergence ranged from 0% (E. hemionus onager vs. E. h. kulan) to 7.8% (E. przewalskii vs. E. h. onager). Trees constructed according to the parsimony principle, on the basis of 31 phylogenetically informative restriction sites, indicate that the three extant zebra species represent a monophyletic group with E. grevyi and E. burchelli antiquorum diverging most recently. The phylogenetic relationships of E. africanus and E. hemionus remain enigmatic on the basis of the mtDNA analysis, although a recent divergence is unsupported.

Mitochondrial control region and 12S rRNA variation in Przewalski's horse (Equus przewalskii).

EA Oakenfull — 2008-05-12T19:27:58-00:00

Animal genetics, Vol. 29, No. 6. (December 1998), pp. 456-459.

Variation in the control region and the 12S rRNA gene of all surviving mitochondrial lineages of Przewalski's horse was investigated. Variation is low despite the present day population being descended from 13 individuals probably representing animals from three different regions of its range. Phylogenetic comparison of these sequences, with sequences for the domestic horse, does not resolve the ancestral status of either horse.

Distribution of the ERE-1 family in Perissodactyla.

M Sakagami — 2008-05-12T19:25:42-00:00

Mammalian genome : official journal of the International Mammalian Genome Society, Vol. 10, No. 9. (September 1999), pp. 930-933.

Refined genome-wide comparative map of the domestic horse, donkey and human based on cross-species chromosome painting: insight into the occasional fertility of mules.

F Yang — 2008-05-12T19:19:21-00:00

Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology, Vol. 12, No. 1. (2004), pp. 65-76.

We have made a complete set of painting probes for the domestic horse by degenerate oligonucleotide-primed PCR amplification of flow-sorted horse chromosomes. The horse probes, together with a full set of those available for human, were hybridized onto metaphase chromosomes of human, horse and mule. Based on the hybridization results, we have generated genome-wide comparative chromosome maps involving the domestic horse, donkey and human. These maps define the overall distribution and boundaries of evolutionarily conserved chromosomal segments in the three genomes. Our results shed further light on the karyotypic relationships among these species and, in particular, the chromosomal rearrangements that underlie hybrid sterility and the occasional fertility of mules.

A gene atlas of the mouse and human protein-encoding transcriptomes.

AI Su — 2006-03-03T12:15:01-00:00

Proc Natl Acad Sci U S A, Vol. 101, No. 16. (20 April 2004), pp. 6062-6067.

The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.

Mitochondrial 16S rRNA sequence diversity of hominoids.

R Noda — 2008-04-01T13:33:46-00:00

J Hered, Vol. 92, No. 6. (c 2001), pp. 490-496.

We determined nucleotide sequences of the 16S rRNA gene of mitochondrial DNA (mtDNA) (about 1.6 kb) for 35 chimpanzee, 13 bonobo, 10 gorilla, 16 orangutan, and 23 gibbon individuals. We compared those data with published sequences and estimated nucleotide diversity for each species. All the ape species showed higher diversity than human. We also constructed phylogenetic trees and networks. The two orangutan subspecies were clearly separated from each other, and Sumatran orangutans showed much higher nucleotide diversity than Bornean orangutans. Some gibbon species did not form monophyletic clusters, and variation within species was not much different from that among species in the subgenus Hylobates.

Genomic differentiation among natural populations of orang-utan (Pongo pygmaeus).

L Zhi — 2008-04-01T13:31:01-00:00

Curr Biol, Vol. 6, No. 10. (1 October 1996), pp. 1326-1336.

BACKGROUND: Orang-utans exist today in small isolated populations on the islands of Borneo (subspecies Pongo pygmaeus pygmaeus) and Sumatra (subspecies P. p. abelii). Although, on the basis of their morphological, behavioral and cytogenetical characteristics, the Bornean and Sumatran orang-utan populations are generally considered as two separate subspecies, there is no universal agreement as to whether their genetic differentiation is sufficient to consider and manage them as species, subspecies or population level taxonomic units. A more precise phylogenetic description would affect many conservation management decisions about captive and free-ranging orang-utans. RESULTS: We analyzed the amount and patterns of molecular genetic variation in orang-utan populations using cellular DNA from orang-utans from two locations in Sumatra and nine locations-representing four isolated populations-in Borneo. Genetic and phylogenetic analyses of mitochondrial DNA restriction fragment length polymorphisms, nuclear minisatellite (or variable number tandem repeat) loci and mitochondrial 16S ribosomal RNA sequences led to three major findings. First, the genetic distance and phylogenetic differentiation between Sumatran and Bornean orang-utans is large, greater than that between the common chimpanzee, Pan troglodytes, and the pygmy chimpanzee or bonobo, Pan paniscus. The genetic distance suggests that the two island subspecies diverged approximately 1.5-1.7 million years ago, well before the two islands separated and long enough for species-level differentiation. Second, there is considerable endemic genetic diversity within the Bornean and Sumatran orang-utan populations, suggesting that they have not experienced recent bottlenecks or founder effects. And third, there is little genetic differentiation among four geographically isolated populations of Bornean orang-utans, consistent with gene flow having occurred between them until recently. CONCLUSIONS: Our results are consistent with the view that the genetic differentiation between Sumatran and Bornean orang-utans has reached the level of distinct species. Furthermore, our findings indicate that there is not a genetic imperative for the separate management of geographically isolated Bornean populations.

mtDNA sequence diversity of orangutans from the islands of Borneo and Sumatra.

CC Muir — 2005-05-20T19:03:11-00:00

J Mol Evol, Vol. 51, No. 5. (November 2000), pp. 471-480.

A comparison of mitochondrial DNA sequences was undertaken for two genes among orangutans from Borneo and Sumatra. The distribution of haplotypes among 42 individuals for NADH dehydrogenease subunit 3 and 39 individuals for cytochrome B was used to infer population structure. The haplotypes among all Bornean orangutans form a cluster of closely related individuals for both genes, with two distinct haplotypes occupying different regions of the island. Sumatran haplotypes fall into three distinct, and highly diverged, groups. Strikingly, one of the Sumatran haplotypes shares sequence identity with the most widespread Bornean haplotype. This haplotype distribution is considered in the context of the highly complex geological history for the area around the Malay Archipelago. Alternating periods of geographic isolation and reunion, resulting from glacially induced land bridge formation, presented substantial opportunity for population dispersal between periodically isolated demes. We present a paleodispersal model that is consistent with genetic, geological, paleoecological, and fossil data. The disparity of sequences present in orangutan populations argues against a simple Sumatra-Borneo dichotomy. Our evidence, and that of others, suggests that the Sumatran population alone contains the remnants of at least three separate lineages.

Great ape DNA sequences reveal a reduced diversity and an expansion in humans.

H Kaessmann — 2006-05-26T23:20:08-00:00

Nat Genet, Vol. 27, No. 2. (February 2001), pp. 155-156.

The extent of DNA sequence variation of chimpanzees is several-fold greater than that of humans. It is unclear, however, if humans or chimpanzees are exceptional among primates in having low and high amounts of DNA sequence diversity, respectively. To address this, we have determined approximately 10,000 bp of noncoding DNA sequences at Xq13.3 (which has been extensively studied in both humans and chimpanzees) from 10 western lowland gorillas (Gorilla gorilla gorilla) and 1 mountain gorilla (Gorilla gorilla beringei; that is, from 2 of the 3 currently recognized gorilla subspecies), as well as 8 Bornean (Pongo pygmaeus pygmaeus) and 6 Sumatran (Pongo pygmaeus abelii) orang-utans, representing both currently recognized orang-utan subspecies. We show that humans differ from the great apes in having a low level of genetic variation and a signal of population expansion.

The genetical history of humans and the great apes.

H Kaessmann — 2008-04-01T13:23:09-00:00

J Intern Med, Vol. 251, No. 1. (January 2002), pp. 1-18.

When and where did modern humans evolve? How did our ancestors spread over the world? Traditionally, answers to questions such as these have been sought in historical, archaeological, and fossil records. However, increasingly genetic data provide information about the evolution of our species. In this review, we focus on the comparison of the variation in the human gene pool to that of our closest evolutionary relatives, the great apes, because this provides a relevant perspective on human genetical evolution. For instance, comparisons to the great apes show that humans are unique in having little genetic variation as well as little genetic structure in their gene pool. Furthermore, genetic data indicate that humans, but not the great apes, have experienced a period of dramatic growth in their early history.

Demographic Histories and Patterns of Linkage Disequilibrium in Chinese and Indian Rhesus Macaques

Ryan Hernandez — 2007-04-13T11:09:41-00:00

Science, Vol. 316, No. 5822. (13 April 2007), pp. 240-243.

To understand the demographic history of rhesus macaques (Macaca mulatta) and document the extent of linkage disequilibrium (LD) in the genome, we partially resequenced five Encyclopedia of DNA Elements regions in 9 Chinese and 38 captive-born Indian rhesus macaques. Population genetic analyses of the 1467 single-nucleotide polymorphisms discovered suggest that the two populations separated about 162,000 years ago, with the Chinese population tripling in size since then and the Indian population eventually shrinking by a factor of four. Using coalescent simulations, we confirmed that these inferred demographic events explain a much faster decay of LD in Chinese (r2 approx 0.15 at 10 kilobases) versus Indian (r2 approx 0.52 at 10 kilobases) macaque populations. 10.1126/science.1140462

The neighbor-joining method: a new method for reconstructing phylogenetic trees.

N Saitou — 2005-02-12T15:58:20-00:00

Mol Biol Evol, Vol. 4, No. 4. (July 1987), pp. 406-425.

A new method called the neighbor-joining method is proposed for reconstructing phylogenetic trees from evolutionary distance data. The principle of this method is to find pairs of operational taxonomic units (OTUs [= neighbors]) that minimize the total branch length at each stage of clustering of OTUs starting with a starlike tree. The branch lengths as well as the topology of a parsimonious tree can quickly be obtained by using this method. Using computer simulation, we studied the efficiency of this method in obtaining the correct unrooted tree in comparison with that of five other tree-making methods: the unweighted pair group method of analysis, Farris's method, Sattath and Tversky's method, Li's method, and Tateno et al.'s modified Farris method. The new, neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods.

Low nucleotide diversity in chimpanzees and bonobos.

N Yu — 2008-04-01T13:03:07-00:00

Genetics, Vol. 164, No. 4. (August 2003), pp. 1511-1518.

Comparison of the levels of nucleotide diversity in humans and apes may provide much insight into the mechanisms of maintenance of DNA polymorphism and the demographic history of these organisms. In the past, abundant mitochondrial DNA (mtDNA) polymorphism data indicated that nucleotide diversity (pi) is more than threefold higher in chimpanzees than in humans. Furthermore, it has recently been claimed, on the basis of limited data, that this is also true for nuclear DNA. In this study we sequenced 50 noncoding, nonrepetitive DNA segments randomly chosen from the nuclear genome in 9 bonobos and 17 chimpanzees. Surprisingly, the pi value for bonobos is only 0.078%, even somewhat lower than that (0.088%) for humans for the same 50 segments. The pi values are 0.092, 0.130, and 0.082% for East, Central, and West African chimpanzees, respectively, and 0.132% for all chimpanzees. These values are similar to or at most only 1.5 times higher than that for humans. The much larger difference in mtDNA diversity than in nuclear DNA diversity between humans and chimpanzees is puzzling. We speculate that it is due mainly to a reduction in effective population size (N(e)) in the human lineage after the human-chimpanzee divergence, because a reduction in N(e) has a stronger effect on mtDNA diversity than on nuclear DNA diversity. Sequence data from this article have been deposited with the GenBank Data libraries under accession nos. AY 275957-AY 277244.

Demographic History and Genetic Differentiation in Apes

Anne Fischer — 2007-12-18T14:55:51-00:00

Current Biology, Vol. 16, No. 11. (6 June 2006), pp. 1133-1138.

Summary Comparisons of genetic variation between humans and great apes are hampered by the fact that we still know little about the demographics and evolutionary history of the latter species 1, 2, 3 and 4. In addition, characterizing ape genetic variation is important because they are threatened with extinction, and knowledge about genetic differentiation among groups may guide conservation efforts [5]. We sequenced multiple intergenic autosomal regions totaling 22,400 base pairs (bp) in ten individuals each from western, central, and eastern chimpanzee groups and in nine bonobos, and 16,000 bp in ten Bornean and six Sumatran orangutans. These regions are analyzed together with homologous information from three human populations and gorillas. We find that whereas orangutans have the highest diversity, western chimpanzees have the lowest, and that the demographic histories of most groups differ drastically. Special attention should therefore be paid to sampling strategies and the statistics chosen when comparing levels of variation within and among groups. Finally, we find that the extent of genetic differentiation among "subspecies" of chimpanzees and orangutans is comparable to that seen among human populations, calling the validity of the "subspecies" concept in apes into question.

Evidence for a complex demographic history of chimpanzees.

A Fischer — 2008-04-01T12:58:19-00:00

Mol Biol Evol, Vol. 21, No. 5. (May 2004), pp. 799-808.

To characterize patterns of genomic variation in central chimpanzees (Pan troglodytes troglodytes) and gain insight into their evolution, we sequenced nine unlinked, intergenic regions, representing a total of 19,000 base pairs, in 14 individuals. When these DNA sequences are compared with homologous sequences previously collected in humans and in western chimpanzees (Pan troglodytes verus), nucleotide diversity is higher in central chimpanzees than in western chimpanzees or in humans. Consistent with a larger effective population size of central chimpanzees, levels of linkage disequilibrium are lower than in humans. Patterns of linkage disequilibrium further suggest that homologous gene conversion may be an important contributor to genetic exchange at short distances, in agreement with a previous study of the same DNA sequences in humans. In central chimpanzees, but not in western chimpanzees, the allele frequency spectrum is significantly skewed towards rare alleles, pointing to population size changes or fine-scale population structure. Strikingly, the extent of genetic differentiation between western and central chimpanzees is much stronger than what is seen between human populations. This suggests that careful attention should be paid to geographic sampling in studies of chimpanzee genetic variation.

A new paradigm for profiling testicular gene expression during normal and disturbed human spermatogenesis.

C Feig — 2008-01-14T22:43:48-00:00

Mol Hum Reprod, Vol. 13, No. 1. (January 2007), pp. 33-43.

The aim of this study was to identify gene expression patterns of the testis that correlate with the appearance of distinct stages of male germ cells. We avoided the pitfalls of mixed pathological phenotypes of the testis and circumvented the inapplicability of using the first spermatogenic wave as done previously on rodents. This was accomplished by using 28 samples showing defined and highly homogeneous pathologies selected from 578 testicular biopsies obtained from 289 men with azoospermia (two biopsies each). The molecular signature of the different developmental stages correlated with the morphological preclassification of the testicular biopsies, as shown by resampling-based hierarchical clustering using different measures of variability. By using analysis of variance (ANOVA) and extensive permutation analysis, we filtered 1181 genes that exhibit exceptional statistical significance in testicular expression and grouped subsets with transcriptional changes within the pre-meiotic (348 genes), post-meiotic (81 genes) and terminal differentiation (38 genes) phase. Several distinct molecular classes, metabolic pathways and transcription factor binding sites are involved, depending on the transcriptional profile of the gene clusters that were built using a novel clustering procedure based on not only similarity but also statistical significance.

The conserved transcriptome in human and rodent male gametogenesis

Frederic Chalmel — 2007-05-16T12:09:47-00:00

PNAS, Vol. 104, No. 20. (15 May 2007), pp. 8346-8351.

We report a cross-species expression profiling analysis of the human, mouse, and rat male meiotic transcriptional program, using enriched germ cell populations, whole gonads, and high-density oligonucleotide microarrays (GeneChips). Among 35% of the protein-coding genes present in rodent and human genomes that were found to be differentially expressed between germ cells and somatic controls, a key group of 357 conserved core loci was identified that displays highly similar meiotic and postmeiotic patterns of transcriptional induction across all three species. Genes known to be important for sexual reproduction are significantly enriched among differentially expressed core loci and a smaller group of conserved genes not detected in 17 nontesticular somatic tissues, correlating transcriptional activation and essential function in the male germ line. Some genes implicated in the etiology of cancer are found to be strongly transcribed in testis, suggesting that these genes may play unexpected roles in sexual reproduction. Expression profiling data further identified numerous conserved genes of biological and clinical interest previously unassociated with the mammalian male germ line. 10.1073/pnas.0701883104

Evolution of primate gene expression

Philipp Khaitovich — 2006-08-21T07:27:23-00:00

Nature Reviews Genetics, Vol. 7, No. 9., pp. 693-702.

Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees.

P Khaitovich — 2006-07-24T16:59:33-00:00

Science, Vol. 309, No. 5742. (16 September 2005), pp. 1850-1854.

The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.

The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells

Liqin Cao — 2007-02-27T01:55:19-00:00

Nature Genetics, Vol. 39, No. 3. (11 February 2007), pp. 386-390.

The UCSC Genome Browser Database: update 2006.

AS Hinrichs — 2006-02-21T15:18:40-00:00

Nucleic Acids Res, Vol. 34, No. Database issue. (1 January 2006)

The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at http://genome.ucsc.edu/.

AZFa deletions in Sertoli cell-only syndrome: a retrospective study.

O Blagosklonova — 2007-12-14T22:22:11-00:00

Mol Hum Reprod, Vol. 6, No. 9. (September 2000), pp. 795-799.

Lack of data on the genotype-phenotype relationship in cases of AZF microdeletions is due to the limited number of histological investigations in human male infertility cases. We investigated the possibility of retrospective detection of Yq11 microdeletions by using DNA extracted from diagnostic testicular biopsies. We used histological criteria to select two series of material: 22 biopsies with Sertoli cell-only syndrome and 14 biopsies with maturation arrest at the spermatocyte I stage. Two markers, DFFRY and DAZ, were tested by nested polymerase chain reaction (PCR) in the two series. In the Sertoli cell-only syndrome series, we found four deletions affecting the DFFRY gene (18.2%). In the second series, no deletions were detected. Two conclusions may be considered, although the number of specimens analysed is limited: (i) the frequency of deletions observed in Sertoli cell-only syndrome allows us to suggest that deletion in the AZFa region may be involved in this pathology; and (ii) retrospective studies may yield some additional elements in our search for eventual genotype-phenotype relationships.

An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y.

C Sun — 2007-12-14T22:20:55-00:00

Nat Genet, Vol. 23, No. 4. (December 1999), pp. 429-432.

In humans, deletion of any one of three Y-chromosomal regions- AZFa, AZFb or AZFc-disrupts spermatogenesis, causing infertility in otherwise healthy men. Although candidate genes have been identified in all three regions, no case of spermatogenic failure has been traced to a point mutation in a Y-linked gene, or to a deletion of a single Y-linked gene. We sequenced the AZFa region of the Y chromosome and identified two functional genes previously described: USP9Y (also known as DFFRY) and DBY (refs 7,8). Screening of the two genes in 576 infertile and 96 fertile men revealed several sequence variants, most of which appear to be heritable and of little functional consequence. We found one de novo mutation in USP9Y: a 4-bp deletion in a splice-donor site, causing an exon to be skipped and protein truncation. This mutation was present in a man with nonobstructive azoospermia (that is, no sperm was detected in semen), but absent in his fertile brother, suggesting that the USP9Y mutation caused spermatogenic failure. We also identified a single-gene deletion associated with spermatogenic failure, again involving USP9Y, by re-analysing a published study.

The human Y chromosome, in the light of evolution.

BT Lahn — 2007-12-14T22:19:37-00:00

Nat Rev Genet, Vol. 2, No. 3. (March 2001), pp. 207-216.

Most eukaryotic chromosomes, akin to messy toolboxes, store jumbles of genes with diverse biological uses. The linkage of a gene to a particular chromosome therefore rarely hints strongly at that gene's function. One striking exception to this pattern of gene distribution is the human Y chromosome. Far from being random and diverse, known human Y-chromosome genes show just a few distinct expression profiles. Their relative functional conformity reflects evolutionary factors inherent to sex-specific chromosomes.

Population and group structure of western lowland gorillas (

Sylvain Gatti — 2005-04-16T15:49:30-00:00

American Journal of Primatology, Vol. 63, No. 3. (13 July 2004), pp. 111-123.

During a 17-month study at the Lokoué clearing in Odzala National Park, Republic of Congo, we identified 377 western lowland gorillas. This population included 31 solitary males, 37 breeding groups, and eight nonbreeding groups. Its age- and sex-class structure was similar to those observed at two other clearings in the same forest block. However, the size of breeding groups varied with site (either clearing or forest sites). At Lokoué, breeding groups (mean size: 8.2 gorillas; range: 3-15) included a single silverback male and, on average, 3.2 adult females. Nonbreeding groups (mean size: 5.5; range: 2-15) were devoid of adult females. Five of the nonbreeding groups were composed predominantly of blackbacks, subadult males, and juveniles, and thus fit the definition of all-male groups previously observed in mountain gorillas. Our study confirms that 1) one-male breeding groups are the norm in western gorillas, and 2) all-male groups occur in this species. Despite frequent changes in members due to migrations of the males, the persistence of these all-male groups indicates that they may play an important role in the life of migrating males. Variations in population structure, and group composition and type among gorilla populations are discussed. However, a further understanding of the evolution of group-living in gorillas requires detailed ecological studies conducted in parallel with studies of the population structure and dynamics of these groups. Am. J. Primatol. 63:111-123, 2004. © 2004 Wiley-Liss, Inc.

The effect of life-history and mode of inheritance on neutral genetic variability.

B Charlesworth — 2007-12-14T22:14:18-00:00

Genet Res, Vol. 77, No. 2. (April 2001), pp. 153-166.

Formulae for the effective population sizes of autosomal, X-linked, Y-linked and maternally transmitted loci in age-structured populations are developed. The approximations used here predict both asymptotic rates of increase in probabilities of identity, and equilibrium levels of neutral nucleotide site diversity under the infinite-sites model. The applications of the results to the interpretation of data on DNA sequence variation in Drosophila, plant, and human populations are discussed. It is concluded that sex differences in demographic parameters such as adult mortality rates generally have small effects on the relative effective population sizes of loci with different modes of inheritance, whereas differences between the sexes in variance in reproductive success can have major effects, either increasing or reducing the effective population size for X-linked loci relative to autosomal or Y-linked loci. These effects need to be accounted for when trying to understand data on patterns of sequence variation for genes with different transmission modes.

Simple Methods for Testing the Molecular Evolutionary Clock Hypothesis

F Tajima — 2006-08-03T23:35:19-00:00

Genetics, Vol. 135, No. 2. (1 October 1993), pp. 599-607.

Estimation of divergence times for major lineages of primate species.

GV Glazko — 2007-12-14T19:30:53-00:00

Mol Biol Evol, Vol. 20, No. 3. (March 2003), pp. 424-434.

Although the phylogenetic relationships of major lineages of primate species are relatively well established, the times of divergence of these lineages as estimated by molecular data are still controversial. This controversy has been generated in part because different authors have used different types of molecular data, different statistical methods, and different calibration points. We have therefore examined the effects of these factors on the estimates of divergence times and reached the following conclusions: (1) It is advisable to concatenate many gene sequences and use a multigene gamma distance for estimating divergence times rather than using the individual gene approach. (2) When sequence data from many nuclear genes are available, protein sequences appear to give more robust estimates than DNA sequences. (3) Nuclear proteins are generally more suitable than mitochondrial proteins for time estimation. (4) It is important first to construct a phylogenetic tree for a group of species using some outgroups and then estimate the branch lengths. (5) It appears to be better to use a few reliable calibration points rather than many unreliable ones. Considering all these factors and using two calibration points, we estimated that the human lineage diverged from the chimpanzee, gorilla, orangutan, Old World monkey, and New World monkey lineages approximately 6 MYA (with a range of 5-7), 7 MYA (range, 6-8), 13 MYA (range, 12-15), 23 MYA (range, 21-25), and 33 MYA (range 32-36).

Extensive nuclear DNA sequence diversity among chimpanzees.

H Kaessmann — 2007-12-14T19:28:23-00:00

Science, Vol. 286, No. 5442. (5 November 1999), pp. 1159-1162.

Although data on nucleotide sequence variation in the human nuclear genome have begun to accumulate, little is known about genomic diversity in chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). A 10,154-base pair sequence on the chimpanzee X chromosome is reported, representing all major subspecies and bonobos. Comparison to humans shows the diversity of the chimpanzee sequences to be almost four times as high and the age of the most recent common ancestor three times as great as the corresponding values of humans. Phylogenetic analyses show the sequences from the different chimpanzee subspecies to be intermixed and the distance between some chimpanzee sequences to be greater than the distance between them and the bonobo sequences.

Nucleotide diversity in gorillas.

N Yu — 2007-12-14T19:25:00-00:00

Genetics, Vol. 166, No. 3. (March 2004), pp. 1375-1383.

Comparison of the levels of nucleotide diversity in humans and apes may provide valuable information for inferring the demographic history of these species, the effect of social structure on genetic diversity, patterns of past migration, and signatures of past selection events. Previous DNA sequence data from both the mitochondrial and the nuclear genomes suggested a much higher level of nucleotide diversity in the African apes than in humans. Noting that the nuclear DNA data from the apes were very limited, we previously conducted a DNA polymorphism study in humans and another in chimpanzees and bonobos, using 50 DNA segments randomly chosen from the noncoding, nonrepetitive parts of the human genome. The data revealed that the nucleotide diversity (pi) in bonobos (0.077%) is actually lower than that in humans (0.087%) and that pi in chimpanzees (0.134%) is only 50% higher than that in humans. In the present study we sequenced the same 50 segments in 15 western lowland gorillas and estimated pi to be 0.158%. This is the highest value among the African apes but is only about two times higher than that in humans. Interestingly, available mtDNA sequence data also suggest a twofold higher nucleotide diversity in gorillas than in humans, but suggest a threefold higher nucleotide diversity in chimpanzees than in humans. The higher mtDNA diversity in chimpanzees might be due to the unique pattern in the evolution of chimpanzee mtDNA. From the nuclear DNA pi values, we estimated that the long-term effective population sizes of humans, bonobos, chimpanzees, and gorillas are, respectively, 10,400, 12,300, 21,300, and 25,200.

The effects of Hill-Robertson interference between weakly selected mutations on patterns of molecular evolution and variation.

GA McVean — 2007-12-14T19:23:28-00:00

Genetics, Vol. 155, No. 2. (June 2000), pp. 929-944.

Associations between selected alleles and the genetic backgrounds on which they are found can reduce the efficacy of selection. We consider the extent to which such interference, known as the Hill-Robertson effect, acting between weakly selected alleles, can restrict molecular adaptation and affect patterns of polymorphism and divergence. In particular, we focus on synonymous-site mutations, considering the fate of novel variants in a two-locus model and the equilibrium effects of interference with multiple loci and reversible mutation. We find that weak selection Hill-Robertson (wsHR) interference can considerably reduce adaptation, e.g., codon bias, and, to a lesser extent, levels of polymorphism, particularly in regions of low recombination. Interference causes the frequency distribution of segregating sites to resemble that expected from more weakly selected mutations and also generates specific patterns of linkage disequilibrium. While the selection coefficients involved are small, the fitness consequences of wsHR interference across the genome can be considerable. We suggest that wsHR interference is an important force in the evolution of nonrecombining genomes and may explain the unexpected constancy of codon bias across species of very different census population sizes, as well as several unusual features of codon usage in Drosophila.

Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution.

Z Yang — 2006-04-10T17:17:51-00:00

Mol Biol Evol, Vol. 15, No. 5. (May 1998), pp. 568-573.

An excess of nonsynonymous substitutions over synonymous ones is an important indicator of positive selection at the molecular level. A lineage that underwent Darwinian selection may have a nonsynonymous/synonymous rate ratio (dN/dS) that is different from those of other lineages or greater than one. In this paper, several codon-based likelihood models that allow for variable dN/dS ratios among lineages were developed. They were then used to construct likelihood ratio tests to examine whether the dN/dS ratio is variable among evolutionary lineages, whether the ratio for a few lineages of interest is different from the background ratio for other lineages in the phylogeny, and whether the dN/dS ratio for the lineages of interest is greater than one. The tests were applied to the lysozyme genes of 24 primate species. The dN/dS ratios were found to differ significantly among lineages, indicating that the evolution of primate lysozymes is episodic, which is incompatible with the neutral theory. Maximum-likelihood estimates of parameters suggested that about nine nonsynonymous and zero synonymous nucleotide substitutions occurred in the lineage leading to hominoids, and the dN/dS ratio for that lineage is significantly greater than one. The corresponding estimates for the lineage ancestral to colobine monkeys were nine and one, and the dN/dS ratio for the lineage is not significantly greater than one, although it is significantly higher than the background ratio. The likelihood analysis thus confirmed most, but not all, conclusions Messier and Stewart reached using reconstructed ancestral sequences to estimate synonymous and nonsynonymous rates for different lineages.

PAML: a program package for phylogenetic analysis by maximum likelihood.

Z Yang — 2005-11-25T12:56:07-00:00

Comput Appl Biosci, Vol. 13, No. 5. (October 1997), pp. 555-556.

MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) Software Version 4.0

Koichiro Tamura — 2007-08-02T18:57:54-00:00

Mol Biol Evol, Vol. 24, No. 8. (1 August 2007), pp. 1596-1599.

We announce the release of the fourth version of MEGA software, which expands on the existing facilities for editing DNA sequence data from autosequencers, mining Web-databases, performing automatic and manual sequence alignment, analyzing sequence alignments to estimate evolutionary distances, inferring phylogenetic trees, and testing evolutionary hypotheses. Version 4 includes a unique facility to generate captions, written in figure legend format, in order to provide natural language descriptions of the models and methods used in the analyses. This facility aims to promote a better understanding of the underlying assumptions used in analyses, and of the results generated. Another new feature is the Maximum Composite Likelihood (MCL) method for estimating evolutionary distances between all pairs of sequences simultaneously, with and without incorporating rate variation among sites and substitution pattern heterogeneities among lineages. This MCL method also can be used to estimate transition/transversion bias and nucleotide substitution pattern without knowledge of the phylogenetic tree. This new version is a native 32-bit Windows application with multi-threading and multi-user supports, and it is also available to run in a Linux desktop environment (via the Wine compatibility layer) and on Intel-based Macintosh computers under the Parallels program. The current version of MEGA is available free of charge at http://www.megasoftware.net. 10.1093/molbev/msm092

Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees.

K Tamura — 2007-12-06T22:03:56-00:00

Mol Biol Evol, Vol. 10, No. 3. (May 1993), pp. 512-526.

Examining the pattern of nucleotide substitution for the control region of mitochondrial DNA (mtDNA) in humans and chimpanzees, we developed a new mathematical method for estimating the number of transitional and transversional substitutions per site, as well as the total number of nucleotide substitutions. In this method, excess transitions, unequal nucleotide frequencies, and variation of substitution rate among different sites are all taken into account. Application of this method to human and chimpanzee data suggested that the transition/transversion ratio for the entire control region was approximately 15 and nearly the same for the two species. The 95% confidence interval of the age of the common ancestral mtDNA was estimated to be 80,000-480,000 years in humans and 0.57-2.72 Myr in common chimpanzees.

High levels of Y-chromosome nucleotide diversity in the genus Pan.

AC Stone — 2007-12-06T22:01:09-00:00

Proc Natl Acad Sci U S A, Vol. 99, No. 1. (8 January 2002), pp. 43-48.

Although some mitochondrial, X chromosome, and autosomal sequence diversity data are available for our closest relatives, Pan troglodytes and Pan paniscus, data from the nonrecombining portion of the Y chromosome (NRY) are more limited. We examined approximately 3 kb of NRY DNA from 101 chimpanzees, seven bonobos, and 42 humans to investigate: (i) relative levels of intraspecific diversity; (ii) the degree of paternal lineage sorting among species and subspecies of the genus Pan; and (iii) the date of the chimpanzee/bonobo divergence. We identified 10 informative sequence-tagged sites associated with 23 polymorphisms on the NRY from the genus Pan. Nucleotide diversity was significantly higher on the NRY of chimpanzees and bonobos than on the human NRY. Similar to mtDNA, but unlike X-linked and autosomal loci, lineages defined by mutations on the NRY were not shared among subspecies of P. troglodytes. Comparisons with mtDNA ND2 sequences from some of the same individuals revealed a larger female versus male effective population size for chimpanzees. The NRY-based divergence time between chimpanzees and bonobos was estimated at approximately 1.8 million years ago. In contrast to human populations who appear to have had a low effective size and a recent origin with subsequent population growth, some taxa within the genus Pan may be characterized by large populations of relatively constant size, more ancient origins, and high levels of subdivision.

The WD repeat: a common architecture for diverse functions.

TF Smith — 2007-12-06T21:59:10-00:00

Trends Biochem Sci, Vol. 24, No. 5. (May 1999), pp. 181-185.

Our knowledge of the large family of proteins that contain the WD repeat continues to accumulate. The WD-repeat proteins are found in all eukaryotes and are implicated in a wide variety of crucial functions. The solution of the three-dimensional structure of one WD-repeat protein and the assumption that the structure will be common to all members of this family has allowed subfamilies of WD-repeat proteins to be defined on the basis of probable surface similarity. Proteins that have very similar surfaces are likely to have common binding partners and similar functions.

Divergence of the genes on human chromosome 21 between human and other hominoids and variation of substitution rates among transcription units.

J Shi — 2006-08-10T10:52:28-00:00

Proc Natl Acad Sci U S A, Vol. 100, No. 14. (8 July 2003), pp. 8331-8336.

The study of genomic divergence between humans and primates may provide insight into the origins of human beings and the genetic basis of unique human traits and diseases. Chromosome 21 is the smallest chromosome in the human genome, and some of its regions have been implicated in mental retardation and other diseases. In this study, we sequenced the coding and regulatory regions of 127 known genes on human chromosome 21 in DNA samples from human and chimpanzees and a part of the corresponding genes from orangutan, gorilla, and macaque. Overall, 3,003 nucleotide differences between human and chimpanzee were identified over approximately 400 kb. The differences in coding, promoter, and exon-intron junction regions were 0.51 +/- 0.02%, 0.88 +/- 0.03%, and 0.85 +/- 0.02%, respectively, much lower than the previously reported 1.23% in genomic regions, which suggests the presence of purifying selection. Significant variation in substitution rate among genes was observed by comparing the divergence between human and chimpanzee. Furthermore, by implementing a bioinformatics-based approach, we showed that the identification of genetic variants specific to the human lineage might lead to an understanding of the mechanisms that are attributable to the phenotypes that unique to humans, by changing the structure and/or dosage of the proteins expressed. A phylogenetic analysis unambiguously confirms the conclusion that chimpanzees were our closest relatives to the exclusion of other primates and the relative divergence of the Homo-Pan and that of (Homo-Pan)-Gorilla are 4.93 million years and 7.26 million years, respectively.

Primer3 on the WWW for general users and for biologist programmers.

S Rozen — 2006-03-29T15:20:49-00:00

Methods Mol Biol, Vol. 132 (2000), pp. 365-386.

Genetic hitchhiking and the evolution of reduced genetic activity of the Y sex chromosome.

WR Rice — 2007-12-06T21:47:28-00:00

Genetics, Vol. 116, No. 1. (May 1987), pp. 161-167.

A new model for the evolution of reduced genetic activity of the Y sex chromosome is described. The model is based on the process of genetic hitchhiking. It is shown that the Y chromosome can gradually lose its genetic activity due to the fixation of deleterious mutations that are linked with other beneficial genes. Fixation of deleterious Y-linked mutations generates locus-specific selection for dosage tolerance and/or compensation. The hitchhiking effect is most pronounced when operating in combination with an alternative model, Muller's ratchet. It is shown, however, that the genetic hitchhiking mechanism can operate under conditions where Muller's ratchet is ineffective.

Regulation of actin filament dynamics by actin depolymerizing factor/cofilin and actin-interacting protein 1: new blades for twisted filaments.

S Ono — 2007-12-06T21:43:07-00:00

Biochemistry, Vol. 42, No. 46. (25 November 2003), pp. 13363-13370.

Actin depolymerizing factor (ADF)/cofilin enhances turnover of actin filaments by severing and depolymerizing filaments. A number of proteins functionally interact with ADF/cofilin to modulate the dynamics of actin filaments. Actin-interacting protein 1 (AIP1) has emerged as a conserved WD-repeat protein that specifically enhances ADF/cofilin-induced actin dynamics. Interaction of AIP1 with actin was originally characterized by a yeast two-hybrid system. However, biochemical studies revealed its unique activity on ADF/cofilin-bound actin filaments. AIP1 alone has negligible effects on actin filament dynamics, whereas in the presence of ADF/cofilin, AIP1 enhances filament fragmentation by capping ends of severed filaments. Studies in model organisms demonstrated that AIP1 genetically interacts with ADF/cofilin and participates in several actin-dependent cellular events. The crystal structure of AIP1 revealed its unique structure with two seven-bladed beta-propeller domains. Thus, AIP1 is a new class of actin regulatory proteins that selectively enhances ADF/cofilin-dependent actin filament dynamics.

THE RELATION OF RECOMBINATION TO MUTATIONAL ADVANCE.

HJ MULLER — 2007-12-06T21:39:46-00:00

Mutat Res, Vol. 106 (May 1964), pp. 2-9.

The hitch-hiking effect of a favourable gene.

J Maynard-Smith — 2007-09-06T09:54:47-00:00

Genet Res, Vol. 23, No. 1. (February 1974), pp. 23-35.

Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.

M Nei — 2006-09-08T08:55:13-00:00

Mol Biol Evol, Vol. 3, No. 5. (September 1986), pp. 418-426.

Two simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions are presented. Although they give no weights to different types of codon substitutions, these methods give essentially the same results as those obtained by Miyata and Yasunaga's and by Li et al.'s methods. Computer simulation indicates that estimates of synonymous substitutions obtained by the two methods are quite accurate unless the number of nucleotide substitutions per site is very large. It is shown that all available methods tend to give an underestimate of the number of nonsynonymous substitutions when the number is large.

Strong male-driven evolution of DNA sequences in humans and apes

Kateryna Makova — 2007-10-17T17:20:21-00:00

Nature, Vol. 416, No. 6881. (11 April 2002), pp. 624-626.

Male-driven evolution.

WH Li — 2007-10-17T17:21:47-00:00

Curr Opin Genet Dev, Vol. 12, No. 6. (December 2002), pp. 650-656.

The strength of male-driven evolution - that is, the magnitude of the sex ratio of mutation rate - has been a controversial issue, particularly in primates. While earlier studies estimated the male-to-female ratio (alpha) of mutation rate to be about 4-6 in higher primates, two recent studies claimed that alpha is only about 2 in humans. However, a more recent comparison of mutation rates between a noncoding fragment on Y and a homologous region on chromosome 3 gave an estimate of alpha = 5.3, reinstating strong male-driven evolution in hominoids. Several studies investigated variation in mutation rates among genomic regions that may not be related to sex differences and found strong evidence for such variation. The causes for regional variation in mutation rate are not clear but GC content and recombination are two possible causes. Thus, while the strong male-driven evolution in higher primates suggests that errors during DNA replication in the germ cells are the major source of mutation, the contribution of some replication-independent factors such as recombination may also be important.

Four evolutionary strata on the human X chromosome.

BT Lahn — 2007-12-06T21:30:15-00:00

Science, Vol. 286, No. 5441. (29 October 1999), pp. 964-967.

Human sex chromosomes evolved from autosomes. Nineteen ancestral autosomal genes persist as differentiated homologs on the X and Y chromosomes. The ages of individual X-Y gene pairs (measured by nucleotide divergence) and the locations of their X members on the X chromosome were found to be highly correlated. Age decreased in stepwise fashion from the distal long arm to the distal short arm in at least four "evolutionary strata." Human sex chromosome evolution was probably punctuated by at least four events, each suppressing X-Y recombination in one stratum, without disturbing gene order on the X chromosome. The first event, which marked the beginnings of X-Y differentiation, occurred about 240 to 320 million years ago, shortly after divergence of the mammalian and avian lineages.

Comparative analysis of chimpanzee and human Y chromosomes unveils complex evolutionary pathway.

Yoko Kuroki — 2006-01-04T08:51:10-00:00

Nat Genet (1 January 2006)

The mammalian Y chromosome has unique characteristics compared with the autosomes or X chromosomes. Here we report the finished sequence of the chimpanzee Y chromosome (PTRY), including 271 kb of the Y-specific pseudoautosomal region 1 and 12.7 Mb of the male-specific region of the Y chromosome. Greater sequence divergence between the human Y chromosome (HSAY) and PTRY (1.78%) than between their respective whole genomes (1.23%) confirmed the accelerated evolutionary rate of the Y chromosome. Each of the 19 PTRY protein-coding genes analyzed had at least one nonsynonymous substitution, and 11 genes had higher nonsynonymous substitution rates than synonymous ones, suggesting relaxation of selective constraint, positive selection or both. We also identified lineage-specific changes, including deletion of a 200-kb fragment from the pericentromeric region of HSAY, expansion of young Alu families in HSAY and accumulation of young L1 elements and long terminal repeat retrotransposons in PTRY. Reconstruction of the common ancestral Y chromosome reflects the dynamic changes in our genomes in the 5-6 million years since speciation.

Sperm Competition and mating behavior

T Hasegawa — 2007-12-06T21:26:51-00:00

(1990), pp. 115-132.