A strong deletion bias in nonallelic gene conversion

Abstract

Gene conversion is the unidirectional transfer of genetic information between orthologous (allelic) or paralogous (nonallelic) genomic segments. Though a number of studies have examined nucleotide replacements, little is known about length difference mutations produced by gene conversion. Here, we investigate insertions and deletions produced by nonallelic gene conversion in 338 Drosophila and 10,149 primate paralogs. Using a direct phylogenetic approach, we identify 179 insertions and 614 deletions in Drosophila paralogs, and 132 insertions and 455 deletions in primate paralogs. Thus, nonallelic gene conversion is strongly deletion-biased in both lineages, with almost 3.5 times as many conversion-induced deletions as insertions. In primates, the deletion bias is considerably stronger for long indels and, in both lineages, the per-site rate of gene conversion is orders of magnitudes higher than that of ordinary mutation. Due to this high rate, deletion-biased nonallelic gene conversion plays a key role in genome size evolution, leading to the cooperative shrinkage and eventual disappearance of selectively neutral paralogs.

Figure 1. A phylogenetic approach for detecting insertions and deletions produced by nonallelic gene conversion.

Depicted is a hypothetical multiple alignment for pairs of paralogs in two sisters and an outgroup. The two sequences for each species represent a pair of paralogs, and the position of interest is colored in red. At this position, a length difference (A/−) exists between the paralogs in sister 2 and the outgroup (ancestral state). In the lineage of sister 1, an insertion (a) or deletion (b) of a nucleotide occurs in one paralog. Because these events result in the paralogs having matching states (A/A or −/−), they are consistent with gene conversion.

Figure 2. Properties of paralogs.

(a) Distribution of paralog sequence lengths in Drosophila (left) and primates (right). (b) Distribution of distances between pairs of paralogs located on the same chromosome in Drosophila (left) and primates (right). Distances are plotted on a log scale.

Figure 3. Indels consistent with gene conversion.

(a) Length distributions of all indels, insertions, and deletions in Drosophila (top) and primates (bottom). (b) Strength of deletion bias as a function of indel length in Drosophila (top) and primates (bottom). Error bars represent confidence limits from binomial sign tests (see Methods).

Figure 4. A phylogenetic approach for detecting fixed indels.

Depicted are hypothetical multiple alignments for pairs of paralogs in two sisters and an outgroup. The two sequences for each species represent a pair of paralogs, and the position of interest is colored in red. (a and b) At this position, both paralogs have identical lengths in sister 2 and the outgroup (ancestral state). In the lineage of sister 1, identical insertions (a) or deletions (b) occur in the paralogs. Each of these situations corresponds to an ordinary mutation producing an indel in one paralog, and this indel subsequently being transferred to the other paralog, or fixed, by gene conversion.