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Brady, M. J.

Publications and source records attributed to Brady, M. J..

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Genetic and environmental influences on the distributions of three chromosomal drive haplotypes in maize

Meiotic drive elements are regions of the genome that are transmitted to progeny at frequencies that exceed Mendelian expectations, often to the detriment of the organism. In maize there are three prevalent chromosomal drive elements known as Abnormal chromosome 10 (Ab10), K10L2, and the B chromosome. There has been much speculation about how these drivers might interact with each other and the environment in traditional maize landraces and their teosinte ancestors. Here we used genotype-by-sequencing data to score more than 10,000 maize and teosinte lines for the presence or absence of each driver. Less than [~]0.5% of modern inbred lines carry chromosomal drivers. Among individuals from 5331 open-pollinated landraces, 6.32% carried Ab10, 5.16% carried K10L2, and 12.28% carried at least one B chromosome. Using a GWAS approach we identified unlinked loci that associate with the presence or absence of the selfish genetic elements. Many genetic modifiers are positively associated with the drivers, suggesting that there may have been selection for alleles that ameliorate their negative fitness consequences. We then assessed the contributions of population structure, associated loci, and the environment on the distribution of each chromosomal driver. There was no significant relationship between any chromosomal driver and altitude, contrary to conclusions based on smaller studies. Our data suggest that the distribution of the major chromosomal drivers is primarily influenced by neutral processes and the deleterious fitness consequences of the drivers themselves. While each driver has a unique relationship to genetic background and the environment, they are largely unconstrained by either. AUTHOR SUMMARYMeiotic drivers are selfish genetic elements that are transmitted to progeny at frequencies that exceed what is expected by chance. There are three such meiotic drivers in maize known as Ab10, K10L2 and the B chromosome. Prior data indicate that each driver lowers plant fitness to some degree, partially explaining the fact that they are usually observed at low frequencies, but the impact of environment and genetic modifiers has not been investigated. Here we identified the presence or absence of each driver using low coverage sequencing data from over 10,000 maize inbreds, open pollinated landraces, and accessions of teosinte -- the grass-like ancestor of maize. We found that they exist at 5-12% frequencies in open pollinated varieties, but are rare in modern inbreds. We went on to use location data to assess the impact of environmental variables on their distribution, and applied genome-wide association methods to look for genetic modifiers that might contribute to their prevalence. We found that neither the environment nor genetic modifiers have strong influences on the distribution of the three meiotic drive elements, suggesting that their low but consistent frequencies are determined primarily by the fitness consequences of the drivers themselves.

genetics↗

Antagonistic kinesin-14s within a single chromosomal drive haplotype

In maize, there are two meiotic drive systems that operate on large tandem repeat arrays called knobs that are found on chromosome arms. One meiotic drive haplotype, Abnormal chromosome 10 (Ab10), encodes two kinesin proteins that interact with two distinct tandem repeat arrays in a sequence-specific manner to confer meiotic drive. The kinesin KINDR associates with knob180 repeats while the kinesin TRKIN associates with TR-1 repeats. Prior data show that meiotic drive is conferred primarily by the KINDR/knob180 system, with the TRKIN/TR-1 system having little or no role. The second meiotic drive haplotype, K10L2, shows low levels of meiotic drive and only encodes the TRKIN/TR-1 system. Here we used long-read sequencing to assemble the K10L2 haplotype and showed that it has strong homology to an internal portion of the Ab10 haplotype. We also carried out CRISPR mutagenesis of Trkin to test the role of Trkin on Ab10 and K10L2. The data indicate that the Trkin gene on Ab10 does not improve drive or fitness but instead has a weak deleterious effect when paired with a normal chromosome 10. The deleterious effect is more severe when Ab10 is paired with K10L2: in this context functional Trkin on either chromosome nearly abolishes Ab10 drive. We modeled the effect of Trkin on Ab10 and found it should not persist in the population. We conclude that Trkin either confers an advantage to Ab10 in untested circumstances or that it is in the process of being purged from the Ab10 population. ARTICLE SUMMARYMendels first law states that paired chromosomes are transmitted through meiosis at equal frequencies. Some chromosome variants, however, are transmitted at higher frequencies in a process called meiotic drive. We wanted to know the function of a motor protein called TRKIN that is encoded on a maize meiotic drive chromosome. Surprisingly, we found that TRKIN provides no advantage to the meiotic driver and instead seems to be deleterious, suggesting it had a function in a wild ancestor but is now being purged from the population. The results illustrate how genomes are shaped by often-conflicting forces of selection and selfish genetic elements.

evolutionary biology↗

The maize striate leaves2 (sr2) gene encodes a conserved DUF3732 domain homologous to the rice yss1 gene

Maize striate leaves2 (sr2) is a mutant that causes white stripes on leaves that has been used in mapping studies for decades, though the underlying gene has not been identified. The sr2 locus has been previously mapped to small regions of the normal chromosome 10 (N10) and a rearranged variant called Abnormal Chromosome 10 (Ab10). A comparison of assembled genomes carrying N10 and Ab10 revealed only five candidate sr2 genes. Analysis of a stock carrying the sr2 reference allele (sr2-ref) showed that one of the five genes has a transposon insertion that disrupts its protein sequence and has a severe reduction in mRNA. An independent Mutator transposon insertion in the gene (sr2-Mu) failed to complement the sr2-ref mutation, and plants homozygous for sr2-Mu showed white striped leaf margins. The sr2 gene encodes a DUF3732 protein with strong homology to a rice gene with a similar mutant phenotype called young seedling stripe1 (yss1). These and other published data suggest that sr2 may have a function in plastid gene expression.

genetics↗

Mutational Landscape of Spontaneous Base Substitutions and Small Indels in Experimental Caenorhabditis elegans Populations of Differing Size

Experimental investigations into the rates and fitness effects of spontaneous mutations are fundamental for our understanding of the evolutionary process. To gain insights into the molecular and fitness consequences of spontaneous mutations, we conducted a mutation accumulation (MA) experiment at varying population sizes in the nematode Caenorhabditis elegans, evolving 35 lines in parallel for 409 generations at three population sizes (N = 1, 10, 100 individuals). Here, we focus on nuclear SNPs and small indels under minimal influence of selection, as well as their accrual rates in larger populations under greater selection efficacy. The spontaneous rates of base substitutions and small indels are 1.84 x 10-9 substitutions and 6.84 x 10-10 changes /site/generation, respectively. Small indels exhibit a deletion-bias with deletions exceeding insertions by three-fold. Notably, there was no correlation between the frequency of base substitutions, nonsynonymous substitutions or small indels with population size. These results contrast with our previous analysis of mtDNA mutations and nuclear copy-number changes in these MA lines, and suggest that nuclear base substitutions and small indels are under less stringent purifying selection compared to the former mutational classes. A transition bias was observed in exons as was a near universal base substitution bias towards A/T. Strongly context-dependent base substitutions, where 5-T and 3-As increase the frequency of A/T [->] T/A transversions, especially at the boundaries of A or T homopolymeric runs, manifest as higher mutation rates in (i) introns and intergenic regions relative to exons, (ii) chromosomal cores versus arms and tips, and (iii) germline-expressed genes.

evolutionary biology↗