Diverse transposable element landscapes in pathogenic and nonpathogenic yeast models: the value of a comparative perspective

Abstract

Genomics and other large-scale analyses have drawn increasing attention to the potential impacts of transposable elements (TEs) on their host genomes. However, it remains challenging to transition from identifying potential roles to clearly demonstrating the level of impact TEs have on genome evolution and possible functions that they contribute to their host organisms. I summarize TE content and distribution in four well-characterized yeast model systems in this review: the pathogens Candida albicans and Cryptococcus neoformans, and the nonpathogenic species Saccharomyces cerevisiae and Schizosaccharomyces pombe. I compare and contrast their TE landscapes to their lifecycles, genomic features, as well as the presence and nature of RNA interference pathways in each species to highlight the valuable diversity represented by these models for functional studies of TEs. I then review the regulation and impacts of the Ty1 and Ty3 retrotransposons from Saccharomyces cerevisiae and Tf1 and Tf2 retrotransposons from Schizosaccharomyces pombe to emphasize parallels and distinctions between these well-studied elements. I propose that further characterization of TEs in the pathogenic yeasts would enable this set of four yeast species to become an excellent set of models for comparative functional studies to address outstanding questions about TE-host relationships.

Keywords: Candida albicans; Cryptococcus neoformans; Retrotransposon; Saccharomyces cerevisiae; Schizosaccharomyces pombe; Tf1; Tf2; Transposable element; Ty1; Ty3.

Fig. 1

Comparison of transposition cycles of four subclasses of transposable elements (TEs). Simplified representations of major steps in the transposition cycles of two subclasses of DNA transposons (cut-and-paste and peel-and-paste) and two subclasses of retrotransposons (long terminal repeat (LTR) and non-LTR) are shown. Light gray and lavender lines represent donor and target genomic sites, respectively. Boxed arrowheads indicate terminal inverted repeats (cut-and-paste) or LTRs. Curved black arrows indicate repair of the donor site after transposon excision, small purple or blue arrows represent new DNA synthesis, and wavy lines represent RNA. TP- transposase (DDE-type for cut-and-paste or HUH nuclease/helicase-type for peel-and-paste), RT- reverse transcriptase, IN- integrase, EN- endonuclease domain.

Fig. 2

Distributions of TEs in four model yeasts. Gray lines and filled boxes are schematic representations of major DNA sequence features present on chromosomes without any intention of indicating relative size, position, or presence of specific sequences on the same chromosome. Sequence features include: pA- poly(A) sites; CEN- centromeres; HML/R or mat2/3- hidden/silent mating loci; MAT, mat1, or MTL- mating locus; Pol2 or Pol3- RNA Polymerase II or III-transcribed genes; rDNA- ribosomal DNA; TEL- telomeres; ? - unknown/no bias for sequence features. Vertical arrows indicate sites of TE insertions and the relative proportions of total insertions as shown in the key. Names above arrows indicate specific TEs or groups of TEs: DNA- DNA transposons, DNA/RT- DNA transposons or retrotransposons, LTR- LTR retrotransposons or solo LTRs. Blue horizontal arrows indicate the direction of gene transcription.

Fig. 3

Structure and replication of retrotransposons. a Schematic representations of long terminal repeat (LTR) and non-LTR retrotransposons not drawn to scale. Blue boxes with white arrowheads indicate LTRs, and U3-R-U5 indicate regions of LTRs. EN- endonuclease, IN- integrase, pA- poly(A) sequence, PR- protease, RT- reverse transcriptase, RT-RH- reverse transcriptase/RNase H, UTR- untranslated region. b Graphic representation of major steps of retrotransposition through target-primed reverse transcription for non-LTR retrotransposons. c Graphic representation of major steps of retrotransposition for LTR retrotransposons. Colors of ellipses correspond to proteins from panel a, wavy lines represent RNA, boxed arrowheads represent LTRs, and thin blue arrows represent DNA strands newly synthesized by reverse transcriptase.

Fig. 4

Majors steps of reverse transcription for LTR retrotransposons. The gray box represents retrotransposon RNA with major sequence features not drawn to scale: LTR sequences U3, R, and U5; gag and pol ORFs; PBS- primer binding site; PPT- polypurine tract. The lavender shape indicates the tRNA primer, dashed blue arrows indicate newly synthesized DNA, and solid blue lines indicate DNA synthesized in a previous step.

Fig. 5

Characterized retrotransposons from three yeast species. Schematic representations of the indicated retrotransposon families drawn to scale. Boxed arrowheads indicate LTRs. Domains of proteins: EN- endonuclease, IN- integrase, PR- protease, RT- reverse transcriptase, RT-RH- reverse transcriptase-RNase H, ZF- zinc finger. pA- poly(A) sequence. The gag ORF of Ty1-Ty4 is raised relative to pol to indicate a + 1 translational frameshift between gag and pol. A vertical line with “stop” indicates the site of one or more stop codons.