A maximum likelihood method for inferring evolutionary trees from DNA sequence data was developed by Felsenstein (1981). In evaluating the extent to which the maximum likelihood tree is a significantly better representation of the true tree, it is important to estimate the variance of the difference between log likelihood of different tree topologies. Bootstrap resampling can be used for this purpose (Hasegawa et al. 1988; Hasegawa and Kishino 1989), but it imposes a great computation burden. To overcome this difficulty, we developed a new method for estimating the variance by expressing it explicitly. The method was applied to DNA sequence data from primates in order to evaluate the maximum likelihood branching order among Hominoidea. It was shown that, although the orangutan is convincingly placed as an outgroup of a human and African apes clade, the branching order among human, chimpanzee, and gorilla cannot be determined confidently from the DNA sequence data presently available when the evolutionary rate constancy is not assumed.

Evaluation of the maximum likelihood estimate of the evolutionary tree topologies from DNA sequence data, and the branching order in hominoidea

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

/pdf/genome-sequence-comparative-analysis-and-haplotype-structure-2w9dmwssyq.pdf

Genome sequence, comparative analysis and haplotype structure of the domestic dog

The coding region of the mat K gene and two intergenic spacers, psb A-trn H and trn L(UAA)-trn F(GAA), of cpDNA were sequenced to study phylogenetic relationships of 32 Paeonia species. In the psb A-trn H intergenic spacer, short sequences bordered by long inverted repeats have undergone inversions that are often homoplasious mutations. Insertions/deletions found in the two intergenic spacers, mostly resulting from slipped-strand mispairing, provided relatively reliable phylogenetic information. The mat K coding region, evolving more rapidly than the trnL-trn F spacer and more slowly than the psb A-trn H spacer, produced the best resolved phylogenetic tree. The mat K phylogeny was compared with the phylogeny obtained from sequences of internal transcribed spacers (ITS) of nuclear ribosomal DNA. A refined hypothesis of species phylogeny of section Paeonia was proposed by considering the discordance between the nuclear and cpDNA phylogenies to be results of hybrid speciation followed by inheritance of cpDNA of one parent and fixation of ITS sequences of another parent. The Eurasian and western North American disjunct distribution of the genus may have resulted from interrruption of the continuous distribution of ancestral populations of extant peony species across the Bering land bridge during the Miocene. Pleistocene glaciation may have played an important role in triggering extensive reticulate evolution within section Paeonia and shifting distributional ranges of both parental and hybrid species.

Chloroplast DNA phylogeny, reticulate evolution, and biogeography of Paeonia (Paeoniaceae).

To investigate the time course of speciation, we gathered literature data on 119 pairs of closely related Drosophila species with known genetic distances, mating discrimination, strength of hybrid sterility and inviability, and geographic ranges. Because genetic distance is correlated with divergence time, these data provide a cross-section of taxa at different stages of speciation. Mating discrimination and the sterility or inviability of hybrids increase gradually with time. Hybrid sterility and inviability evolve at similar rates. Among allopatric species, mating discrim- ination and postzygotic isolation evolve at comparable rates, but among sympatric species strong mating discrimination appears well before severe sterility or inviability. This suggests that pre- zygotic reproductive isolation may be reinforced when allopatric taxa become sympatric. Analysis of the evolution of postzygotic isolation shows that recently diverged taxa usually produce sterile or inviable male but not female hybrids. Moreover, there is a large temporal gap between the evolution of male-limited and female hybrid sterility or inviability. This gap, which is predicted by recent theories about the genetics of speciation, explains the overwhelming pre- ponderance of hybridizations yielding male-limited hybrid sterility or inviability (Haldane's rule).

http://max2.ese.u-psud.fr/epc/conservation/PDFs/HIPE/Coyne1989.pdf

Patterns of speciation in drosophila.

The distribution of fitness effects (DFE) of new mutations is a fundamental entity in genetics that has implications ranging from the genetic basis of complex disease to the stability of the molecular clock. It has been studied by two different approaches: mutation accumulation and mutagenesis experiments, and the analysis of DNA sequence data. The proportion of mutations that are advantageous, effectively neutral and deleterious varies between species, and the DFE differs between coding and non-coding DNA. Despite these differences between species and genomic regions, some general principles have emerged: advantageous mutations are rare, and those that are strongly selected are exponentially distributed; and the DFE of deleterious mutations is complex and multi-modal.

/pdf/the-distribution-of-fitness-effects-of-new-mutations-1u1anx478f.pdf

The distribution of fitness effects of new mutations

Apolipoprotein (apo) B-100, the major protein component in low density lipoprotein (LDL), is the ligand that binds to the LDL receptor1. It is important in the metabolism of LDL and elevated plasma levels of LDL-apo B are strongly associated with increased risk of coronary artery disease. Although apo B-100 is of great clinical and biological importance its primary structure has defied chemical elucidation, mainly because of its enormous size, insolubility, and tendency to aggregate2. Less than 5% of the apo B-100 sequence has been reported, despite the efforts of many laboratories over the past twenty years. Here we report the complete amino acid sequence of human apo B-100 as deducted by sequence analysis of complementary DNA clones; 2,366 of the 4,536 residues were also confirmed by direct sequencing of apo B-100 tryptic peptides. The distribution of trypsin-accessible and -inaccessible peptides of the protein on LDL is non-random and they can be grouped into 5 hypothetical domains. Of 20 potential N-glycosylation sites identified in the sequence, 13 were foundry direct peptide sequencing to be glycosylated, and 4 unglycosylated. Examination of the primary structure of apo B-100 reveals that it contains a large number of long (>70 residues) internal repeats and an even larger number of shorter ones, suggesting that the apo B-100 sequence was derived largely from internal duplications. Finally, using synthetic peptides of a specific region of apo B-100, we have identified a potential LDL receptor-binding domain (residues 3,345–3,381) which can bind to the LDL receptor and suppress 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase activities in cultured human fibroblasts.

Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100.

A statistical analysis of extensive DNA sequence data from primates, rodents, and artiodacytls clearly indicates that no global molecular clock exists in mammals. Rates of nucleotide subsitution in rodents are estimated to be four to eight times higher than those in higher primates and two to four times higher than those in artiodactyls. There is strong evidence for lower substitution rates in apes and humans than in monkeys, supporting the hominoid slowdown hypothesis. There is also evidence for lower rates in humans than in apes, suggesting a further rate slowdown in the human lineage after the separation of humans from apes. By contrast, substitution rates are nearly equal in mouse and rat. These results suggest that differences in generation time or, more precisely, in the number of germline DNA replications per year are the primary cause of rate differences in mammals. Further, these differences are more in line with the neutral mutation hypothesis than if the rates are the same for short-and long-living mammals.

An evaluation of the molecular clock hypothesis using mammalian DNA sequences.

The molecular clock hypothesis1 postulates that the rate of molecular evolution is approximately constant over time. Although this hypothesis has been highly controversial in the past, it is now widely accepted2–5. The assumption of rate constancy has often been taken as a basis for reconstructing the phylogenetic relationships among organisms or genes and for dating evolutionary events2–5. Further, it has been taken as strong support for the neutral mutation hypothesis5, which postulates that the majority of molecular changes in evolution are due to neutral or nearly neutral mutations6. For these reasons, the validity of the rate constancy assumption is a vital issue in molecular evolution. Recent studies7–12 using DNA sequence data have raised serious doubts about the hypothesis. These studies provided support for the suggestion made from immunological distance and protein sequence data13,14 that a rate slowdown has occurred in hominoid evolution, and showed, in agreement with DNA hybridization studies15,16, that rates of nucleotide substitution are significantly higher in rodents than in man. Here, rates of nucleotide substitution in rodents are estimated to be 4–10 times higher than those in higher primates and 2–4 times higher than those in artiodactyls. Further, this study provides strong evidence for the hominoid slowdown hypothesis13,14 and suggests a further rate-slowdown in hominoid evolution. Our results suggest that the variation in rate among mammals is primarily due to differences in generation time8,16 rather than changes in DNA repair mechanisms9. We also propose a method for estimating the divergence times between species when the rate constancy assumption is violated.

The molecular clock runs more slowly in man than in apes and monkeys.

The apolipoprotein multigene family: biosynthesis, structure, structure-function relationships, and evolution.

The acquired immune deficiency syndrome (AIDS), caused by a retrovirus called human immunodeficiency virus (HIV), has become a pandemic. A knowledge of the rate of nucleotide substitution in HIV and of the history and pattern of spread of the virus is important for understanding the epidemiology and pathogenesis of AIDS and for developing therapies and vaccine strategies. A new model has been developed and used to estimate the substitution rates in various regions in the HIV genome. The rate of nonsynonymous (amino acid-changing) substitution is lowest in the regions coding for the capsid proteins and the reverse transcriptase, being - 1.7 X 1 OW3 nucleotide substitutions/site/year. The nonsynonymous rate is extremely high ( 14 X 1 Om3) in the hypervariable regions of the envelope gene, suggesting extremely rapid change in viral antigenicity. The nonsynonymous rates in the other coding regions are between 3 X 10m3 and 7 X 10e3. The average synonymous rate for the HIV genome is 10 X 10m3. These rates are lo6 times greater than the rates in DNA genomes and at least as high as the rates in other RNA viruses. Evidence is provided for a case of recombination between different HIV strains. Our analysis suggests that the AIDS virus had existed in central Africa before 1960 and spread to North America before the mid 1970s. The evolutionary relationships among HIV isolates are inferred from nucleotide sequence data, and the result is consistent with the view that AIDS spread from Haiti to the United States.

Masako Tanimura

Papers

Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100.

An evaluation of the molecular clock hypothesis using mammalian DNA sequences.

The molecular clock runs more slowly in man than in apes and monkeys.

The apolipoprotein multigene family: biosynthesis, structure, structure-function relationships, and evolution.

Rates and dates of divergence between AIDS virus nucleotide sequences.