Localizing recent adaptive evolution in the human genome

Identifying genomic locations that have experienced selective sweeps is an important first step toward understanding the molecular basis of adaptive evolution. Using statistical methods that account for the confounding effects of population demography, recombination rate variation, and single-nucleotide polymorphism ascertainment, while also providing fine-scale estimates of the position of the selected site, we analyzed a genomic dataset of 1.2 million human single-nucleotide polymorphisms genotyped in African-American, European-American, and Chinese samples. We identify 101 regions of the human genome with very strong evidence (p < 10⁻⁵) of a recent selective sweep and where our estimate of the position of the selective sweep falls within 100 kb of a known gene. Within these regions, genes of biological interest include genes in pigmentation pathways, components of the dystrophin protein complex, clusters of olfactory receptors, genes involved in nervous system development and function, immune system genes, and heat shock genes. We also observe consistent evidence of selective sweeps in centromeric regions. In general, we find that recent adaptation is strikingly pervasive in the human genome, with as much as 10% of the genome affected by linkage to a selective sweep.     

Compositional evolution of noncoding DNA in the human and chimpanzee genomes

We have examined the compositional evolution of noncoding DNA in the primate genome by comparison of lineage-specific substitutions observed in 1.8 Mb of genomic alignments of human, chimpanzee, and baboon with 6542 human single-nucleotide polymorphisms (SNPs) rooted using chimpanzee sequence. The pattern of compositional evolution, measured in terms of the numbers of GC-->AT and AT-->GC changes, differs significantly between fixed and polymorphic sites, and indicates that there is a bias toward fixation of AT-->GC mutations, which could result from weak directional selection or biased gene conversion in favor of high GC content. Comparison of the frequency distributions of a subset of the SNPs revealed no significant difference between GC-->AT and AT-->GC polymorphisms, although AT-->GC polymorphisms in regions of high GC segregate at slightly higher frequencies on average than GC-->AT polymorphisms, which is consistent with a fixation bias favoring high GC in these regions. However, the substitution data suggest that this fixation bias is relatively weak, because the compositional structure of the human and chimpanzee genomes is becoming homogenized, with regions of high GC decreasing in GC content and regions of low GC increasing in GC content. The rate and pattern of nucleotide substitution in 333 Alu repeats within the human-chimpanzee-baboon alignments are not significantly affected by the GC content of the region in which they are inserted, providing further evidence that, since the time of the human-chimpanzee ancestor, there has been little or no regional variation in mutation bias.     

Molecular evolution of genes in avian genomes

Background

Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologs of chicken, zebra finch, a lizard and three mammalian species.

Results

We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an over-representation of several functional classes, including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton.

Conclusions

Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes, including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between ω and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes.     

Chromosome-level genomes provide insights into genome evolution,organization and size in Epichloe fungi

Epichloe fungi are endophytes of cool season grasses, both wild species and commercial cultivars, where they may exhibit mutualistic or pathogenic lifestyles. The Epichloe-grass symbiosis is of great interest to agricultural research for the fungal bioprotective properties conferred to host grasses but also serves as an ideal system to study the evolution of fungal plant-pathogens in natural environments. Here, we assembled and annotated gapless chromosome-level genomes of two pathogenic Epichloe sibling species. Both genomes have a bipartite genome organization, with blocks of highly syntenic gene-rich regions separated by blocks of AT-rich DNA. The AT-rich regions show an extensive signature of RIP (repeat-induced point mutation) and the expansion of this compartment accounts for the large difference in genome size between the two species. This study reveals how the rapid evolution of repeat structure can drive divergence between closely related taxa and highlights the evolutionary role of dynamic compartments in fungal genomes.     

DNA sequence organisation in avian genomes

By means of renaturation kinetics of DNA of the three avian species Cairina domestica, Gallus domesticus and Columba livia domestica the following major DNA repetition classes were observed: a very fast reannealing fraction comprising about 15% of the DNA, a fast or intermediate reannealing fraction that makes up 10%, and a slow reannealing fraction of about 70%, which apparently renatures with single copy properties. — Comparing the reassociation behaviour of short (0.3 kb) and long (>2 kb) DNA fragments of duck and chicken it becomes apparent that only 12% (duck) and 28% (chicken) of the single copy DNA are interspersed with repetitive elements on 2 to 3 kb long fragments. The lengths of the repetitive sequences were estimated by optical hyperchromicity measurements, by agarose A-50 chromatography of S₁ nuclease resistant duplexes and by electron microscopic measurements of the S₁ nuclease resistant duplexes. It was found that in the case of the chicken DNA the single copy sequences alternating with middle repetitive ones are at least 2.3 kb long; the interspersed moderate repeats have a length average of at least 1.5 kb. The sequence length of the moderate repeats in duck DNA is smaller. The results show that the duck and the chicken genomes do not follow the short period interspersion pattern of genome organisation, characteristic of the eucaryotic organisms studied so far.     

Reconstruction of gross avian genome structure,organization and evolution suggests that the chicken lineage most closely resembles the dinosaur avian ancestor

Background

The availability of multiple avian genome sequence assemblies greatly improves our ability to define overall genome organization and reconstruct evolutionary changes. In birds, this has previously been impeded by a near intractable karyotype and relied almost exclusively on comparative molecular cytogenetics of only the largest chromosomes. Here, novel whole genome sequence information from 21 avian genome sequences (most newly assembled) made available on an interactive browser (Evolution Highway) was analyzed.

Results

Focusing on the six best-assembled genomes allowed us to assemble a putative karyotype of the dinosaur ancestor for each chromosome. Reconstructing evolutionary events that led to each species’ genome organization, we determined that the fastest rate of change occurred in the zebra finch and budgerigar, consistent with rapid speciation events in the Passeriformes and Psittaciformes. Intra- and interchromosomal changes were explained most parsimoniously by a series of inversions and translocations respectively, with breakpoint reuse being commonplace. Analyzing chicken and zebra finch, we found little evidence to support the hypothesis of an association of evolutionary breakpoint regions with recombination hotspots but some evidence to support the hypothesis that microchromosomes largely represent conserved blocks of synteny in the majority of the 21 species analyzed. All but one species showed the expected number of microchromosomal rearrangements predicted by the haploid chromosome count. Ostrich, however, appeared to retain an overall karyotype structure of 2n = 80 despite undergoing a large number (26) of hitherto un-described interchromosomal changes.

Conclusions

Results suggest that mechanisms exist to preserve a static overall avian karyotype/genomic structure, including the microchromosomes, with widespread interchromosomal change occurring rarely (e.g., in ostrich and budgerigar lineages). Of the species analyzed, the chicken lineage appeared to have undergone the fewest changes compared to the dinosaur ancestor.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1060) contains supplementary material, which is available to authorized users.     

DNA of avian myeloblastosis-associated virus type 2 integrates at multiple sites in the chicken genome.

The cellular sites of integration of the avian myeloblastosis-associated virus type 2 (MAV-2) DNA have been examined by Southern blot analysis of cellular DNA from infected cloned and uncloned chicken embryonic fibroblasts. Provirus-cell juncture fragments were not detected in restriction enzyme digests of DNA from MAV-2-infected uncloned cells. However, each MAV-2-infected cell clone examined produced a unique set of junctive bands. Thse findings indicate that multiple sites of integration exists for MAV-2 proviruses in cellular DNA.     

Female-specific DNA sequences in the chicken genome

Eight in silico W-specific sequences from the WASHUC1 chicken genome assembly gave female-specific PCR products using chicken DNA. Some of these fragments gave female-specific products with turkey and peacock DNA. Sequence analysis of these 8 fragments (3077 bp total) failed to detect any polymorphisms among 10 divergent chickens. In contrast, comparison of the DNA sequences of chicken with those of turkey and peacock revealed a nucleotide difference every 25 and 28 bp, respectively. Radiation hybrid mapping verified that these amplicons exist only on chromosome W. The homology of 6 W-specific fragments with chromo-helicase-DNA-binding gene and expressed sequenced tags from chicken and other species indicate that these fragments may have or have had a biological function. These fragments may be used for early sexing in commercial chicken and turkey flocks.     

The genomics of long tandem arrays of satellite DNA in the human genome

At least 10% of DNA in the human genome consists of long arrays of repeated sequences, arranged in tandem head-to-tail arrays in a number of discrete, highly localized chromosomal regions. Different families of these so-called "satellite DNA" sequences have been defined, organized in diverged subsets on different chromosomes. The molecular, cytogenetic, and evolutionary analysis of the hierarchical organization of such sequences in the human and other complex genomes encompasses a variety of approaches, including chromosomal mapping, in situ hybridization, genetic linkage analysis, long-range restriction mapping, and DNA sequencing. Investigation of the organization of satellite arrays constitutes a necessary first step towards eventual elucidation of the origin, evolution, and maintenance of these sequences and their contribution to the structure and behavior of human chromosomes.     

Minisatellite DNA markers in the chicken genome

This paper reports the detailed characterization of multilocus minisatellite DNA fingerprints in the chicken. Results are presented of DNA fingerprint segregation analyses carried out in three chicken pedigrees, calculating the number of detected loci, testing for Mendelian inheritance, and cosegregation among fingerprint bands. Two pedigrees (families 1 and 2) were analysed using the Jeffreys probes 33.6 and 33.15 only, and one pedigree (family 3) was analysed using 33.6, 33.15. 3′α-globin HVR and M13 protein III gene repeat. Mean band transmission frequencies in families 1 and 2 were near to the Mendelian expectation of 0.5 and no mutations were observed. Family 3 showed transmission frequencies slightly exceeding 0.5. Linkage among bands was higher than observed in some other avian species, with each allele represented by a mean of 1.48 HaeIII fragments. Cosegregation of heterozygous parental fragments representing distinguishable loci followed the expected binomial distribution. The number of minisatellites detectable by the four probes was estimated to be 217. The pattern of cosegregation among those minisatellite loci was tested against that expected for different levels of recombination through the use of a simulation model. We conclude that most minisatellites are unlinked and probably widely dispersed in the chicken genome.     

Stress-induced modulators of repeat instability and genome evolution

Evolution hinges on the ability of organisms to adapt to their environment. A key regulator of adaptability is mutation rate, which must be balanced to maintain genome fidelity while permitting sufficient plasticity to cope with environmental changes. Multiple mechanisms govern an organism's mutation rate. Constitutive mechanisms include mutator alleles that drive global, permanent increases in mutation rates, but these changes are confined to the subpopulation that carries the mutator allele. Other mechanisms focus mutagenesis in time and space to improve the chances that adaptive mutations can spread through the population. For example, environmental stress can induce mechanisms that transiently relax the fidelity of DNA repair to bring about a temporary increase in mutation rates during times when an organism experiences a reduced fitness for its surroundings, as has been demonstrated for double-strand break repair in Escherichia coli. Still, other mechanisms control the spatial distribution of mutations by directing changes to especially mutable sequences in the genome. In eukaryotic cells, for example, the stress-sensitive chaperone Hsp90 can regulate the length of trinucleotide repeats to fine-tune gene function and can regulate the mobility of transposable elements to enable larger functional changes. Here, we review the regulation of mutation rate, with special emphasis on the roles of tandem repeats and environmental stress in genome evolution.     

Cell size does not always correspond to genome size: phylogenetic analysis in geckos questions optimal DNA theories of genome size evolution

At higher taxonomic levels, a significant correlation between genome size (GS) and erythrocyte size (ES) has been reported for many taxa. Under optimal DNA theories, several mechanisms presuming a causative link between GS and ES have been proposed to explain this seemingly general pattern. The correlation between GS and ES has been rarely tested among closely related organisms within an explicit phylogenetic framework. Eyelid geckos (family Eublepharidae) serve as a proper group to conduct such an analysis. We used flow cytometry to measure GS in 15 forms of eublepharids and conducted a phylogenetic reconstruction of GS and ES to test the successiveness of evolutionary shifts in these traits. Most parsimoniously, there were two independent increases and two decreases in GS during the evolution of eublepharids. Nevertheless, changes in GS and ES were not phylogenetically associated in a manner predicted by optimal DNA theories. Our results question the generality of causative bonds between DNA content and cell size and demonstrate that cell size cannot always serve as a proxy of GS. We suggest there is no need to expect a direct causative link between GS and ES to explain the correlation between GS and cell size at higher taxonomic levels. Such a correlation can be explained by simple mechanistic constraints and a combination of the population-genetic model of genome complexity with cell-size-metabolic rate relationship.     

Pentatricopeptide repeat proteins constrain genome evolution in chloroplasts

Higher plants encode hundreds of pentatricopeptide repeat proteins (PPRs) that are involved in several types of RNA processing reactions. Most PPR genes are predicted to be targeted to chloroplasts or mitochondria, and many are known to affect organellar gene expression. In some cases, RNA binding has been directly demonstrated, and the sequences of the cis-elements are known. In this work, we demonstrate that RNA cis-elements recognized by PPRs are constrained in chloroplast genome evolution. Cis-elements for two PPR genes and several RNA editing sites were analyzed for sequence changes by pairwise nucleotide substitution frequency, pairwise indel frequency, and maximum likelihood (ML) phylogenetic distances. All three of these analyses demonstrated that sequences within the cis-element are highly conserved compared with surrounding sequences. In addition, we have compared sequences around chloroplast editing sites and homologous sequences in species that lack an editing site due to the presence of a genomic T. Cis-elements for RNA editing sites are highly conserved in angiosperms; by contrast, comparable sequences around a genomically encoded T exhibit higher rates of nucleotide substitution, higher frequencies of indels, and greater ML distances. The loss in requirement for editing to create the ndhD start codon has resulted in the conversion of the PPR gene responsible for editing that site to a pseudogene. We show that organellar dependence on nuclear-encoded PPR proteins for gene expression has constrained the evolution of cis-elements that are required at the level of RNA processing. Thus, the expansion of the PPR gene family in plants has had a dramatic effect on the evolution of plant organelle genomes.     

Punctuated genome size evolution in Liliaceae

Most angiosperms possess small genomes (mode 1C = 0.6 pg, median 1C = 2.9 pg). Those with truly enormous genomes (i.e. > or = 35 pg) are phylogenetically restricted to a few families and include Liliaceae - with species possessing some of the largest genomes so far reported for any plant as well as including species with much smaller genomes. To gain insights into when and where genome size expansion took place during the evolution of Liliaceae and the mode and tempo of this change, data for 78 species were superimposed onto a phylogenetic tree and analysed. Results suggest that genome size in Liliaceae followed a punctuated rather than gradual mode of evolution and that most of the diversification evolved recently rather than early in the evolution of the family. We consider that the large genome sizes of Liliaceae may have emerged passively rather than being driven primarily by selection.     

The interspersed DNA repeat conserved in water birds' genomes

A putative old and ubiquitous interspersed DNA repeat family was identified from TaqI restriction, M13 cloning, and sequencing of the genomic DNA of a Mallard (Anas platyrhynchos), a Muscovy Duck (Cairina moschata), a Toulouse Goose (Anser anser), and a Black Swan (Cygnus atratus). A 425-bp consensus core sequence was obtained for the interspersed family. The 425-bp unit was about 2% of the avian genome and was found to be conserved in at least four genera of the order Anseriforme: Anas, Anser, Cairina, and Cygnus.     

The evolution of genome size in ants

Background  

Despite the economic and ecological importance of ants, genomic tools for this family (Formicidae) remain woefully scarce. Knowledge of genome size, for example, is a useful and necessary prerequisite for the development of many genomic resources, yet it has been reported for only one ant species (Solenopsis invicta), and the two published estimates for this species differ by 146.7 Mb (0.15 pg).