Dataset Information

The Impact of Natural Selection on Short Insertion and Deletion Variation in the Great Tit Genome.

ABSTRACT: Insertions and deletions (INDELs) remain understudied, despite being the most common form of genetic variation after single nucleotide polymorphisms. This stems partly from the challenge of correctly identifying the ancestral state of an INDEL and thus identifying it as an insertion or a deletion. Erroneously assigned ancestral states can skew the site frequency spectrum, leading to artificial signals of selection. Consequently, the selective pressures acting on INDELs are, at present, poorly resolved. To tackle this issue, we have recently published a maximum likelihood approach to estimate the mutation rate and the distribution of fitness effects for INDELs. Our approach estimates and controls for the rate of ancestral state misidentification, overcoming issues plaguing previous INDEL studies. Here, we apply the method to INDEL polymorphism data from ten high coverage (∼44×) European great tit (Parus major) genomes. We demonstrate that coding INDELs are under strong purifying selection with a small proportion making it into the population (∼4%). However, among fixed coding INDELs, 71% of insertions and 86% of deletions are fixed by positive selection. In noncoding regions, we estimate ∼80% of insertions and ∼52% of deletions are effectively neutral, the remainder show signatures of purifying selection. Additionally, we see evidence of linked selection reducing INDEL diversity below background levels, both in proximity to exons and in areas of low recombination.

SUBMITTER: Barton HJ

PROVIDER: S-EPMC6543879 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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The Impact of Natural Selection on Short Insertion and Deletion Variation in the Great Tit Genome.

Barton Henry J HJ Zeng Kai K

Genome biology and evolution 20190601 6

Insertions and deletions (INDELs) remain understudied, despite being the most common form of genetic variation after single nucleotide polymorphisms. This stems partly from the challenge of correctly identifying the ancestral state of an INDEL and thus identifying it as an insertion or a deletion. Erroneously assigned ancestral states can skew the site frequency spectrum, leading to artificial signals of selection. Consequently, the selective pressures acting on INDELs are, at present, poorly re ...[more]

PMID: 30924871

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Project description:BACKGROUND: One of the major issues concerning disease ecology and conservation is knowledge of the factors that influence the distribution of parasites and consequently disease outbreaks. This study aimed to investigate avian haemosporidian composition and the distribution of these parasites in three altitudinally separated great tit (Parus major) populations in western Switzerland over a three-year period. The objectives were to determine the lineage diversity of parasites occuring across the study populations and to investigate whether altitudinal gradients govern the distribution of haemosporidian parasites by lineage. METHODS: In this study molecular approaches (PCR and sequencing) were used to detect avian blood parasites (Plasmodium sp., Haemoproteus sp. and Leucocytozoon sp.) in populations of adult great tits caught on their nests during three consecutive breeding seasons. RESULTS: High levels of parasite prevalence (88-96%) were found across all of the study populations with no significant altitude effect. Altitude did, however, govern the distribution of parasites belonging to different genera, with Plasmodium parasites being more prevalent at lower altitudes, Leucocytozoon parasites more at high altitude and Haemoproteus parasite prevalence increasing with altitude. A total of 27 haemosporidian parasite lineages were recorded across all study sites, with diversity showing a positive correlation to altitude. Parasites belonging to lineage SGS1 (P. relictum) and PARUS4 and PARUS19 (Leucocytozoon sp.) dominated lower altitudes. SW2 (P. polare) was the second most prevalent lineage of parasite detected overall and these parasites were responsible for 68% of infections at intermediate altitude, but were only documented at this one study site. CONCLUSIONS: Avian haemosporidian parasites are not homogeneously distributed across host populations, but differ by altitude. This difference is most probably brought about by environmental factors influencing vector prevalence and distribution. The high occurrence of co-infection by different genera of parasites might have pronounced effects on host fitness and should consequently be investigated more rigorously.

Project description:Short insertions and deletions (indels) are the second most abundant form of human genetic variation, but our understanding of their origins and functional effects lags behind that of other types of variants. Using population-scale sequencing, we have identified a high-quality set of 1.6 million indels from 179 individuals representing three diverse human populations. We show that rates of indel mutagenesis are highly heterogeneous, with 43%-48% of indels occurring in 4.03% of the genome, whereas in the remaining 96% their prevalence is 16 times lower than SNPs. Polymerase slippage can explain upwards of three-fourths of all indels, with the remainder being mostly simple deletions in complex sequence. However, insertions do occur and are significantly associated with pseudo-palindromic sequence features compatible with the fork stalling and template switching (FoSTeS) mechanism more commonly associated with large structural variations. We introduce a quantitative model of polymerase slippage, which enables us to identify indel-hypermutagenic protein-coding genes, some of which are associated with recurrent mutations leading to disease. Accounting for mutational rate heterogeneity due to sequence context, we find that indels across functional sequence are generally subject to stronger purifying selection than SNPs. We find that indel length modulates selection strength, and that indels affecting multiple functionally constrained nucleotides undergo stronger purifying selection. We further find that indels are enriched in associations with gene expression and find evidence for a contribution of nonsense-mediated decay. Finally, we show that indels can be integrated in existing genome-wide association studies (GWAS); although we do not find direct evidence that potentially causal protein-coding indels are enriched with associations to known disease-associated SNPs, our findings suggest that the causal variant underlying some of these associations may be indels.

Project description:The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections.

Dataset Information

The Impact of Natural Selection on Short Insertion and Deletion Variation in the Great Tit Genome.

Publications

The Impact of Natural Selection on Short Insertion and Deletion Variation in the Great Tit Genome.

Similar Datasets

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