September GENETICS Highlights
This Month’s Centennial Articles
Sydney Brenner on the genetics of Caenorhabditis elegans, pp. 1-2
Associate Editor Bob Goldstein introduces the 1974 Classic reporting Sydney Brenner’s first Caenorhabditis elegans mutant screens, stimulating discoveries from thousands of researchers that have impacted the breadth of biology and biomedical science.
Barbara McClintock on defining the unstable genome, pp. 3-4
Marnie E. Halpern
Associate Editor Marnie Halpern introduces Barbara McClintock’s 1953 Classic describing how so-called “extragenic” components (now known as transposons) could alter the function of nearby genes. Thirty years later she would be the sole winner of the Nobel Prize in Physiology or Medicine for her scrupulous studies of unexpected phenotypic changes in maize, and the insight that led to her discovery of mobile genetic elements.
Teaching genetics: past, present, and future, pp. 5-10
Michelle K. Smith and William B. Wood
Undergraduate genetics teaching has changed in many ways over the past century Compared to those of 100 years ago, contemporary genetics courses are broader in content and increasingly are taught differently, using instructional techniques based on educational research and constructed around the principles of active learning and backward design. Future courses can benefit from wider adoption of these approaches, more emphasis on the practice of genetics as a science, and new methods of assessing student learning.
Medical genetics and the first studies of the genetics of populations in Mexico, pp. 11-19
During the post-WWII emphasis on studying the genetic composition of populations, Mexico was one of the major research hubs. In this Centennial Perspectives article, Ana Barahona discusses the work of three leading players in this story: Mario Salazar Mallen, Adolfo Karl, and Ruben Lisker. Lisker’s studies were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population.
Bayesian inference of the evolution of a phenotype distribution on a phylogenetic tree, pp. 89-98
M. Azim Ansari and Xavier Didelot
Many traits are determined by a mixture of genetic and environmental factors. Ansari and Didelot model the evolution of the probability of a trait being observed, rather than the evolution of the trait itself. Reconstructing the history of this trait distribution reveals when and to what extent genetic factors affected the trait. A phylogenetic tree can therefore be divided into parts within which the trait probability is constant. The authors apply the method to real data from HIV immunology and bacterial ecology.
Remarkably long-tract gene conversion induced by fragile site instability in Saccharomyces cerevisiae, pp. 115-128
Shahana A. Chumki, Mikael K. Dunn, Thomas F. Coates, Jeanmarie D. Mishler, Ellen M. Younkin, and Anne M. Casper
Loss of heterozygosity (LOH) in human tumors is strongly correlated with break-prone chromosomal locations called common fragile sites. Gene conversion is one cause of LOH. Chumki et al. report that gene conversion is increased 48- to 62-fold by instability at the yeast fragile site FS2. The tract characteristics suggest a prominent mechanism for fragile site repair is break-induced replication that switches templates (dBIR). Thus, dBIR is likely to drive common fragile site-stimulated LOH in human tumors.
The genetic basis of natural variation in Caenorhabditis elegans telomere length, pp. 371-383
Daniel E. Cook, Stefan Zdraljevic, Robyn E. Tanny, Beomseok Seo, David D. Riccardi, Luke M. Noble, Matthew V. Rockman, Mark J. Alkema, Christian Braendle, Jan E. Kammenga, John Wang, Leonid Kruglyak, Marie-Anne Félix, Junho Lee, and Erik C. Andersen
Despite the importance of telomeres to genome stability, their length varies significantly between individuals. Cook et al. characterize natural variation in telomere lengths in Caenorhabditis elegans and map that variation to a polymorphism in a gene encoding a telomere-regulatory factor. They show that telomere length variation has little fitness consequence in the laboratory and find no evidence of selection at the regulatory locus in wild populations. These results suggest that telomere lengths beyond a basal level are not advantageous in wild populations.
Fast-flowering mini-maize: seed to seed in 60 days, pp. 35-42
Morgan E. McCaw, Jason G. Wallace, Patrice S. Albert, Edward S. Buckler, and James A. Birchler
McCaw et al. developed two Zea mays lines as a short-generation model for maize. Five generations per year of Fast-Flowering Mini-Maize (FFMM) can be achieved routinely with reduced greenhouse space, as opposed to two to three for traditional lines. Phenotypic kernel mutations have been introduced into one line to facilitate genetic analysis and demonstration of Mendelian principles in an educational setting. A whole genome resequence of one line, aligned to the B73 reference genome, is also reported.
Detecting heterogeneity in population structure across the genome in admixed populations, pp. 43-56
Caitlin McHugh, Lisa Brown, and Timothy A. Thornton
Ancestry patterns are often assumed to be similar across the genome. Previous studies have suggested that systematic ancestry differences in admixed populations may arise due to selection and/or sex-specific patterns of non-random mating. McHugh et al. propose the CAnD method for detecting heterogeneity in population structure genome-wide. Application of CAnD to HapMap Mexican American (MXL) samples provides strong evidence of heterogeneity in population structure (p=1e-05), largely driven by elevated Native American ancestry on the X chromosome as compared to the autosomes.
Histone deacetylases with antagonistic roles in Saccharomyces cerevisiae heterochromatin formation, pp. 177-190
Deborah M. Thurtle-Schmidt, Anne E. Dodson, and Jasper Rine
Saccharomyces cerevisiae silent mating loci have been a paradigm for studying heterochromatin formation, yet an interesting conundrum has plagued the Sir-silencing model. The only known role for Sir2 in silencing is to deacetylate H4K16, however preemptively blocking this acetylation does not restore silencing in Sir2 mutants. Thurtle-Schmidt et al. found that restoration of silencing depends on two deacetylases, Rpd3 and Hst3, independent of their known histone substrates, revealing unexpected and antagonistic roles for multiple deacetylases in Sir protein-based silencing.
Fine-scale human population structure in southern Africa reflects ecogeographic boundaries, pp. 303-314
Caitlin Uren, Minju Kim, Alicia R. Martin, Dean Bobo, Christopher R. Gignoux, Paul D. van Helden, Marlo Möller, Eileen G. Hoal, and Brenna M. Henn
The African KhoeSan populations have remained largely isolated until about 2,000 years ago. Though dozens of KhoeSan groups exist, very little is known about their population history. Uren et al. examine fine-scale population structure in southern Africa and find it does not always correspond to linguistic or subsistence categories as previously suggested, but rather reflects the role of geographic barriers and the ecology of the greater Kalahari Basin. The authors conclude that local adoption of pastoralism, at least by the Nama, appears to have been primarily a cultural process with limited genetic impact from eastern Africa.
Genetic architecture of domestication-related traits in maize, pp. 99-113
Shang Xue, Peter J. Bradbury, Terry Casstevens, and James B. Holland
Domestication radically transformed the morphology of maize compared to its wild ancestor, teosinte. Nevertheless, some of the traits presumed to be important under domestication retain variation in maize. Xue et al. tested if this variation is due to genes in regions known to differentiate maize and teosinte. They found no major effect loci remaining, but many small effect genes outside of the known domestication genome regions affect variation in domestication-related traits.