Wild worm embryogenesis harbors ubiquitous polygenic modifier variation

• Published in: eLife Vol. 4
• Main Authors: Paaby, Annalise B, White, Amelia G, Riccardi, David D, Gunsalus, Kristin C, Piano, Fabio, Rockman, Matthew V
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 22.08.2015; eLife Sciences Publications, Ltd; eLife Sciences Publications Ltd
• Subjects: Animals; Caenorhabditis elegans; Caenorhabditis elegans - embryology; Caenorhabditis elegans - genetics; cryptic genetic variation; Embryonic Development; Genetic aspects; genetic background; Genetic Variation; Genomics and Evolutionary Biology; modifier variation; Multifactorial Inheritance; Observations; Phenotype; genomics; modifier variation; C. elegans; evolutionary biology; cryptic genetic variation; genetic background
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.09178

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture. Individuals of the same species have similar, but generally not identical, DNA sequences. This ‘genetic variation’ is due to random changes in the DNA—known as mutations—that occur among individuals. These mutations may be passed on to these individuals' offspring, who in turn pass them on to their descendants. Some of these mutations may have a positive or negative effect on the ability of the organisms to survive and reproduce, but others may have no effect at all. The process by which an embryo forms (which is called embryogenesis) follows a precisely controlled series of events. Within the same species, there is genetic variation in the DNA that programs embryogenesis, but it is not clear what effect this variation has on how the embryo develops. Here, Paaby et al. adapted a genetics technique called a ‘modifier screen’ to study how genetic variation affects the development of a roundworm known as Caenorhabditis elegans. The experiments show that populations of worms harbor a lot of genetic variation that affects how they tolerate the loss of an important gene. One by one, Paaby et al. interrupted the activity of specific genes that embryos need in order to develop. How this affected the embryo, and whether or not it was able to survive, was due in large part to the naturally-occurring genetic variation in other genes in these worms. Paaby et al.'s findings serve as a reminder that the effect of a mutation depends on other DNA sequences in the organism. In humans, for example, a gene that causes a genetic disease may produce severe symptoms in one patient but mild symptoms in another. Future experiments will reveal the details of how genetic variation affects embryogenesis, which may also provide new insights into how complex processes in animals evolve over time.