Long-drawn-out story

The referee suggested that we “… better define and explain ‘alternate segregation’ and ‘adjacent-1 segregation’. A simple figure illustrating these alternatives would help a great deal”. Back in 1964, La Chance, Riemann, and Hopkins (Genetics 49 959–972) wearied that ‘… chromosome pairing … in a translocation heterozygote … (has) been diagrammed and discussed in many publications …’. Geneticists working with translocations must continue to bear the cross of making ‘alt / adj-1’ figures afresh.

La Chance et al. reported an autosomal dominant mutant strain of the screw-worm fly Cochliomyia hominivorax. Females lay eggs in the wounds of warm-blooded animals, the maggots hatch and burrow through a feast of warm flesh, producing foul-smelling pus that attracts more flies. Mature larvae drop from the wound, pupate in the soil, bluish-green adults eclose, mate, and repeat nature’s ‘red in ovipositor and mouth-hook’ cycle. In mutant flies, a wing segment called the R-cell was blackened by pigmentation. The Brc (black R-cell) mutant phenotype was associated with a reciprocal translocation. Several generations of Brc × Brc crosses failed to establish a pure-breeding strain, suggesting that translocation-homozygotes were inviable. Remarkably, in each generation the ratio of Brc to wild-type flies was 3:1 instead of the expected 2:1 (1 lethal Brc/Brc : 2 Brc/ + heterozygotes : 1 +/+ wild-type homozygote). They proposed that in Brc males alternate segregation is twice as frequent as adjacent-1, a kind of chromosomal meiotic drive.

Segregation Distorter (SD) of Drosophila melanogaster is the best-studied meiotic drive (Genetics 192 33–53, 2012). All sperm from SD/SD ⁺ males pass on the SD-bearing chromosome-2 to their progeny. The Sd gene, in chromosome-2L, is a 3' truncated version of the Ran GTPase activating protein (RanGAP) gene created by a tandem duplication of a segment of the RanGAP gene. The C-terminally truncated Sd-RanGAP protein is enzymatically active but lacks the wild-type RanGAP’s localization signals. While wild-type RanGAP is tethered to the cytoplasmic side of the nuclear envelope, Sd-RanGAP accumulates in the nucleus and the cytoplasm. Mislocalization of Sd-RanGAP depletes nuclear RanGTP and impairs nuclear transport. SD chromosomes are Sd Rsp ⁱ in genotype, whereas most SD ⁺ chromosomes are Sd ⁺ Rsp ^s. The Rsp ^s (Responder-sensitive) locus in drive-sensitive Sd ⁺ spermatids has several hundred copies of a 240 bp satellite DNA repeat, whereas the Rsp ⁱ allele in insensitive spermatids has very few or no satellite repeats. The following model was proposed for Rsp's role (Genetics 193 771–784, 2013). Under non-distorting (i.e. SD⁺/SD⁺) conditions, precursor Rsp piRNA transcripts are exported from the nucleus, processed into mature piRNAs, and reenter the nucleus as part of a Rsp-piRNA–primed RNA–protein silencing complex (Rsp RNP) that silences the Rsp ^s locus and enables Rsp ^s-bearing chromosomes to condense chromatin. Under distorting (i.e. SD/SD⁺) conditions, perturbation of nuclear transport retains the Rsp precursor piRNAs in the nucleus, and/or blocks nuclear entry of the Rsp RNP. Consequently, Rsp ^s is not silenced, the Rsp ^s-bearing spermatids fail to condense chromatin, and are eliminated. In contrast, Rsp ⁱ spermatids can condense chromatin in either distorting or non-distorting conditions.

In fungi, meiotic drive was shown to propel species divergence (eLife 3 e02630, 2014), and Spore-killer genes that kill meiotic products not containing them are known (PNAS 109 12093–12098, 2012; PLOS Genet. 10 e1004387, 2014). We were excited to report yet another drive: crosses heterozygous for Neurospora crassa translocations introgressed into N. tetrasperma make fewer homokaryotic ascospores following alternate than adjacent-1 segregation (G3 5 1263–1272, 2015). Admittedly a more recondite finding, our referee was only trying to help us to disseminate it.

DURGADAS P KASBEKAR

Editor