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Department of Evolution, Genomics and Systematics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden. websterm@tcd.ie Interspersed repeats have emerged as a valuable tool for studying neutral patterns of molecular evolution. Here we analyze variation in the rate and pattern of nucleotide substitution across all autosomes in the chicken genome by comparing the present-day CR1 repeat sequences with their ancestral copies and reconstructing nucleotide substitutions with a maximum likelihood model. The results shed light on the origin and evolution of large-scale heterogeneity in GC content found in the genomes of birds and mammals--the isochore structure. In contrast to mammals, where GC content is becoming homogenized, heterogeneity in GC content is being reinforced in the chicken genome. This is also supported by patterns of substitution inferred from alignments of introns in chicken, turkey, and quail. Analysis of individual substitution frequencies is consistent with the biased gene conversion (BGC) model of isochore evolution, and it is likely that patterns of evolution in the chicken genome closely resemble those in the ancestral amniote genome, when it is inferred that isochores originated. Microchromosomes and distal regions of macrochromosomes are found to have elevated substitution rates and a more GC-biased pattern of nucleotide substitution. This can largely be accounted for by a strong correlation between GC content and the rate and pattern of substitution. The results suggest that an interaction between increased mutability at CpG motifs and fixation biases due to BGC could explain increased levels of divergence in GC-rich regions.

Regional biases in substitution pattern are likely to be responsible for the large-scale variation in base composition observed in vertebrate genomes. However, the evolutionary forces responsible for these biases are still not clearly defined. In order to study the processes of mutation and fixation across the entire human genome, we analyzed patterns of substitution in Alu repeats since their insertion. We also studied patterns of human polymorphism within the repeats. There is a highly significant effect of recombination rate on the pattern of substitution, whereas no such effect is seen on the pattern of polymorphism. These results suggest that regional biases in substitution are caused by biased gene conversion, a process that increases the probability of fixation of mutations that increase GC content. Furthermore, the strongest correlate of substitution patterns is found to be male recombination rates rather than female or sex-averaged recombination rates. This indicates that in addition to sexual dimorphism in recombination rates, the sexes also differ in the relative rates of crossover and gene conversion., Fullt text article at mbe.oupjournals.org

Alu elements are not distributed homogeneously throughout the human genome: old elements are preferentially found in the GC-rich parts of the genome, while young Alus are more often found in the GC-poor parts of the genome. The process giving rise to this differential distribution remains poorly understood. Here we investigate whether this pattern could be due to a preferential degradation of Alu elements integrated in GC-poor regions by small indel mutations. We aligned 5.1 Mb of human and chimpanzee sequences and examined whether the rate of insertion and deletion inside Alu elements differed according to the base composition surrounding them. We found that Alu elements are not preferentially degraded in GC-poor regions by indel events. We also looked at whether very young L1 elements show the same change in distribution compared to older ones. This analysis indicated that L1 elements also show a shift in their distribution, although we could not assess it as precisely as for Alu elements. We propose that the differential distribution of Alu elements is likely to be due to a change in their pattern of insertion or their probability of fixation through evolutionary time.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder commonly caused by large expansions of a GAA repeat in the first intron of the frataxin gene, FRDA. The expansion of the triplet repeat is localized within an Alu sequence. FRDA GAA-repeat alleles can be divided into three classes depending on their lengths: short normal alleles (SN), long normal alleles (LN) and expanded pathological alleles (E). We made an accurate analysis of the Alu sequence containing the GAA repeat. We found a new single-nucleotide polymorphism (SNP) that is the closest one to the GAA repeat. We studied this new SNP and the polymorphic polyA region contiguous to the GAA triplets in two populations with different frequencies of FRDA. We found that, while both E and LN alleles seem to be genetically homogeneous and likely related, SN represents a more heterogeneous class of alleles. Indeed, one SNP variation (T) was more frequently associated with (GAA)(8) alleles, whereas the other one (C) with (GAA)(9) repeat(s). The long normal and expanded alleles presented the C haplotype. The same correlation was described for polyA-tract polymorphisms. Thus, 14A was commonly associated with (GAA)(8) alleles and 17A with (GAA)(9) alleles. The long normal alleles more frequently showed the 17A haplotype. Our data seem to suggest that all the E alleles come from LN alleles, while LN alleles come from a defined subclass of SN alleles., Comparative Study, Journal Article, info:eu-repo/semantics/published