Rapid evolution of male reproductive genes in the descent of man

A diverse body of morphological and genetic evidence has suggested that traits pertaining to male reproduction may have evolved much more rapidly than other types of character. Recently, DNA sequence comparisons have also shown a very high level of divergence in male reproductive proteins between closely related Drosophila species, among marine invertebrates and between mouse and rat. Here we show that rapid evolution of male reproductive genes is observable in primates and is quite notable in the lineages to human and chimpanzee. Nevertheless, rapid evolution by itself is not necessarily an indication of positive darwinian selection; relaxation of negative selection is often equally compatible with the DNA sequence data. By taking three statistical approaches, we show that positive darwinian selection is often the driving force behind this rapid evolution. These results open up opportunities to test the hypothesis that sexual selection plays some role in the molecular evolution of higher primates.     

Testing the neutral theory of molecular evolution with genomic data from Drosophila

Although positive selection has been detected in many genes, its overall contribution to protein evolution is debatable. If the bulk of molecular evolution is neutral, then the ratio of amino-acid (A) to synonymous (S) polymorphism should, on average, equal that of divergence. A comparison of the A/S ratio of polymorphism in Drosophila melanogaster with that of divergence from Drosophila simulans shows that the A/S ratio of divergence is twice as high---a difference that is often attributed to positive selection. But an increase in selective constraint owing to an increase in effective population size could also explain this observation, and, if so, all genes should be affected similarly. Here we show that the difference between polymorphism and divergence is limited to only a fraction of the genes, which are also evolving more rapidly, and this implies that positive selection is responsible. A higher A/S ratio of divergence than of polymorphism is also observed in other species, which suggests a rate of adaptive evolution that is far higher than permitted by the neutral theory of molecular evolution.     

Evolution of genes and genomes on the Drosophila phylogeny

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.     

Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila

Speciation--the splitting of one species into two--occurs by the evolution of any of several forms of reproductive isolation between taxa, including the intrinsic sterility and inviability of hybrids. Abundant evidence shows that these hybrid fitness problems are caused by incompatible interactions between loci: new alleles that become established in one species are sometimes functionally incompatible with alleles at interacting loci from another species. However, almost nothing is known about the genes involved in such hybrid incompatibilities or the evolutionary forces that drive their divergence. Here we identify a gene that causes epistatic inviability in hybrids between two fruitfly species, Drosophila melanogaster and D. simulans. Our population genetic analysis reveals that this gene--which encodes a nuclear pore protein--evolved by positive natural selection in both species' lineages. These results show that a lethal hybrid incompatibility has evolved as a by-product of adaptive protein evolution.     

Adaptive protein evolution at the Adh locus in Drosophila

Proteins often differ in amino-acid sequence across species. This difference has evolved by the accumulation of neutral mutations by random drift, the fixation of adaptive mutations by selection, or a mixture of the two. Here we propose a simple statistical test of the neutral protein evolution hypothesis based on a comparison of the number of amino-acid replacement substitutions to synonymous substitutions in the coding region of a locus. If the observed substitutions are neutral, the ratio of replacement to synonymous fixed differences between species should be the same as the ratio of replacement to synonymous polymorphisms within species. DNA sequence data on the Adh locus (encoding alcohol dehydrogenase, EC 1.1.1.1) in three species in the Drosophila melanogaster species subgroup do not fit this expectation; instead, there are more fixed replacement differences between species than expected. We suggest that these excess replacement substitutions result from adaptive fixation of selectively advantageous mutations.     

Gene expression divergence recapitulates the developmental hourglass model

The observation that animal morphology tends to be conserved during the embryonic phylotypic period (a period of maximal similarity between the species within each animal phylum) led to the proposition that embryogenesis diverges more extensively early and late than in the middle, known as the hourglass model. This pattern of conservation is thought to reflect a major constraint on the evolution of animal body plans. Despite a wealth of morphological data confirming that there is often remarkable divergence in the early and late embryos of species from the same phylum, it is not yet known to what extent gene expression evolution, which has a central role in the elaboration of different animal forms, underpins the morphological hourglass pattern. Here we address this question using species-specific microarrays designed from six sequenced Drosophila species separated by up to 40 million years. We quantify divergence at different times during embryogenesis, and show that expression is maximally conserved during the arthropod phylotypic period. By fitting different evolutionary models to each gene, we show that at each time point more than 80% of genes fit best to models incorporating stabilizing selection, and that for genes whose evolutionarily optimal expression level is the same across all species, selective constraint is maximized during the phylotypic period. The genes that conform most to the hourglass pattern are involved in key developmental processes. These results indicate that natural selection acts to conserve patterns of gene expression during mid-embryogenesis, and provide a genome-wide insight into the molecular basis of the hourglass pattern of developmental evolution.     

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.     

Sympatric speciation by sexual selection

There is increasing evidence for the process of sympatric speciation, in which reproductive isolation of species occurs without physical isolation. Theoretical models have focused on disruptive natural selection as the crucial pressure for splitting a species. Here we report the theoretical finding that sympatric speciation may be caused by sexual selection even without disruptive natural selection. Specifically, we show that variation in a male secondary sexual character with two conspicuous extremes and the corresponding variance in female mating preference around no preference may jointly evolve into bimodal distributions with increasing modal divergence of the male and female traits, pulling a population apart into two prezygotically isolated populations. This mode of speciation, driven by two runaway processes in different directions, is promoted by an increase in the efficiency of females in discriminating among males or a decrease in the cost of male conspicuousness, indicating that sympatric speciation may occur more readily if barrier-free or predator-free conditions arise. Although even a slight cost of female preference would cancel the runaway process of sexual selection, it would not cancel the divergent runaway processes of sympatric speciation.     

Reduced adaptation of a non-recombining neo-Y chromosome

Sex chromosomes are generally believed to have descended from a pair of homologous autosomes. Suppression of recombination between the ancestral sex chromosomes led to the genetic degeneration of the Y chromosome. In response, the X chromosome may become dosage-compensated. Most proposed mechanisms for the degeneration of Y chromosomes involve the rapid fixation of deleterious mutations on the Y. Alternatively, Y-chromosome degeneration might be a response to a slower rate of adaptive evolution, caused by its lack of recombination. Here we report patterns of DNA polymorphism and divergence at four genes located on the neo-sex chromosomes of Drosophila miranda. We show that a higher rate of protein sequence evolution of the neo-X-linked copy of Cyclin B relative to the neo-Y copy is driven by positive selection, which is consistent with the adaptive hypothesis for the evolution of the Y chromosome. In contrast, the neo-Y-linked copies of even-skipped and roundabout show an elevated rate of protein evolution relative to their neo-X homologues, probably reflecting the reduced effectiveness of selection against deleterious mutations in a non-recombining genome. Our results provide evidence for the importance of sexual recombination for increasing and maintaining the level of adaptation of a population.     

Adaptive protein evolution in Drosophila

For over 30 years a central question in molecular evolution has been whether natural selection plays a substantial role in evolution at the DNA sequence level. Evidence has accumulated over the last decade that adaptive evolution does occur at the protein level, but it has remained unclear how prevalent adaptive evolution is. Here we present a simple method by which the number of adaptive substitutions can be estimated and apply it to data from Drosophila simulans and D. yakuba. We estimate that 45% of all amino-acid substitutions have been fixed by natural selection, and that on average one adaptive substitution occurs every 45 years in these species.     

Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster.

Two genomic regions with unusually low recombination rates in Drosophila melanogaster have normal levels of divergence but greatly reduced nucleotide diversity, apparently resulting from the fixation of advantageous mutations and the associated hitch-hiking effect. Here we show that for 20 gene regions from across the genome, the amount of nucleotide diversity in natural populations of D. melanogaster is positively correlated with the regional rate of recombination. This cannot be explained by variation in mutation rates and/or functional constraint, because we observe no correlation between recombination rates and DNA sequence divergence between D. melanogaster and its sibling species, D. simulans. We suggest that the correlation may result from genetic hitch-hiking associated with the fixation of advantageous mutants. Hitch-hiking thus seems to occur over a large fraction of the Drosophila genome and may constitute a major constraint on levels of genetic variation in nature.     

Insights into hominid evolution from the gorilla genome sequence

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.     

Positive selection at sites of multiple amino acid replacements since rat-mouse divergence

New alleles become fixed owing to random drift of nearly neutral mutations or to positive selection of substantially advantageous mutations. After decades of debate, the fraction of fixations driven by selection remains uncertain. Within 9,390 genes, we analysed 28,196 codons at which rat and mouse differ from each other at two nucleotide sites and 1,982 codons with three differences. At codons where rat-mouse divergence involved two non-synonymous substitutions, both of them occurred in the same lineage, either rat or mouse, in 64% of cases; however, independent substitutions would occur in the same lineage with a probability of only 50%. All three non-synonymous substitutions occurred in the same lineage for 46% of codons, instead of the 25% expected. Furthermore, comparison of 12 pairs of prokaryotic genomes also shows clumping of multiple non-synonymous substitutions in the same lineage. This pattern cannot be explained by correlated mutation or episodes of relaxed negative selection, but instead indicates that positive selection acts at many sites of rapid, successive amino acid replacement.     

Sequence and analysis of rice chromosome 4

Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.     

Origin and evolution of new exons in the rodent zinc finger protein 39 gene

The origin of new structures and functions is an important process in evolution. In the past decades, we have obtained some preliminary knowledge of the origin and evolution of new genes. However, as the basic unit of genes, the origin and evolution of exons remain unclear. Because young exons retain the footprints of origination, they can be good materials for studying origin and evolution of new exons. In this paper, we report two young exons in a zinc finger protein gene of rodents. Since they are unique sequences in mouse and rat genome and no homologous sequences were found in the orthologous genes of human and pig, the young exons might originate after the divergence of primates and rodents through exonization of intronic sequences. Strong positive selection was detected in the new exons between mouse and rat, suggesting that these exons have undergone significant functional divergence after the separation of the two species. On the other hand, population genetics data of mouse demonstrate that the new exons have been subject to functional constraint, indicating an important function of the new exons in mouse. Functional analyses suggest that these new exons encode a nuclear localization signal peptide, which may mediate new ways of nuclear protein transport. To our knowledge, this is the first example of the origin and evolution of young exons.