Great ape genetic diversity and population history.

Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Exploring the Phenotypic Space and the Evolutionary History of a Natural Mutation in Drosophila melanogaster.

A major challenge of modern Biology is elucidating the functional consequences of natural mutations. Although we have a good understanding of the effects of laboratory-induced mutations on the molecular- and organismal-level phenotypes, the study of natural mutations has lagged behind. In this work, we explore the phenotypic space and the evolutionary history of a previously identified adaptive transposable element insertion. We first combined several tests that capture different signatures of selection to show that there is evidence of positive selection in the regions flanking FBti0019386 insertion. We then explored several phenotypes related to known phenotypic effects of nearby genes, and having plausible connections to fitness variation in nature. We found that flies with FBti0019386 insertion had a shorter developmental time and were more sensitive to stress, which are likely to be the adaptive effect and the cost of selection of this mutation, respectively. Interestingly, these phenotypic effects are not consistent with a role of FBti0019386 in temperate adaptation as has been previously suggested. Indeed, a global analysis of the population frequency of FBti0019386 showed that climatic variables explain well the FBti0019386 frequency patterns only in Australia. Finally, although FBti0019386 insertion could be inducing the formation of heterochromatin by recruiting HP1a (Heterochromatin Protein 1a) protein, the insertion is associated with upregulation of sra in adult females. Overall, our integrative approach allowed us to shed light on the evolutionary history, the relevant fitness effects, and the likely molecular mechanisms of an adaptive mutation and highlights the complexity of natural genetic variants.

DPDB: a database for the storage, representation and analysis of polymorphism in the Drosophila genus.

MOTIVATION: Polymorphism studies are one of the main research areas of this genomic era. To date, however, no comprehensive secondary databases have been designed to provide searchable collections of polymorphic sequences with their associated diversity measures. RESULTS: We define a data model for the storage, representation and analysis of genotypic and haplotypic data. Under this model we have created DPDB, 'Drosophila Polymorphism Database', a web site that provides a daily updated repository of all well-annotated polymorphic sequences in the Drosophila genus. It allows the search for any polymorphic set according to different parameter values of nucleotide diversity, linkage disequilibrium and codon bias. For data collection, analysis and updating we use PDA, a pipeline that automates the process of sequence retrieval, grouping, alignment and estimation of nucleotide diversity from Genbank sequences in different functional regions. The web site also includes analysis tools for sequence comparison and the estimation of genetic diversity, a page with real-time statistics of the database contents, a help section and a collection of selected links. AVAILABILITY: DPDB is freely available at http://dpdb.uab.es and can be downloaded via FTP.

Analysis of Five Gene Sets in Chimpanzees Suggests Decoupling between the Action of Selection on Protein-Coding and on Noncoding Elements.

We set out to investigate potential differences and similarities between the selective forces acting upon the coding and noncoding regions of five different sets of genes defined according to functional and evolutionary criteria: 1) two reference gene sets presenting accelerated and slow rates of protein evolution (the Complement and Actin pathways); 2) a set of genes with evidence of accelerated evolution in at least one of their introns; and 3) two gene sets related to neurological function (Parkinson's and Alzheimer's diseases). To that effect, we combine human-chimpanzee divergence patterns with polymorphism data obtained from target resequencing 20 central chimpanzees, our closest relatives with largest long-term effective population size. By using the distribution of fitness effect-alpha extension of the McDonald-Kreitman test, we reproduce inferences of rates of evolution previously based only on divergence data on both coding and intronic sequences and also obtain inferences for other classes of genomic elements (untranslated regions, promoters, and conserved noncoding sequences). Our results suggest that 1) the distribution of fitness effect-alpha method successfully helps distinguishing different scenarios of accelerated divergence (adaptation or relaxed selective constraints) and 2) the adaptive history of coding and noncoding sequences within the gene sets analyzed is decoupled.

HeT-A_pi1, a piRNA target sequence in the Drosophila telomeric retrotransposon HeT-A, is extremely conserved across copies and species.

The maintenance of the telomeres in Drosophila species depends on the transposition of the non-LTR retrotransposons HeT-A, TAHRE and TART. HeT-A and TART elements have been found in all studied species of Drosophila suggesting that their function has been maintained for more than 60 million years. Of the three elements, HeT-A is by far the main component of D. melanogaster telomeres and, unexpectedly for an element with an essential role in telomere elongation, the conservation of the nucleotide sequence of HeT-A is very low. In order to better understand the function of this telomeric retrotransposon, we studied the degree of conservation along HeT-A copies. We identified a small sequence within the 3' UTR of the element that is extremely conserved among copies of the element both, within D. melanogaster and related species from the melanogaster group. The sequence corresponds to a piRNA target in D. melanogaster that we named HeT-A_pi1. Comparison with piRNA target sequences from other Drosophila retrotransposons showed that HeT-A_pi1 is the piRNA target in the Drosophila genome with the highest degree of conservation among species from the melanogaster group. The high conservation of this piRNA target in contrast with the surrounding sequence, suggests an important function of the HeT-A_pi1 sequence in the co-evolution of the HeT-A retrotransposon and the Drosophila genome.

Protein polymorphism is negatively correlated with conservation of intronic sequences and complexity of expression patterns in Drosophila melanogaster.

We report a significant negative correlation between nonsynonymous polymorphism and intron length in Drosophila melanogaster. This correlation is similar to that between protein divergence and intron length previously reported in Drosophila. We show that the relationship can be explained by the content of conserved noncoding sequences (CNS) within introns. In addition, genes with a high regulatory complexity and many genetic interactions also exhibit larger amounts of CNS within their introns and lower values of nonsynonymous polymorphism. The present study provides relevant evidence on the importance of intron content and expression patterns on the levels of coding polymorphism.

Drosophila polymorphism database (DPDB): a portal for nucleotide polymorphism in Drosophila.

As a growing number of haplotypic sequences from resequencing studies are now accumulating for Drosophila in the main primary sequence databases, collectively they can now be used to describe the general pattern of nucleotide variation across species and genes of this genus. The Drosophila Polymorphism Database (DPDB) is a secondary database that provides a collection of all well-annotated polymorphic sequences in Drosophila together with their associated diversity measures and options for reanalysis of the data that greatly facilitate both multi-locus and multi-species diversity studies in one of the most important groups of model organisms. Here we describe the state-of-the-art of the DPDB database and provide a step-by-step guide to all its searching and analytic capabilities. Finally, we illustrate its usefulness through selected examples. DPDB is freely available at http://dpdb.uab.cat.