Biomedical subjects

Julio Rozas

Publications and source records attributed to Julio Rozas.

11 recordsLinked to original sources

PubMed2006

Unexpected high polymorphism at the FABP4 gene unveils a complex history for pig populations.

Fatty acid bing protein 4 (FABP4) plays a key role in fat regulation in mammals and is a strong positional candidate gene for the FAT1 quantitative trait locus located on porcine chromosome 4. DNA resequencing of the FABP4 gene region in 23 pigs from 10 breeds and wild boar revealed 134 variants in 6.4 kb, representing a silent nucleotide diversity of piS=0.01, much higher than reported so far in animal domestic species. Moreover, this diversity was highly structured. Also strikingly, the FABP4 phylogenetic tree did not show any geographical or breed origin clustering, with distant breeds sharing similar haplotypes and some of the most heterozygous samples pertaining to highly inbred animals like Iberian Guadyerbas (inbreeding coefficient approximately 0.3) or British Tamworth. In contrast, the cytochrome b (mtDNA) phylogenetic tree was coherent with geographical origin. The estimated age of the most recent common ancestor for the most divergent Iberian or Tamworth haplotypes was much older than domestication. An additional panel of 100 pigs from 8 different breeds and wild boar from Spain, Tunisia, Sardinia, and Japan was genotyped for seven selected single nucleotide polymorphisms and shows that high variability at the porcine FABP4 is the rule rather than the exception. Pig populations, even highly inbred, can maintain high levels of variability for surprisingly long periods of time.

Animals↗

PubMed2006

Genome-wide DNA polymorphism analyses using VariScan.

BACKGROUND: DNA sequence polymorphisms analysis can provide valuable information on the evolutionary forces shaping nucleotide variation, and provides an insight into the functional significance of genomic regions. The recent ongoing genome projects will radically improve our capabilities to detect specific genomic regions shaped by natural selection. Current available methods and software, however, are unsatisfactory for such genome-wide analysis. RESULTS: We have developed methods for the analysis of DNA sequence polymorphisms at the genome-wide scale. These methods, which have been tested on a coalescent-simulated and actual data files from mouse and human, have been implemented in the VariScan software package version 2.0. Additionally, we have also incorporated a graphical-user interface. The main features of this software are: i) exhaustive population-genetic analyses including those based on the coalescent theory; ii) analysis adapted to the shallow data generated by the high-throughput genome projects; iii) use of genome annotations to conduct a comprehensive analyses separately for different functional regions; iv) identification of relevant genomic regions by the sliding-window and wavelet-multiresolution approaches; v) visualization of the results integrated with current genome annotations in commonly available genome browsers. CONCLUSION: VariScan is a powerful and flexible suite of software for the analysis of DNA polymorphisms. The current version implements new algorithms, methods, and capabilities, providing an important tool for an exhaustive exploratory analysis of genome-wide DNA polymorphism data.

Algorithms↗

PubMed2006

Positive selection versus demography: evolutionary inferences based on an unusual haplotype structure in Drosophila simulans.

Coalescent simulations were used to investigate the possible role of population subdivision and history in shaping nucleotide variation in a recombining 88-kb genomic fragment of Drosophila simulans displaying an unusual large-scale haplotype structure. The multilocus analysis, based on summary statistics using specific demographic null models under recombination, indicates that the observed levels of linkage disequilibrium differed significantly from the values expected under different bottleneck and population admixture scenarios. These results indicate that demography alone may not account for the observed pattern of variation and support the previous claim that the data are better described by a model in which an adaptive mutation has not yet gone to fixation.

Animals↗

PubMed2005

VariScan: Analysis of evolutionary patterns from large-scale DNA sequence polymorphism data.

SUMMARY: VeriScan is a software package for the analysis of DNA sequence polymorphisms at the whole genome scale. Among other features, the software (1) can conduct many population genetic analyses; (2) incorporates a multiresolution wavelet transform-based method that allows capturing relevant information from DNA polymorphism data; (3) facilitates the visualization of the results in the most commonly used genome browsers.

Algorithms↗

PubMed2005

Chromosomal inversion polymorphism leads to extensive genetic structure: a multilocus survey in Drosophila subobscura.

The adaptive character of inversion polymorphism in Drosophila subobscura is well established. The O(ST) and O(3+4) chromosomal arrangements of this species differ by two overlapping inversions that arose independently on O(3) chromosomes. Nucleotide variation in eight gene regions distributed along inversion O(3) was analyzed in 14 O(ST) and 14 O(3+4) lines. Levels of variation within arrangements were quite similar along the inversion. In addition, we detected (i) extensive genetic differentiation between arrangements in all regions, regardless of their distance to the inversion breakpoints; (ii) strong association between nucleotide variants and chromosomal arrangements; and (iii) high levels of linkage disequilibrium in intralocus and also in interlocus comparisons, extending over distances as great as approximately 4 Mb. These results are not consistent with the higher genetic exchange between chromosomal arrangements expected in the central part of an inversion from double-crossover events. Hence, double crossovers were not produced or, alternatively, recombinant chromosomes were eliminated by natural selection to maintain coadapted gene complexes. If the strong genetic differentiation detected along O(3) extends to other inversions, nucleotide variation would be highly structured not only in D. subobscura, but also in the genome of other species with a rich chromosomal polymorphism.

Animals↗

PubMed2003

DnaSP, DNA polymorphism analyses by the coalescent and other methods.

SUMMARY: DnaSP is a software package for the analysis of DNA polymorphism data. Present version introduces several new modules and features which, among other options allow: (1) handling big data sets (approximately 5 Mb per sequence); (2) conducting a large number of coalescent-based tests by Monte Carlo computer simulations; (3) extensive analyses of the genetic differentiation and gene flow among populations; (4) analysing the evolutionary pattern of preferred and unpreferred codons; (5) generating graphical outputs for an easy visualization of results. AVAILABILITY: The software package, including complete documentation and examples, is freely available to academic users from: http://www.ub.es/dnasp

Algorithms↗

PubMed2003

Nucleotide polymorphism in the RpII215 gene region of the insular species Drosophila guanche: reduced efficacy of weak selection on synonymous variation.

An approximately 6.9-kb region encompassing the RpII215 gene was sequenced for 24 individuals of the island endemic species Drosophila guanche. The comparative analysis of synonymous polymorphism and divergence in D. guanche and D. subobscura, two species with pronounced differences in population size, allows contrasting the nearly neutral character of synonymous mutations. In D. guanche, unlike in D. subobscura, (1) the ratio of preferred to unpreferred synonymous changes was similar for polymorphic and fixed changes, (2) the numbers of preferred and unpreferred changes, both polymorphic and fixed, could be explained by the mutational process, and (3) the estimated scaled selection coefficient for unpreferred mutations did not differ significantly from zero. Additionally, the comparative analysis revealed that both the ratio of preferred to unpreferred synonymous changes and the frequency spectrum of unpreferred polymorphic mutations differed significantly between species. All these results indicate that a large fraction of synonymous mutations in the RpII215 gene behave as effectively neutral in D. guanche, whereas they are weakly selected in D. subobscura. The reduced efficacy of selection in the insular species constitutes strong evidence of the nearly neutral character of synonymous mutations and, therefore, of the role of weak selection in maintaining codon bias.

Animals↗

PubMed2003

Large-scale adaptive hitchhiking upon high recombination in Drosophila simulans.

Natural selection is expected to leave a characteristic footprint on neighboring nucleotide variation through the effects of genetic linkage. The size of the region affected is proportional to the strength of selection and greatly reduced with the recombinational distance from the selected site. Thus, the genomic footprint of selection is generally believed to be restricted to a small DNA stretch in normal and highly recombining regions. Here, we study the effect of selection on linked polymorphism (hitchhiking effect) by surveying nucleotide variation across a highly recombining approximately 88-kb genomic fragment in an African population of Drosophila simulans. We find a core region of up to 38 kb with a major haplotype at intermediate frequency. The extended haplotype structure that gradually vanishes until disappearing is unusual for a highly recombining region. Both the presence in the structured genomic domain of a single major haplotype depleted of variability and the detected spatial pattern of variation along the approximately 88-kb fragment are incompatible with neutral predictions in a panmictic population. A major role of demographic effects could also be discarded. The observed pattern of variation clearly provides evidence that directional selection has acted recently on this region, sweeping out variation around a strongly adaptive mutation. Our findings suggest a major role of positive selection in shaping DNA variability even in highly recombining regions.

Adaptation, Biological↗

PubMed2003

Patterns of nucleotide polymorphism and divergence in the odorant-binding protein genes OS-E and OS-F: analysis in the melanogaster species subgroup of Drosophila.

The Olfactory Specific-E and -F genes (OS-E and OS-F) belong to the odorant-binding protein gene family, which includes the general odorant-binding proteins and the pheromone-binding proteins. In Drosophila melanogaster, these genes are arranged in tandem in a genomic region near the centromere of chromosome arm 3R. We examined the pattern of DNA sequence variation in an approximately 7-kb genomic region encompassing the two OS genes in four species of the melanogaster subgroup of Drosophila and in a population sample of D. melanogaster. We found that both the OS-E and the OS-F gene are present in all surveyed species. Nucleotide divergence estimates would support that the two genes are functional, although they diverge in their functional constraint. The pattern of nucleotide variation in D. melanogaster also differed between genes. Variation in the OS-E gene region exhibited an unusual and distinctive pattern: (i) a relatively high number of fixed amino acid replacements in the encoded protein and (ii) a peak of nucleotide polymorphism around the OS-E gene. These results are unlikely under the neutral model and suggest the action of natural selection in the evolution of the two odorant-binding protein genes.

Amino Acid Sequence↗

PubMed2002

The nature of introns 4-7 largely reflects the lineage specificity of HLA-A alleles.

For most HLA-A alleles the phylogeny of the 3' non-coding regions has not yet been studied systematically. In this study, we have determined the sequences of introns 4-7 in 50 HLA-A variants, and have computed nucleotide substitution rates and phylogenetic relationships. The A2/A28, A9, and A10 groups were characterized by clear lineage specificity. For the A19 group, lineage specificity was weaker. A*3001 clustered together with the alleles of the A1/A3/A11/A36 serological family, but not with the A19 group alleles. Reduced lineage specificity was also observed for the alleles of the A1/A3/A11/A36groups. The 3' intron sequences of A*8001 were clearly distinct from all other alleles studied. In several cases two allelic groups shared identical intron sequences, whereby the patterns varied with the introns. A similar situation has been previously described for the 5' introns. Since recombination is the major mechanism of HLA diversification, the intronic lineage specificity corresponds to the comparatively lower recombination rate of the HLA-A 3' exons. The low level of recombination within the 3' region of HLA-A is supported by the low CpG content with a maximum of 3.0% in this region compared with up to 10.7% in the 5' region. Apart from phylogenetic studies of HLA diversity and diversification, the sequence data obtained in our study may prove valuable for the development of a haplotype-specific sequencing strategy for the HLA-A3' exons and for the explanation of recombination events in newly described HLA class I alleles.

Base Sequence↗

PubMed2002

Statistical properties of new neutrality tests against population growth.

A number of statistical tests for detecting population growth are described. We compared the statistical power of these tests with that of others available in the literature. The tests evaluated fall into three categories: those tests based on the distribution of the mutation frequencies, on the haplotype distribution, and on the mismatch distribution. We found that, for an extensive variety of cases, the most powerful tests for detecting population growth are Fu's F(S) test and the newly developed R(2) test. The behavior of the R(2) test is superior for small sample sizes, whereas F(S) is better for large sample sizes. We also show that some popular statistics based on the mismatch distribution are very conservative.

Computer Simulation↗