Biomedical subjects

Carolina Bartolomé

Publications and source records attributed to Carolina Bartolomé.

12 recordsLinked to original sources

PubMed2006

Evolution of amino-acid sequences and codon usage on the Drosophila miranda neo-sex chromosomes.

We have studied patterns of DNA sequence variation and evolution for 22 genes located on the neo-X and neo-Y chromosomes of Drosophila miranda. As found previously, nucleotide site diversity is greatly reduced on the neo-Y chromosome, with a severely distorted frequency spectrum. There is also an accelerated rate of amino-acid sequence evolution on the neo-Y chromosome. Comparisons of nonsynonymous and silent variation and divergence suggest that amino-acid sequences on the neo-X chromosome are subject to purifying selection, whereas this is much weaker on the neo-Y. The same applies to synonymous variants affecting codon usage. There is also an indication of a recent relaxation of selection on synonymous mutations for genes on other chromosomes. Genes that are weakly expressed on the neo-Y chromosome appear to have a faster rate of accumulation of both nonsynonymous and unpreferred synonymous mutations than genes with high levels of expression, although the rate of accumulation when both types of mutation are pooled is higher for the neo-Y chromosome than for the neo-X chromosome even for highly expressed genes.

Amino Acid Sequence↗

PubMed2006

Rates and patterns of chromosomal evolution in Drosophila pseudoobscura and D. miranda.

Comparisons of gene orders between species permit estimation of the rate of chromosomal evolution since their divergence from a common ancestor. We have compared gene orders on three chromosomes of Drosophila pseudoobscura with its close relative, D. miranda, and the distant outgroup species, D. melanogaster, by using the public genome sequences of D. pseudoobscura and D. melanogaster and approximately 50 in situ hybridizations of gene probes in D. miranda. We find no evidence for extensive transfer of genes among chromosomes in D. miranda. The rates of chromosomal rearrangements between D. miranda and D. pseudoobscura are far higher than those found before in Drosophila and approach those for nematodes, the fastest rates among higher eukaryotes. In addition, we find that the D. pseudoobscura chromosome with the highest level of inversion polymorphism (Muller's element C) does not show an unusually fast rate of evolution with respect to chromosome structure, suggesting that this classic case of inversion polymorphism reflects selection rather than mutational processes. On the basis of our results, we propose possible ancestral arrangements for the D. pseudoobscura C chromosome, which are different from those in the current literature. We also describe a new method for correcting for rearrangements that are not detected with a limited set of markers.

Animals↗

PubMed2005

Estimating selection on nonsynonymous mutations.

The distribution of mutational effects on fitness is of fundamental importance for many aspects of evolution. We develop two methods for characterizing the fitness effects of deleterious, nonsynonymous mutations, using polymorphism data from two related species. These methods also provide estimates of the proportion of amino acid substitutions that are selectively favorable, when combined with data on between-species sequence divergence. The methods are applicable to species with different effective population sizes, but that share the same distribution of mutational effects. The first, simpler, method assumes that diversity for all nonneutral mutations is given by the value under mutation-selection balance, while the second method allows for stronger effects of genetic drift and yields estimates of the parameters of the probability distribution of mutational effects. We apply these methods to data on populations of Drosophila miranda and D. pseudoobscura and find evidence for the presence of deleterious nonsynonymous mutations, mostly with small heterozygous selection coefficients (a mean of the order of 10(-5) for segregating variants). A leptokurtic gamma distribution of mutational effects with a shape parameter between 0.1 and 1 can explain observed diversities, in the absence of a separate class of completely neutral nonsynonymous mutations. We also describe a simple approximate method for estimating the harmonic mean selection coefficient from diversity data on a single species.

Animals↗

PubMed2005

The detection of shared and ancestral polymorphisms.

There is increasing evidence that closely related species contain many polymorphisms that were present in their common ancestral species. Use of a more distant relative as an outgroup increases the ability to detect such ancestral polymorphisms. We describe a method for further improving estimates of the fraction of polymorphisms that are ancestral, and illustrate this with reference to data on Drosophila pseudoobscura and D. miranda. We also derive formulae for the proportion of fixations arising from ancestral polymorphisms and new mutations, respectively. The results should be useful for tests of selection based on the levels of expected and observed ancestral polymorphisms.

Alleles↗

PubMed2004

Patterns of selection on synonymous and nonsynonymous variants in Drosophila miranda.

We have investigated patterns of within-species polymorphism and between-species divergence for synonymous and nonsynonymous variants at a set of autosomal and X-linked loci of Drosophila miranda. D. pseudoobscura and D. affinis were used for the between-species comparisons. The results suggest the action of purifying selection on nonsynonymous, polymorphic variants. Among synonymous polymorphisms, there is a significant excess of synonymous mutations from preferred to unpreferred codons and of GC to AT mutations. There was no excess of GC to AT mutations among polymorphisms at noncoding sites. This suggests that selection is acting to maintain the use of preferred codons. Indirect evidence suggests that biased gene conversion in favor of GC base pairs may also be operating. The joint intensity of selection and biased gene conversion, in terms of the product of effective population size and the sum of the selection and conversion coefficients, was estimated to be approximately 0.65.

Animals↗

PubMed2004

The lack of recombination drives the fixation of transposable elements on the fourth chromosome of Drosophila melanogaster.

In regions of suppressed recombination, where selection is expected to be less efficient in removing slightly deleterious mutations, transposable element (TE) insertions should be more likely to drift to higher frequencies, and even to reach fixation. In the absence of excision events, once a TE is fixed it cannot be eliminated from the population, and accumulation of elements thus should become an irreversible process. In the long term, this can drive the degeneration of large non-recombining fractions of the genomes. Chromosome 4 of Drosophila melanogaster has very low levels of recombination, if any, and this could be causing its degeneration. Here we report the results of a PCR-based analysis of the population frequencies of TE insertions in a sample from three African natural populations. We investigated 27 insertions from 12 TE families, located in regions of either suppressed or free recombination. Our results suggest that TE insertions tend to be fixed in the non-recombining regions, particularly on the fourth chromosome. We have also found that this involves all types of elements, and that fixed insertions are significantly shorter and more divergent from the canonical sequence than those segregating in the sample (28.1% vs 86.3% of the canonical length, and average nucleotide divergence (D(XY)) = 0.082 vs 0.008, respectively). Finally, DNA-based elements seem to show a greater tendency to reach fixation than retrotransposons. Implications of these findings for the population dynamics of TEs, and the evolutionary forces that shape the patterns of genetic variation in regions of reduced recombination, are discussed.

Animals↗

PubMed2004

Estimates of the genomic mutation rate for detrimental alleles in Drosophila melanogaster.

The net rate of mutation to deleterious but nonlethal alleles and the sizes of effects of these mutations are of great significance for many evolutionary questions. Here we describe three replicate experiments in which mutations have been accumulated on chromosome 3 of Drosophila melanogaster by means of single-male backcrosses of heterozygotes for a wild-type third chromosome. Egg-to-adult viability was assayed for nonlethal homozygous chromosomes. The rates of decline in mean and increase in variance (DM and DV, respectively) were estimated. Scaled up to the diploid whole genome, the mean DM for homozygous detrimental mutations over the three experiments was between 0.8 and 1.8%. The corresponding DV estimate was approximately 0.11%. Overall, the results suggest a lower bound estimate of at least 12% for the diploid per genome mutation rate for detrimentals. The upper bound estimates for the mean selection coefficient were between 2 and 10%, depending on the method used. Mutations with selection coefficients of at least a few percent must be the major contributors to the effects detected here and are likely to be caused mostly by transposable element insertions or indels.

Alleles↗

PubMed2003

Haplotype structure of the stigmatic self-incompatibility gene in natural populations of Arabidopsis lyrata.

We describe analyses of almost full-length sequences (including both the kinase domain and the S-domain) of the putative SRK incompatibility gene of the self-incompatible plant Arabidopsis lyrata. In A. lyrata, the SRK S-domain controls the pistil recognition specificity, as in self-incompatible Brassica species. In alleles from plants derived from natural A. lyrata populations, nonsynonymous and synonymous site diversity values are very high in both domains; even in exons 3 to 7 of the kinase domain, which probably have no recognition functions, 39% of the amino acids are polymorphic. Within populations, diversity between alleles is high, as expected for an incompatibility locus, which should be under frequency-dependent selection within populations, whereas within the different putative allelic classes polymorphism is very low, as predicted from theoretical models when recombination is rare. Nonsynonymous site variability declines in the kinase domain with increasing distance from the S-domain border, although synonymous diversity remains high, and the introns are unalignable. A decline in nonsynonymous diversity is expected due to selective constraints in the kinase domain, in combination with recombination (allowing diversity to decrease at sites distant from those under balancing selection). However, it is unclear whether recombination occurs in the SRK locus, and interpretation of the observed diversity pattern is complicated by apparent gene conversion with a paralogous gene (or genes). Patterns of linkage disequilibrium in our SRK sequences do not support the conclusion that recombination occurs, which was suggested from previous analyses based on Brassica SLG sequences.

Alleles↗

PubMed2003

Inferences on the evolutionary history of the S-element family of Drosophila melanogaster.

The S-element family of transposable elements has been characterized in D. melanogaster. Attempts to find it in other Drosophila-related species have failed, suggesting that this element family may have recently invaded the D. melanogaster genome by horizontal transfer. In order to investigate its evolutionary history, we analyzed the patterns of DNA polymorphism among the S-element copies present in a sample genome (Drosophila Genome Project). The observed levels of nucleotide diversity are significantly lower than theoretical expectations based on the neutral model. This is consistent with evidence for ongoing gene conversion among copies and for purifying selection on the elements' sequences, particularly on the terminal inverted repeats. A phylogenetic analysis revealed that the members of the S-element family can be grouped into at least two genetically differentiated clusters. The level of divergence between these clusters suggests that the S elements invaded the genome of the ancestor of D. melanogaster before the speciation of the D. melanogaster complex. However, other relevant scenarios are also discussed.

Amino Acid Sequence↗

PubMed2003

Diversity and linkage of genes in the self-incompatibility gene family in Arabidopsis lyrata.

We report studies of seven members of the S-domain gene family in Arabidopsis lyrata, a member of the Brassicaceae that has a sporophytic self-incompatibility (SI) system. Orthologs for five loci are identifiable in the self-compatible relative A. thaliana. Like the Brassica stigmatic incompatibility protein locus (SRK), some of these genes have kinase domains. We show that several of these genes are unlinked to the putative A. lyrata SRK, Aly13. These genes have much lower nonsynonymous and synonymous polymorphism than Aly13 in the S-domains within natural populations, and differentiation between populations is higher, consistent with balancing selection at the Aly13 locus. One gene (Aly8) is linked to Aly13 and has high diversity. No departures from neutrality were detected for any of the loci. Comparing different loci within A. lyrata, sites corresponding to hypervariable regions in the Brassica S-loci (SLG and SRK) and in comparable regions of Aly13 have greater replacement site divergence than the rest of the S-domain. This suggests that the high polymorphism in these regions of incompatibility loci is due to balancing selection acting on sites within or near these regions, combined with low selective constraints.

Alleles↗

PubMed2002

S-element insertions are associated with the evolution of the Hsp70 genes in Drosophila melanogaster.

The "selfish DNA" theory postulates that transposable elements (TEs) are intragenomic parasites, and that natural selection against deleterious effects associated with their presence is the main force preventing their genomic spread in natural populations. In agreement with this model, TEs in Drosophila melanogaster populations are usually found at low frequencies in most genomic locations. Only a few cases of fixation of TE insertions have been reported, usually in regions of low recombination, where selection is expected to be less effective. Here, we report a population genetics study on the apparent fixation of an S-element in a highly recombining region in two natural populations of D. melanogaster. Three similar fragments of an S-element are inserted into the 5' regions of three members of a heat shock gene family, Hsp70 (Hsp70Aa and Hsp70Ab in polytene chromosome band 87A, and Hsp70Bb in 87C). A PCR-based analysis suggests that the insertions are fixed or at high frequencies in the entire species. A population survey of the levels of nucleotide sequence variation at the insertion site in 87C in two natural populations of D. melanogaster provided evidence for reduced levels of variation in the region, normal levels of recombination, and selection, reflected in a significant departure from neutrality of the variant frequency spectrum. This was particularly strong for the S-element inverted repeats (IRs) and suggests that these are of functional significance for the host.

Animals↗

PubMed2002

On the abundance and distribution of transposable elements in the genome of Drosophila melanogaster.

The abundance and distribution of transposable elements (TEs) in a representative part of the euchromatic genome of Drosophila melanogaster were studied by analyzing the sizes and locations of TEs of all known families in the genomic sequences of chromosomes 2R, X, and 4. TEs contribute to up to 2% of the sequenced DNA, which corresponds roughly to the euchromatin of these chromosomes. This estimate is lower than that previously available from in situ data and suggests that TEs accumulate in the heterochromatin more intensively than was previously thought. We have also found that TEs are not distributed at random in the chromosomes and that their abundance is more strongly associated with local recombination rates, rather than with gene density. The results are compatible with the ectopic exchange model, which proposes that selection against deleterious effects of chromosomal rearrangements is a major force opposing element spread in the genome of this species. Selection against insertional mutations also influences the observed patterns, such as an absence of insertions in coding regions. The results of the analyses are discussed in the light of recent findings on the distribution of TEs in other species.

Animals↗