Recurrent invasion and extinction of a selfish gene

Abstract

Homing endonuclease genes show super-Mendelian inheritance, which allows them to spread in populations even when they are of no benefit to the host organism. To test the idea that regular horizontal transmission is necessary for the long-term persistence of these genes, we surveyed 20 species of yeasts for the omega-homing endonuclease gene and associated group I intron. The status of omega could be categorized into three states (functional, nonfunctional, or absent), and status was not clustered on the host phylogeny. Moreover, the phylogeny of omega differed significantly from that of the host, strong evidence of horizontal transmission. Further analyses indicate that horizontal transmission is more common than transposition, and that it occurs preferentially between closely related species. Parsimony analysis and coalescent theory suggest that there have been 15 horizontal transmission events in the ancestry of our yeast species, through simulations indicate that this value is probably an underestimate. Overall, the data support a cyclical model of invasion, degeneration, and loss, followed by reinvasion, and each of these transitions is estimated to occur about once every 2 million years. The data are thus consistent with the idea that frequent horizontal transmission is necessary for the long-term persistence of homing endonuclease genes, and further, that this requirement limits these genes to organisms with easily accessible germ lines. The data also show that mitochondrial DNA sequences are transferred intact between yeast species; if other genes do not show such high levels of horizontal transmission, it would be due to lack of selection, rather than lack of opportunity.

Figure 1

(A) Structure of ω. White boxes represent the mitochondrial LSU rDNA, black boxes represent the ω group I intron, and the stippled box represents the ω HEG. The two boxes with horizontal lines represent the endonuclease recognition site, which is interrupted by the presence of ω. Also shown are the PCR primer-binding sites (not to scale). (B) Consensus primary and secondary structure of the group I introns, showing base-paired regions P1 to P9.3. If present, HEGs are found in region P8. Solid black lines represent areas of secondary structure that are present in all introns, but are not sequentially conserved. Dashed arrows connect nucleotides that have been separated for ease of display. Stem-loop structures in gray are optional or unalignable (P6b is found only in Kluyveromyces dobzhanskii, K. lactis, Zygosaccharomyces bisporus and Zygosaccharomyces rouxii; P9.2 is found only in Saccharomyces castellii and S. sp-Japan) and were not included in the phylogenetic analysis. Areas A–H, indicated by thick gray lines, are homologous areas that were aligned independently and used in phylogenetic analysis. Exon sequences are in lowercase letters.

Figure 2

Intron status and phylogenetic relationships of yeasts. Bootstrap consensus tree (1,000 replicates) obtained from a maximum parsimony branch-and-bound analysis of 18S + 5.8S data, with gaps scored as fifth bases. The bootstrap score for each branch is shown. Likelihood analyses gave the same topology. The root is inferred from a larger analysis of 18S rDNA of hemiascomycete yeasts (ref. and unpublished observations). (Inset) A separate analysis of the Saccharomyces sensu stricto, using complete internal transcribed spacer sequence data and a parsimony branch-and-bound bootstrap analysis (1,000 replicates). Numbers in parentheses identify the Centraalbureau Voor Schimmelcultures cultures; the genus “T.” is Torulaspora. t indicates the type strain.

Figure 3

Phylogenetic comparisons between intron, HEG, and host. The histogram associated with each tanglegram shows the distribution of summed tree lengths for random partitions of the data; arrows show the length of the actual partition.

Figure 4

Cyclical model of ω gain and loss. Numbers in brackets indicate the number of taxa, of the 20 surveyed, with that intron state; numbers in parentheses are maximum likelihood average waiting times for changing from one state to the next (millions of years), calculated by mapping the character states onto the following most parsimonious tree, with branch lengths estimated by maximum likelihood, forcing a molecular clock: (((((((((Brazil: 0.00007, S. paradoxus: 0.00007): 0.00034, S. cerevisiae: 0.00041): 0.00042, Japan: 0.00083): 0.00015, (S. bayanus: 0.00009, S. pastorianus: 0.00009): 0.00089): 0.010178, (S. unisporus: 0.009518, S. exiguus: 0.009518): 0.001636): 0.000697, (S. dairensis: 0.004508, S. castellii: 0.004508): 0.007343): 0.001739, ((((T. pretoriensis: 0.000591, T. delbrueckii: 0.000591): 0.001229, T. globosa: 0.001820): 0.009593, (Z. rouxii: 0.007138, (Z. bailii: 0.003529, Z. bisporus: 0.003529): 0.003609): 0.004275): 0.001462, K. polysporus: 0.012875): 0.000716): 0.004425, K. thermotolerans: 0.018016): 0.009386, (K. dobzhanskii: 0.002081, K. lactis: 0.002081): 0.025320): 0.000000.