Heterotaxy inCaenorhabditis: widespread natural variation in left–right arrangement of the major organs

Abstract

Although the arrangement of internal organs in most metazoans is profoundly left–right (L/R) asymmetric with a predominant handedness, rare individuals show full (mirror-symmetric) or partial (heterotaxy) reversals. While the nematode Caenorhabditis elegans is known for its highly determinate development, including stereotyped L/R organ handedness, we found that L/R asymmetry of the major organs, the gut and gonad, varies among natural isolates of the species in both males and hermaphrodites. In hermaphrodites, heterotaxy can involve one or both bilaterally asymmetric gonad arms. Male heterotaxy is probably not attributable to relaxed selection in this hermaphroditic species, as it is also seen in gonochoristic Caenorhabditis species. Heterotaxy increases in many isolates at elevated temperature, with one showing a pregastrulation temperature-sensitive period, suggesting a very early embryonic or germline effect on this much later developmental outcome. A genome-wide association study of 100 isolates showed that male heterotaxy is associated with three genomic regions. Analysis of recombinant inbred lines suggests that a small number of loci are responsible for the observed variation. These findings reveal that heterotaxy is a widely varying quantitative trait in an animal with an otherwise highly stereotyped anatomy, demonstrating unexpected plasticity in an L/R arrangement of the major organs even in a simple animal.This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

Natural Variation and Genetic Determinants of Caenorhabditis elegans Sperm Size

“…In addition, increased levels of male-male competition in experimental contexts can lead to the evolution of larger male sperm size (LaMunyon and Ward 2002;Palopoli et al 2015), consistent with the relevance of sperm size for male competitive ability. Although self-fertilization is the predominant mode of C. elegans reproduction, with rare occurrence of males and outcrossing events in natural populations (Jovelin et al 2003; Barrière and Félix 2005;Sivasundar and Hey 2005), ample natural variation in diverse male traits exists (Hodgkin and Doniach 1997;Teotónio et al 2006;Palopoli et al 2008Palopoli et al , 2015Morran et al 2009;Anderson et al 2010;Noble et al 2015;Alcorn et al 2016), including male sperm size (Ward and Carrel 1979;LaMunyon and Ward 1995, 1998, 1999Murray et al 2011;Palopoli et al 2015). Moreover, gonochoristic (male-female) Caenorhabditis species exhibit, on average, much larger male sperm than the three androdioecious species, C. briggsae, C. elegans, and C. tropicalis, in which male-male competition is much weaker (LaMunyon and Ward 1999;Vielle et al 2016).…”

Evolution and Developmental System Drift in the Endoderm Gene Regulatory Network of Caenorhabditis and Other Nematodes

“…Most of our understanding of C. elegans biology is based on studies on a single genetic background, that of the laboratory reference strain N2. The identification of wild C. elegans isolates bearing distinct haplotypes has uncovered considerable phenotypic variation and developmental plasticity in this species (Hodgkin and Doniach, 1997;Harvey et al, 2008;Milloz et al, 2008;Andersen et al, 2012;Alcorn et al, 2016;Cook et al, 2016;Greene et al, 2016;Frézal et al, 2018;Gimond et al, 2019;Lee et al, 2019). Knocking down essential genes in the wild strains yielded distinct phenotypes and has uncovered substantial cryptic variation between the spectrum of isotypes (Paaby et al, 2015;Torres Cleuren et al, 2019).…”

Introduction to provocative questions in left–right asymmetry

“…Genetic analysis of heterotaxy is also being conducted by Alcorn et al [41], who use C. elegans in their search for disease loci. The commonly used laboratory strain of this nematode exhibits a stereotypical gut-gonad L/R asymmetry that has been shown to be established during early embryogenesis, i.e.…”

“…during the division of the two anterior granddaughter cells of four-cell stage embryo. In examining nearly 100 evolutionarily diverged isolates of this species, Alcorn et al [41] discovered that there is naturally existing variation in L/R organ asymmetry, and moreover, that some species exhibit heterotaxy in up to 11-12% of the animals. By conducting genetic crosses of lines showing normal L/R situs with lines showing heterotaxy, these investigators found that heterotaxy is associated with three genomic regions.…”