13 research outputs found
Phylogenomic Analysis Reveals Dynamic Evolutionary History of the Drosophila Heterochromatin Protein 1 (HP1) Gene Family
Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin
Recommended from our members
Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation
Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2–5.3) and IL-6 (OR; 95% CI: 2.6; 1.03–6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2–6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3–5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1–3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1–4.2)
Results of the population genetic analyses of HP1 genes that occur in <i>D. melanogaster</i>.
<p>ENC = effective number of codons, Syn = synonymous, Nonsyn = nonsynonymous, %ile = percentile, ave n = average # alleles, NS = nonsynonymous, S = synonymous, π ratio = NSπ/Sπ, poly = #polymorphisms, fix = # fixations, NI = neutrality index, FETpval = Fisher's Exact Test probability value.</p
Results from the molecular evolution analysis of genes that occur in <i>D. melanogaster</i>.
<p>The dN/dS refers to a <i>D. melanogaster-D. simulans</i> pairwise calculation.</p
PAML analysis results of genes that occur in <i>D. melanogaster</i>.
<p><i>mel</i> = <i>D. melanogaster</i>, <i>sim</i> = <i>D. simulans</i>, <i>sec</i> = <i>D. sechellia</i>, <i>yak</i> = <i>D. yakuba</i>, <i>ere</i> = <i>D. erecta</i>, <i>tak</i> = <i>D. takahashii</i>, <i>bia</i> = <i>D. biarmipes</i>, <i>ele</i> = <i>D. elegans</i>, <i>fic</i> = <i>D. ficusphilia</i>.</p
Delineating HP1E loss in the <i>obscura</i> group.
<p>We amplified the syntenic region of HP1E in the obscura group and successfully identified intact <i>HP1E</i> genes from <i>D. guanche</i> and <i>D. bifasciata</i>. We found highly pseudogenized versions of <i>HP1E</i> in <i>D. azteca</i>, <i>D. affinis</i> (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729.s003" target="_blank">Figure S3</a>). These latter four species also share dramatic karyotypic changes specific to this lineage including an <i>X:3L</i> fusion, a <i>Y:4</i> fusion and a neo-<i>Y</i> (indicated as <i>Y</i>′ in figure, note that <i>3L</i> and <i>4</i> = elements “D” and “F”, respectively). Thus, to the level of resolution possible from the available species, <i>HP1E</i> loss coincided with the karyotypic changes in the <i>obscura group</i>. The <i>HP1E</i> cytolocation on chromosome <i>3R</i> (element “E”), post-karyotype evolution, is apparently undisrupted.</p
HP1 diversity in Drosophila genomes.
<p>A. Phylogeny of 12 Drosophila species, which were each queried for HP1-like genes in this study <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729-Clark1" target="_blank">[2]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729-Adams1" target="_blank">[42]</a>. Scale bar refers to the approximate divergence time between these species <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729-Clark1" target="_blank">[2]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729-Adams1" target="_blank">[42]</a>. B. Schematics of proteins encoded by the various HP1 genes in Drosophila genomes are presented alongside the HP1 gene name. Highlighted in boxes are the canonical chromo (green) and shadow (blue) domains that typify HP1 genes. Note that in some instances, we were unable to confirm the exact gene model and therefore the lengths of the N-terminal tails (these are indicated with dashed lines). We also report the <i>D. melanogaster</i> cytolocation of the gene or if the gene is absent in <i>D. melanogaster</i>, the sytenic location in the <i>D. melanogaster</i> genome based on neighboring genes. The final column reports the species in which the gene is found. Genes shaded gray represent founding HP1 gene family members that were reported in the original <i>D. melanogaster</i> genome sequencing study <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729-Adams1" target="_blank">[42]</a>. “*” refers to an allele that harbors a premature stop codon but conserved C-terminal sequence (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729.s007" target="_blank">Table S1</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729.s004" target="_blank">Figure S4</a>) and predicted CD and CSD domains, consistent with a polymorphic full length gene or an incorrect base call.</p
Phylogenetic relationships among the Drosophila HP1 genes.
<p>We constructed phylogenetic trees generated in BEAST (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#s4" target="_blank">Materials and Methods</a>) using codon-based alignments of the Chromodomain (A) or Chromoshadow domain (B) based on a log-normal relaxed molecular clock <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729-Drummond2" target="_blank">[58]</a>. For clarity, we only present posterior probabilities for major clade relationships rather than between orthologs of the same gene (complete trees with all posterior probability support values indicated can be found in supplemental data (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002729#pgen.1002729.s005" target="_blank">Figure S5A, S5B</a>)). In most instances orthologs grouped together with a high degree of support (exceptions, including the <i>HP1Lcsd</i> genes are discussed in the main text). Genes that are shaded gray refer to partial HP1s that encode either a chromodomain (in A) or shadow domains (in B) only. Scale bar refers to the expected number of substitutions per site.</p
Expression patterns of Drosophila HP1 genes.
<p>RT-PCR analysis on several adult tissues from male and female Drosophila from each of 5 species. RP49 represents a control locus. “UMB:” <i>umbrea</i>, “OXP”: <i>oxpecker</i>, “-”: no DNA/RNA control; “g”: genomic DNA, “M”: whole male, “F”: whole female; “H”:head; “T”: testis, “C”: carcass (gonadectomized, headless individuals); “O” ovaries. Gray lines refer to the absence of the gene in the particular species. We present the analyses for full-length HP1 genes in (A), for partial CD-only HP1s in (B) and for partial CSD-only HP1s in (C).</p