Chromosomal inversions play an important role in local adaptation. Inversions can capture multiple locally adaptive functional variants in a linked block by repressing recombination. However, this recombination suppression makes it difficult to identify the genetic mechanisms that underlie an inversion's role in adaption.In this study, we explore how large-scale transcriptomic data can be used to dissect the functional importance of a 13 Mb inversion locus (Inv4m) found almost exclusively in highland populations of maize (Zea mays ssp. mays). Inv4m introgressed into highland maize from the wild relative Zea mays ssp.mexicana, also present in the highlands of Mexico, and is thought to be important for the adaptation of these populations to cultivation in highland environments. First, using a large publicly available association mapping panel, we confirmed that Inv4m is associated with locally adaptive agronomic phenotypes, but only in highland fields. Second, we created two families segregating for standard and inverted haplotypess of Inv4m in a isogenic B73 background, and measured gene expression variation association with Inv4m across 9 tissues in two experimental conditions. With these data, we quantified both the global transcriptomic effects of the highland Inv4m haplotype, and the local cis-regulatory variation present within the locus. We 1/33 found diverse physiological effects of Inv4m, and speculate that the genetic basis of its effects on adaptive traits is distributed across many separate functional variants. Author SummaryChromosomal inversions are an important type of genomic structural variant. However, mapping causal alleles within their boundaries is difficult because inversions suppress recombination between homologous chromosomes. This means that inversions, regardless of their size, are inherited as a unit. We leveraged the high-dimensional phenotype of gene expression as a tool to study the genetics of a large chromosomal inversion found in highland maize populations in Mexico -Inv4m. We grew plants carrying multiple versions of Inv4m in a common genetic background, and quantified the transcriptional reprogramming induced by alternative alleles at the locus. Inv4m has been shown in previous studies to have a large effect on flowering, but we show that the functional variation within Inv4m affects many developmental and physiological processes.Chromosomal inversions are structural rearrangements that form when a portion of a chromosome breaks in 2 two places and reinserts in the opposite orientation. The reversed order of loci prevent recombination with 3 the non-inverted homologous chromosome, as crossover products are imbalanced and often non-viable [1]. 4This spontaneous, long-distance genetic linkage is important for speciation and local adaptation because it 5 can capture multiple adaptive and potentially interacting loci in a single haplotype [2][3][4]. Inversions are 6 common across taxa [1], often pre-date speciation events, and can spread through admixture [5,6]. They 7 have been link...

Chromosomal inversions play an important role in local adaptation. Inversions can capture multiple locally adaptive functional variants in a linked block by repressing recombination. However, this recombination suppression makes it difficult to identify the genetic mechanisms underlying an inversion’s role in adaptation. In this study, we used large-scale transcriptomic data to dissect the functional importance of a 13 Mb inversion locus (Inv4m) found almost exclusively in highland populations of maize (Zea mays ssp. mays). Inv4m was introgressed into highland maize from the wild relative Zea mays ssp. mexicana, also present in the highlands of Mexico, and is thought to be important for the adaptation of these populations to cultivation in highland environments. However, the specific genetic variants and traits that underlie this adaptation are not known. We created two families segregating for the standard and inverted haplotypes of Inv4m in a common genetic background and measured gene expression effects associated with the inversion across 9 tissues in two experimental conditions. With these data, we quantified both the global transcriptomic effects of the highland Inv4m haplotype, and the local cis-regulatory variation present within the locus. We found diverse physiological effects of Inv4m across the 9 tissues, including a strong effect on the expression of genes involved in photosynthesis and chloroplast physiology. Although we could not confidently identify the causal alleles within Inv4m, this research accelerates progress towards understanding this inversion and will guide future research on these important genomic features.

BackgroundThe amino acid sequence of a protein is the blueprint from which its structure and ultimately function can be derived. Therefore, sequence comparison methods remain essential for the determination of similarity between proteins. Traditional approaches for comparing two protein sequences begin with strings of letters (amino acids) that represent the sequences, before generating textual alignments between these strings and providing scores for each alignment. When the similitude between the two protein sequences to be compared is low however, the quality of the corresponding sequence alignment is usually poor, leading to poor performance for the recognition of similarity.ResultsIn this study, we develop an alignment free alternative to these methods that is based on the concept of string kernels. Starting from recently proposed kernels on the discrete space of protein sequences (Shen et al, Found. Comput. Math., 2013,14:951-984), we introduce our own version, SeqKernel. Its implementation depends on two parameters, a coefficient that tunes the substitution matrix and the maximum length of k-mers that it includes. We provide an exhaustive analysis of the impacts of these two parameters on the performance of SeqKernel for fold recognition. We show that with the right choice of parameters, use of the SeqKernel similarity measure improves fold recognition compared to the use of traditional alignment-based methods. We illustrate the application of SeqKernel to inferring phylogeny on RNA polymerases and show that it performs as well as methods based on multiple sequence alignments.ConclusionWe have presented and characterized a new alignment free method based on a mathematical kernel for scoring the similarity of protein sequences. We discuss possible improvements of this method, as well as an extension of its applications to other modeling methods that rely on sequence comparison.

Maize is a staple food of smallholder farmers living in highland regions up to 4,000 meters above sea level worldwide. Mexican and South American highlands are two major highland maize growing regions, and population genetic data suggests the maize’s adaptation to these regions occurred largely independently, providing a case study for convergent evolution. To better understand the mechanistic basis of highland adaptation, we crossed maize landraces from 108 highland and lowland sites of Mexico and South America with the inbred line B73 to produce F1 hybrids and grew them in both highland and lowland sites in Mexico. We identified thousands of genes with divergent expression between highland and lowland populations. Hundreds of these genes show patterns of convergent evolution between Mexico and South America. To dissect the genetic architecture of the divergent gene expression, we developed a novel allele-specific expression analysis pipeline to detect genes with divergent functional cis-regulatory variation between highland and lowland populations. We identified hundreds of genes with divergent cis-regulation between highland and lowland landrace alleles, with 20 in common between regions, further suggesting convergence in the genes underlying highland adaptation. Further analyses suggest multiple mechanisms contribute to this convergence in gene regulation. Although the vast majority of evolutionary changes associated with highland adaptation were region-specific, our findings highlight an important role for convergence at the gene expression and gene regulation levels as well.