High variability and non-neutral evolution of the mammalian avpr1a gene

BACKGROUND: The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in Microtus voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus. RESULTS: We detected high sequence diversity between higher mammalian taxa as well as between species of the genus Microtus. This includes length variation and radical amino acid changes, as well as the presence of distinct protein variants within individuals. Additionally, negative selection prevails on most parts of the first exon of the arginine-vasopressin receptor 1a (avpr1a) gene but it contains regions with higher rates of change that harbour positively selected sites. Synonymous and non-synonymous substitution rates in the avpr1a gene are not exceptional compared to other genes, but they exceed those found in related hormone receptors with similar functions. DISCUSSION: These results stress the importance of considering variation in the coding sequence of avpr1a in regards to associations with life history traits (e.g. social behaviour, mating system, habitat requirements) of voles, other mammals and humans in particular.

Correcting for the bias due to expression specificity improves the estimation of constrained evolution of expression between mouse and human.

MOTIVATION: Comparative analyses of gene expression data from different species have become an important component of the study of molecular evolution. Thus methods are needed to estimate evolutionary distances between expression profiles, as well as a neutral reference to estimate selective pressure. Divergence between expression profiles of homologous genes is often calculated with Pearson's or Euclidean distance. Neutral divergence is usually inferred from randomized data. Despite being widely used, neither of these two steps has been well studied. Here, we analyze these methods formally and on real data, highlight their limitations and propose improvements. RESULTS: It has been demonstrated that Pearson's distance, in contrast to Euclidean distance, leads to underestimation of the expression similarity between homologous genes with a conserved uniform pattern of expression. Here, we first extend this study to genes with conserved, but specific pattern of expression. Surprisingly, we find that both Pearson's and Euclidean distances used as a measure of expression similarity between genes depend on the expression specificity of those genes. We also show that the Euclidean distance depends strongly on data normalization. Next, we show that the randomization procedure that is widely used to estimate the rate of neutral evolution is biased when broadly expressed genes are abundant in the data. To overcome this problem, we propose a novel randomization procedure that is unbiased with respect to expression profiles present in the datasets. Applying our method to the mouse and human gene expression data suggests significant gene expression conservation between these species. CONTACT: marc.robinson-rechavi@unil.ch; sven.bergmann@unil.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Tissue-Specific Evolution of Protein Coding Genes in Human and Mouse.

Protein-coding genes evolve at different rates, and the influence of different parameters, from gene size to expression level, has been extensively studied. While in yeast gene expression level is the major causal factor of gene evolutionary rate, the situation is more complex in animals. Here we investigate these relations further, especially taking in account gene expression in different organs as well as indirect correlations between parameters. We used RNA-seq data from two large datasets, covering 22 mouse tissues and 27 human tissues. Over all tissues, evolutionary rate only correlates weakly with levels and breadth of expression. The strongest explanatory factors of purifying selection are GC content, expression in many developmental stages, and expression in brain tissues. While the main component of evolutionary rate is purifying selection, we also find tissue-specific patterns for sites under neutral evolution and for positive selection. We observe fast evolution of genes expressed in testis, but also in other tissues, notably liver, which are explained by weak purifying selection rather than by positive selection.

Absence of the HLA-G*0113N allele in Amerindian populations from the Brazilian Amazon region

The HLA-G gene is predominantly expressed at the maternal-fetal interface and has been associated with maternal-fetal tolerance. The HLA-G*0113N is a null allele defined by the insertion of a premature stop codon at exon 2, observed in a single Ghanaian individual. Likewise the G*0105N allele, the occurrence of the HL4-G*0113N in a population from an area with high pathogen load suggests that the reduced HLA-G expression in G*0113N heterozygous placentas could improve the intrauterine defense against infections. The presence of the G*0113N allele here was investigated in 150 Amerindians from five isolated tribes that inhabit the Central Amazon and in 295 admixed individuals from the State of Sao Paulo, Southeastern Brazil, previously genotyped for HLA-G. No copy of the G*0113N null allele was found in both population samples by exon 2 sequence-based analysis, reinforcing its restricted occurrence in Africa. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

THE USE OF SIMULATIONS IN EVOLUTIONARY POPULATION GENETICS: APPLICATIONS ON HUMANS, OWLS AND VIRTUAL ORGANISMS

Summary (in English) Computer simulations provide a practical way to address scientific questions that would be otherwise intractable. In evolutionary biology, and in population genetics in particular, the investigation of evolutionary processes frequently involves the implementation of complex models, making simulations a particularly valuable tool in the area. In this thesis work, I explored three questions involving the geographical range expansion of populations, taking advantage of spatially explicit simulations coupled with approximate Bayesian computation. First, the neutral evolutionary history of the human spread around the world was investigated, leading to a surprisingly simple model: A straightforward diffusion process of migrations from east Africa throughout a world map with homogeneous landmasses replicated to very large extent the complex patterns observed in real human populations, suggesting a more continuous (as opposed to structured) view of the distribution of modern human genetic diversity, which may play a better role as a base model for further studies. Second, the postglacial evolution of the European barn owl, with the formation of a remarkable coat-color cline, was inspected with two rounds of simulations: (i) determine the demographic background history and (ii) test the probability of a phenotypic cline, like the one observed in the natural populations, to appear without natural selection. We verified that the modern barn owl population originated from a single Iberian refugium and that they formed their color cline, not due to neutral evolution, but with the necessary participation of selection. The third and last part of this thesis refers to a simulation-only study inspired by the barn owl case above. In this chapter, we showed that selection is, indeed, effective during range expansions and that it leaves a distinguished signature, which can then be used to detect and measure natural selection in range-expanding populations. Résumé (en français) Les simulations fournissent un moyen pratique pour répondre à des questions scientifiques qui seraient inabordable autrement. En génétique des populations, l'étude des processus évolutifs implique souvent la mise en oeuvre de modèles complexes, et les simulations sont un outil particulièrement précieux dans ce domaine. Dans cette thèse, j'ai exploré trois questions en utilisant des simulations spatialement explicites dans un cadre de calculs Bayésiens approximés (approximate Bayesian computation : ABC). Tout d'abord, l'histoire de la colonisation humaine mondiale et de l'évolution de parties neutres du génome a été étudiée grâce à un modèle étonnement simple. Un processus de diffusion des migrants de l'Afrique orientale à travers un monde avec des masses terrestres homogènes a reproduit, dans une très large mesure, les signatures génétiques complexes observées dans les populations humaines réelles. Un tel modèle continu (opposé à un modèle structuré en populations) pourrait être très utile comme modèle de base dans l'étude de génétique humaine à l'avenir. Deuxièmement, l'évolution postglaciaire d'un gradient de couleur chez l'Effraie des clocher (Tyto alba) Européenne, a été examiné avec deux séries de simulations pour : (i) déterminer l'histoire démographique de base et (ii) tester la probabilité qu'un gradient phénotypique, tel qu'observé dans les populations naturelles puisse apparaître sans sélection naturelle. Nous avons montré que la population actuelle des chouettes est sortie d'un unique refuge ibérique et que le gradient de couleur ne peux pas s'être formé de manière neutre (sans l'action de la sélection naturelle). La troisième partie de cette thèse se réfère à une étude par simulations inspirée par l'étude de l'Effraie. Dans ce dernier chapitre, nous avons montré que la sélection est, en effet, aussi efficace dans les cas d'expansion d'aire de distribution et qu'elle laisse une signature unique, qui peut être utilisée pour la détecter et estimer sa force.

Evolutionary simulations to detect functional lineage-specific genes.

MOTIVATION: Supporting the functionality of recent duplicate gene copies is usually difficult, owing to high sequence similarity between duplicate counterparts and shallow phylogenies, which hamper both the statistical and experimental inference. RESULTS: We developed an integrated evolutionary approach to identify functional duplicate gene copies and other lineage-specific genes. By repeatedly simulating neutral evolution, our method estimates the probability that an ORF was selectively conserved and is therefore likely to represent a bona fide coding region. In parallel, our method tests whether the accumulation of non-synonymous substitutions reveals signatures of selective constraint. We show that our approach has high power to identify functional lineage-specific genes using simulated and real data. For example, a coding region of average length (approximately 1400 bp), restricted to hominoids, can be predicted to be functional in approximately 94-100% of cases. Notably, the method may support functionality for instances where classical selection tests based on the ratio of non-synonymous to synonymous substitutions fail to reveal signatures of selection. Our method is available as an automated tool, ReEVOLVER, which will also be useful to systematically detect functional lineage-specific genes of closely related species on a large scale. AVAILABILITY: ReEVOLVER is available at http://www.unil.ch/cig/page7858.html.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori.

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipα) and hitherto unknown functional genes.

The molecular mechanisms and evolutionary significance of plumage colour variation in pied flycatchers (Ficedula hypoleuca)

A common feature of natural populations is that individuals differ in morphology, physiologyand behavior (i.e .phenotype). A thorough understanding of the molecular mechanisms and evolutionary forces behind this phenotypic variation is a prerequisite for understanding evolution.This thesis examines the molecular mechanism and the roles of the different evolutionary forces in plumage colour variation in pied flycatchers (Ficedulahypoleuca). Malepied flycatchers exhibit marked variation in both pigmentary and structural plumage colourand the trait has repeatedly been suggested to be of adaptive significance. An examination of plumage colour variation on reproductive output trevealed that structural colouration, and more specifically the degree of ultraviolet (UV) reflectance had an effect on number of young sired. Paternity analyses of breeding males revealed that males that had been cuckolded by their social mate tended to be less UV reflectant than males that had not been cuckolded.Neither pigment-based norstructural colouration was found to affect the probability of siring young in other nests. Phenotypic differentiation was found to be markedly greater than differentiation at neutralgenetic markers across the pied flycatcher breeding range. Furthermore patterns of differentiationin phenotypes and selectively neutral genes were not uniform. Outlier tests searching for genomic footprints of selection revealed elevated levels of genetic divergence in a gene associated with feather development (and thus potentially structural colouration) and ultraviolet vision. Th eobserved differentiation in allelic frequencies was particularly pronounced in the Spanish piedflycatcher populations. Examining gene expression during feather development indicated that the TYRP1 gene (known to be involved in the production of black pigment) may be relevant in generating phenotypic variation in pied flycatcher plumage. Also, energy homeostasis related genesfeatured prominently among the genes found to be expressed in one extreme phenotype but not the other. This is of particular interest in light of what is known about the pleiotropy ofthe melanocortin system which underlies brown-black pigment production. The melanocortinsystem is also associated with energy homeostasis (among a number of other physiological functions) and thus the results could be pointing to the signalling function of brown-blackplumage. Plumage colour variation in pied flycatchers, both structural and pigmentary, can thus beconcluded to be exhibiting signals of non-neutral evolution. Structural colouration was found to play a role in sexual selection and putative signals of selection were further detected in acandidate gene for this trait. Evidence for non-neutral evolution of pigmentary colouration was also detected. These findings, together with the fact that preliminary evidence for an energy balance associated signalling function for plumage was found, present good starting points for further investigations into the meaning and mechanisms of plumage colour variation in piedflycatchers.

Autocorrelação espacial das freqüências alélicas em subpopulações de cagaiteira (Eugenia dysenterica DC., Myrtaceae) no sudeste de Goiás

Dentre as diversas árvores frutíferas nativas dos cerrados, a cagaiteira (Eugenia dysenterica DC.) merece destaque pelo seu amplo potencial econômico. A fim de fornecer algumas informações relativas ao padrão espacial da variabilidade genética desta espécie, foram realizadas análises de autocorrelação espacial das freqüências alélicas em dez subpopulações locais da região sudeste do Estado de Goiás. Foram utilizados marcadores isoenzimáticos, em um total de seis sistemas enzimáticos (SKDH, 6-PGD, alfa-EST, MDH, PGI e PGM), com oito locos polimórficos. Foi realizada uma análise de autocorrelação espacial, utilizando índices I de Moran estimados em quatro classes de distância geográfica. Os correlogramas mostraram que, de fato, a divergência genética está estruturada no espaço em um padrão clinal de variação. Simulações de evolução neutra da variação nas freqüências alélicas entre as subpopulações, geradas a partir de um processo Ornstein-Uhlenbeck (O-U), foram utilizadas para avaliar os padrões espaciais sob essa hipótese e compará-los com os correlogramas obtidos com as freqüências alélicas. As análises indicaram que um processo estocástico (evolução neutra) deve ser o responsável pela diferenciação genética dessas populações, havendo assim um balanço entre fluxo gênico em pequenas distâncias geográficas e deriva genética dentro das populações locais, como o esperado para modelos de isolamento-por-distância ou "stepping-stone".

Genomic signatures of evolutionary transitions from solitary to group living

The evolution of eusociality is one of the major transitions in evolution, but the underlying genomic changes are unknown. We compared the genomes of 10 bee species that vary in social complexity, representing multiple independent transitions in social evolution, and report three major findings. First, many important genes show evidence of neutral evolution as a consequence of relaxed selection with increasing social complexity. Second, there is no single road map to eusociality; independent evolutionary transitions in sociality have independent genetic underpinnings. Third, though clearly independent in detail, these transitions do have similar general features, including an increase in constrained protein evolution accompanied by increases in the potential for gene regulation and decreases in diversity and abundance of transposable elements. Eusociality may arise through different mechanisms each time, but would likely always involve an increase in the complexity of gene networks.

Genetic variability in mitochondrial and nuclear genes of Larus dominicanus (Charadriiformes, Laridae) from the Brazilian coast

Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull populations on the Brazilian coast and compared this variability with that of sub-Antarctic island populations of this species. Kelp Gulls showed extremely low genetic variability for nnitochondrial markers (cytb and ATPase) and high diversity for a nuclear locus (intron 7 of the beta-fibrinogen). The intraspecific evolutionary history of Kelp Gulls showed that the variability found in intron 7 of the beta-fibrinogen gene was compatible with the variability expected under neutral evolution but suggested an increase in population size during the last 10,000 years. However, none of the markers revealed evidence of a bottleneck population. These findings indicate that the recent origin of Kelp Gulls is the main explanation for their nuclear diversity, although selective pressure on the mtDNA of this species cannot be discarded.

In silico identification and characterisation of 17 polymorphic anonymous non-coding sequence markers (ANMs) for red grouse (Lagopus lagopus scotica)

Peer reviewed

Evidence of neutral transcriptome evolution in plants

The transcriptome of an organism is its set of gene transcripts (mRNAs) at a defined spatial and temporal locus. Because gene expression is affected markedly by environmental and developmental perturbations, it is widely assumed that transcriptome divergence among taxa represents adaptive phenotypic selection. This assumption has been challenged by neutral theories which propose that stochastic processes drive transcriptome evolution. To test for evidence of neutral transcriptome evolution in plants, we quantified 18 494 gene transcripts in nonsenescent leaves of 14 taxa of Brassicaceae using robust cross-species transcriptomics which includes a two-step physical and in silico-based normalization procedure based on DNA similarity among taxa. Transcriptome divergence correlates positively with evolutionary distance between taxa and with variation in gene expression among samples. Results are similar for pseudogenes and chloroplast genes evolving at different rates. Remarkably, variation in transcript abundance among root-cell samples correlates positively with transcriptome divergence among root tissues and among taxa. Because neutral processes affect transcriptome evolution in plants, many differences in gene expression among or within taxa may be nonfunctional, reflecting ancestral plasticity and founder effects. Appropriate null models are required when comparing transcriptomes in space and time.

Electrochemistry of macrocyclic cobalt(III/II) hexaamines: Electrocatalytic hydrogen evolution in aqueous solution

The macrocyclic cobalt hexaamines [Co(trans-diammac)](3+) and [Co(cis-diammac)](3+) (diammac = 6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) are capable of reducing the overpotential for hydrogen evolution on a mercury cathode in aqueous solution. Protons are reduced in a catalytic process involving reoxidation of the Co-II species to its parent Co-III complex. The cycle is robust at neutral pH with no decomposition of catalyst. The stability of the [Co(trans-diammac)](2+) and [Co(cis-diammac)](2+) complexes depends on the pH of the solution and the coordinating properties of the supporting electrolyte. Electrochemical studies indicate that the adsorbed Co-II complex on the surface of mercury is the active catalyst for the reduction of protons to dihydrogen.