Patterns Of Sequence Polymorphism Research Articles

Evolutionary processes in populations of Cryptosporidium inferred from gp60 sequence data.

Cryptosporidiosis is one of the most common human infectious diseases globally. The gp60 gene has been adopted as a key marker for molecular epidemiological investigations into this protozoan disease because of the capability to characterize genotypes and detect variants within Cryptosporidium species infecting humans. However, we know relatively little about the potential spatial and temporal variation in population demography that can be inferred from this gene beyond that it is recognized to be under selective pressure. Here, we analyzed the genetic variation in time and space within two putative populations of Cryptosporidium in New Zealand to infer the processes behind the patterns of sequence polymorphism. Analyses using Tajima's D, Fu, and Li's D* and F* tests show significant departures from neutrality in some populations and indicate the selective maintenance of alleles within some populations. Demographic analyses showed distortions in the pattern of the genetic variability caused by high recombination rates and population expansion, which was observed in case notification data. Our results showed that processes acting on populations that have similar effects can be distinguished from one another and multiple processes can be detected acting at the same time. These results are significant for prediction of the parasite dynamics and potential mechanisms of long-term changes in the risk of cryptosporidiosis in humans.

Ontogenetic sequence reconstruction and sequence polymorphism in extinct taxa: an example using early tetrapods (Tetrapoda: Lepospondyli)

Ontogenetic sequence reconstruction is challenging particularly for extinct taxa because of when, where, and how fossils preserve. Different methods of reconstruction exist, but the effects of preservational bias, the applicability of size-independent methods, and the prevalence of sequence polymorphism (intraspecific variation) remain unexplored for paleontological data. Here I compare five different methods of ontogenetic sequence reconstruction and their effects on the detection of sequence polymorphism, using a large collection of the extinct vertebrates Microbrachis pelikani and Hyloplesion longicostatum. The postcranial ossification sequences presented here for those taxa are the first examples known for extinct lepospondyls. Sequences were reconstructed according to skull length, trunk length, increasing number of ontogenetic events, majority-rule consensus, and Ontogenetic Sequence Analysis (OSA). Results generally were in agreement, demonstrating that paleontological data may be used to robustly reconstruct developmental patterns. When reconstructing sequences based on fossils, size-based methods and OSA are more objective and less dependent on preservational bias than other techniques. Apart from the other methods, OSA also allows for statistical analysis of observed and predicted polymorphism. However, OSA requires a large sample size to yield meaningful results, and size-based methods are justified in paleontological studies when sample size is limited by poor preservation. Different methods of reconstruction detected different patterns of sequence polymorphism, although across all methods the magnitude of sequence variation for M. pelikani and H. longicostatum (1.3−3.4%) was within the lower range of values reported for extant vertebrates. Compared with other extinct and extant tetrapods, all sequence reconstruction methods consistently showed that M. pelikani and H. longicostatum exhibit advanced ossification of the pubis and delayed ossification of the scapula. However, the postcranial ossification sequences of these two taxa largely are congruent with those of other tetrapods, suggesting an underlying conservative ancestral pattern that evolved early in tetrapod history.

Patterns of sequence polymorphism in the fleshless berry locus in cultivated and wild Vitis vinifera accessions

BackgroundUnlike in tomato, little is known about the genetic and molecular control of fleshy fruit development of perennial fruit trees like grapevine (Vitis vinifera L.). Here we present the study of the sequence polymorphism in a 1 Mb grapevine genome region at the top of chromosome 18 carrying the fleshless berry mutation (flb) in order, first to identify SNP markers closely linked to the gene and second to search for possible signatures of domestication.ResultsIn total, 62 regions (17 SSR, 3 SNP, 1 CAPS and 41 re-sequenced gene fragments) were scanned for polymorphism along a 3.4 Mb interval (85,127-3,506,060 bp) at the top of the chromosome 18, in both V. vinifera cv. Chardonnay and a genotype carrying the flb mutation, V. vinifera cv. Ugni Blanc mutant. A nearly complete homozygosity in Ugni Blanc (wild and mutant forms) and an expected high level of heterozygosity in Chardonnay were revealed. Experiments using qPCR and BAC FISH confirmed the observed homozygosity. Under the assumption that flb could be one of the genes involved into the domestication syndrome of grapevine, we sequenced 69 gene fragments, spread over the flb region, representing 48,874 bp in a highly diverse set of cultivated and wild V. vinifera genotypes, to identify possible signatures of domestication in the cultivated V. vinifera compartment. We identified eight gene fragments presenting a significant deviation from neutrality of the Tajima's D parameter in the cultivated pool. One of these also showed higher nucleotide diversity in the wild compartments than in the cultivated compartments. In addition, SNPs significantly associated to berry weight variation were identified in the flb region.ConclusionsWe observed the occurrence of a large homozygous region in a non-repetitive region of the grapevine otherwise highly-heterozygous genome and propose a hypothesis for its formation. We demonstrated the feasibility to apply BAC FISH on the very small grapevine chromosomes and provided a specific probe for the identification of chromosome 18 on a cytogenetic map. We evidenced genes showing putative signatures of selection and SNPs significantly associated with berry weight variation in the flb region. In addition, we provided to the community 554 SNPs at the top of chromosome 18 for the development of a genotyping chip for future fine mapping of the flb gene in a F2 population when available.

Impact of mating systems on patterns of sequence polymorphism in flowering plants

A fundamental challenge in population genetics and molecular evolution is to understand the forces shaping the patterns of genetic diversity within and among species. Among them, mating systems are thought to have important influences on molecular diversity and genome evolution. Selfing is expected to reduce effective population size, Ne, and effective recombination rates, directly leading to reduced polymorphism and increased linkage disequilibrium compared with outcrossing. Increased isolation between populations also results directly from selfing or indirectly from evolutionary changes, such as small flowers and low pollen output, leading to greater differentiation of molecular markers than under outcrossing. The lower effective recombination rate increases the likelihood of hitch-hiking, further reducing within-deme diversity of selfers and thus increasing their genetic differentiation. There are also indirect effects on molecular evolutionary processes. Low Ne reduces the efficacy of selection; in selfers, selection should thus be less efficient in removing deleterious mutations. The rarity of heterozygous sites in selfers leads to infrequent action of biased conversion towards GC, which tends to increase sequences' GC content in the most highly recombining genome regions of outcrossers. To test these predictions in plants, we used a newly developed sequence polymorphism database to investigate the effects of mating system differences on sequence polymorphism and genome evolution in a wide set of plant species. We also took into account other life-history traits, including life form (whether annual or perennial herbs, and woody perennial) and the modes of pollination and seed dispersal, which are known to affect enzyme and DNA marker polymorphism. We show that among various life-history traits, mating systems have the greatest influence on patterns of polymorphism.

Sequence polymorphism in the Epstein--Barr virus latent membrane protein (LMP)-2 gene

Latent membrane protein 2A (LMP-2A) is expressed in Epstein-Barr virus transformed B lymphocytes in vitro and has been detected in various types of EBV-associated malignancies. LMP-2A interferes with membrane signal transduction through phosphorylation of its hydrophilic N-terminal domain and binding of the cellular tyrosine kinases encoded by fyn and lyn. In vitro, the domain can block calcium influx and participate in signal transduction inducing cytokine production. These two activities are differently affected by site-directed mutagenesis of potentially phosphorylated amino acid residues. Several potential tyrosine protein kinase recognition motifs have been identified including an antigen recognition motif (ARAM). ARAMs are activated by tyrosine phosphorylation that enables binding of tyrosine protein kinases such as lyn and fyn. To assess the importance of potential sequence variation in natural EBV infection and in tumourigenesis, the sequence of the LMP-2A N-terminal domain was determined in 28 EBV isolates, including 14 fresh tumour isolates. Comparison of the corresponding sequences with the prototype B95 strain indicates that LMP-2 is generally conserved with a few base pair changes resulting in conservative amino acid changes in an occasional isolate. However, five single-base loci were frequently mutated, resulting in three patterns of sequence polymorphism in exon 1 of LMP-2A. The patterns did not segregate with EBV Type 1 or Type 2 and were detected in both lymphoid and epithelial tissues. Four of the most frequent mutations at loci 166627, 166750, 166796 and 166805 (codons 23, 63, 79 and 82) could potentially affect tyrosine protein kinase binding motifs. The pivotal tyrosines (codons 74 and 85) and leucines (codons 77 and 88) of the LMP-2 ARAM were not affected in any of the isolates, suggesting that ARAM function is important for EBV infection in vivo. However, the inter-spacing positions 79 and 82 were distinct in more than 50% of the isolates. These prevalent polymorphisms could influence interaction of the LMP-2 cytoplasmic domain with specific cellular ligand proteins.