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Essay: Studying Local Adaptation and Genetic Mapping in Zea Hybrids

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. 1 ABSTRACT 


. 18  Hybrid zones provide an excellent opportunity for studying local adaptation, hybrid zone 


. 19  dynamics, differential gene loss, and genetic mapping. The genus Zea, which contains the 


. 20  major world crop maize, contains many diverse wild taxa collectively called teosinte. Zea 


. 21  mays parviglumis, the lowland progenitor of maize, and Zea mays mexicana, its highland 


. 22  sister subspecies, live parapatrically with a few regions of range overlap. In these regions, 


. 23  putative hybrids have been identified in previous studies, but never deeply explored. Here 


. 24  we use a published 983 SNP dataset across 2,793 Zea individuals to identify and confirm a 


. 25  set of 112 Zea mays parviglumis and Zea mays mexicana hybrids, mostly clustered in three 


. 26  allopatric, genetically distinct hybrid groups in Central Mexico. Here we show that these 


. 27  hybrid groups have distinct environments that are intermediate between that of Zea mays 


. 28  parviglumis and Zea mays mexicana. We also provide evidence that these individuals are true 


. 29  hybrids and not ancestral to parviglumis and mexicana, or products of isolation by distance 


. 30  using multiple methods. This work expands on previous work by demonstrating that these 


. 31  plants are true hybrids, identifying hybrid groups and putative hybrid zones, and genetically 


. 32  characterizing the hybrid groups. With the potential for local adaptation, variable hybrid 


. 33  zone dynamics, and differential architectures of hybridization in all three populations, we 


. 34  present Zea as a great, natural model system for studying hybridization and hybrid zones. 


. 35  2 INTRODUCTION 


. 36  Gene flow can homogenize populations across a species range, but can also serve as major 


. 37  driver of evolutionary change, creating novel diversity that is then acted upon by selection 


. 38  (Ellstrand (2014)). Hybridization is the creation of genetically distinct individuals through 


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. 39  gene flow between differentiated populations; hybrid zones are regions where these differen- 


. 40  tiated populations come into secondary contact and reproduce (Barton & Hewitt (1985)). 


. 41  Hybrid zones have been detected in a diverse set of taxa including, for example, house mouse 


. 42  (Mus musculus Gim ́enez et al. (2016)), sunflower (genus Helianthus Rieseberg et al. (1999)), 


. 43  Oxford ragwort (genus Senecio Brennan et al. (2009)), Heliconius butterflies (genus Helico- 


. 44  nius Mallet et al. (1990)), and chickadees (genus Peocile Taylor et al. (2014)) The process 


. 45  of hybridization can enhance adaptability to novel conditions by increasing heterozygosity, 


. 46  producing new combinations of alleles and generating novel hybrid phenotypes (Abbott et al. 


. 47  (2013)). Genotypes in hybrid zones can be the result of numerous generations of hybridiza- 


. 48  tion and recombination and provide an opportunity for evolutionary studies of population 


. 49  dynamics, the timing of secondary contact of parental species, and unequal allele retention 


. 50  including variation in the genetic architecture of hybridization across replicate hybrid zones 


. 51  (Barton & Hewitt (1985); Smith & O’brien (2005)). 


52

. 53  Population dynamics in hybrid zones can vary substantially. For example, hybrid popula- 


. 54  tions can constitute a neutral intergradation zone when hybrids are not at a fitness advantage 


. 55  or disadvantage, a tension zone when hybrids have reduced fitness relative to their parents, 


. 56  or a selection-dependent (i.e. dispersal-independent) zone when hybrids show an increase in 


. 57  fitness within their natal environment (Barton & Hewitt (1985)). As deviations from neutral- 


. 58  ity, tension and selection-dependent zones have received the most theoretical consideration. 


. 59  (I’m not sure which of us wrote this last sentence, but it’s a sentence fragment and I’m not 


. 60  sure what the point was) Factors such as relative migration rate and population density, dif- 


. 61  ferential parental fitness and changing climate play a role in determining the size and shape 


. 62  of tension zones (Barton (1979); Key (1968); Buggs (2007); Barton & Hewitt (1985)). A 


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. 63  parental population with greater dispersal, population density, or overall fitness tends to 


. 64  push a tension zone away from itself by flooding the zone with its own genotypes (Barton 


. 65  (1979)). In contrast, selection-dependent zones are expected to be wider than tension zones 


. 66  due to increased fitness of hybrids (Barton & Hewitt (1985)) and are also more likely to 


. 67  spread beyond the region where gene flow initiated. Such hybrid populations that become 


. 68  physically isolated may ultimately speciate (Barton & Hewitt (1985) & Abbott et al. (2013)). 


. 69  For example, Pinus densata (High Mountain Pine), Senecio squalidus (Oxford Ragwort), and 


. 70  three species resulting from Helianthus annus x H. petiolaris (H. anomalus, H. deserticola, 


. 71  & H. paradoxus) were all born out of hybrid zones and subsequently occupied novel habi- 


. 72  tat, becoming isolated from parental populations (Abbott & Brennan (2014), Abbott et al. 


. 73  (2008), Rieseberg et al. (1998), & Heiser et al. (1969)). 


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. 75  Hybrid zones can be further characterized based on time since secondary contact of 


. 76  parental taxa. More recently developed zones will be comprised of hybrids with long tracts 


. 77  of admixture linkage disequilibrium (LD), which will, over time, be broken up by recombina- 


. 78  tion. The time since admixture of parental taxa can be estimated by evaluating admixture 


. 79  LD blocks through a process called “admixture deconvolution” or “ancestry painting” (Liang 


. 80  & Nielsen (2014)). The simplest model used to determine admixture timing assumes a single 


. 81  admixture event with LD tract lengths modeled under exponential decay (Liang & Nielsen 


. 82  (2014)). More complex models take into account multiple admixture events and source popu- 


. 83  lations, changing rates of gene flow into hybrid zones, and hybrid diffusion across geographic 


. 84  space (Hellenthal et al. (2014); Gravel (2012); Pool & Nielsen (2009); Sedghifar et al. (2015)). 


85

86 Finally, replicate hybrid zones can be viewed as pools of novel allele combinations upon 4

. 87  which selection can act. Patterns of parental allele loss and retention in hybrid populations 


. 88  can be characterized as genomic architectures of hybridization. Nonrandom architectures 


. 89  across hybrid individuals and populations provide evidence that a hybrid zone is selection 


. 90  dominated (i.e., dispersal independent; Barton & Hewitt (1985)). In the case where multiple 


. 91  hybrid zones are created by similar parental populations and distributed across an environ- 


. 92  mental gradient, different genomic architectures of hybridization have the potential to be 


. 93  locally adaptive. 


94

. 95  Here we establish teosinte (i.e., wild maize) as a promising system for the study of evo- 


. 96  lutionary dynamics in hybrid zones and, in particular, adaptive architectures of hybridiza- 


. 97  tion. The parental taxa of teosinte hybrids are the Mexican annual teosintes Zea mays 


. 98  ssp. parviglumis (hereafter parviglumis) and Zea mays ssp. mexicana (hereafter mexicana). 


. 99  Parviglumis, best known as the progenitor of domesticated maize (Zea mays ssp. mays; 


. 100  Matsuoka et al. (2002)), is found in the lowlands of southwest Mexico (<1800m) should it 


. 101  be ”Western Mexico” here?, and mexicana is distributed throughout the highlands of the 


. 102  Mexican Central Plateau (1600-2700m; Hufford et al. (2012)). The two subspecies diverged 


. 103  approximately 60,000 generations ago (Ross-Ibarra et al. (2009), & Hanson et al. (1996)) and 


. 104  differ in morphological features that suggest local adaptation. Parviglumis plants are green 


. 105  and glabrous, while mexicana individuals are more deeply pigmented and hairy. Differences 


. 106  in pigment and pilosity between parviglumis and mexicana are thought to be associated 


. 107  with adaptation across the altitudinal gradient in western Mexico (Wilkes (1967); Doebley 


. 108  (1984)). Pigmentation has previously been associated with cold tolerance in maize (Chong & 


. 109  Brawn (1969), & Doebley (1984)) and can be beneficial to high-altitude plants by improving 


. 110  their absorption of radiant solar energy (Galinat (1967), Chong & Brawn (1969)). Trichome 


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. 111  abundance has been associated with plants in cold climates generally (Daubenmire (1947); 


. 112  Bosabalidis & Sawidis (2014); Carlquist (1974)). In teosinte, Lauter et al. speculated that 


. 113  macrohairs indurated with silica may form a boundary layer that reduces the loss of absorbed 


. 114  radiant heat at high altitude (Lauter (2001) & Lauter et al. (2004)). 


115

. 116  Putative hybrids between these taxa have been reported at intermediate altitudes in re- 


. 117  gions of overlap in the distributions of parviglumis and mexicana (Fukunaga et al. (2005); 


. 118  Van Heerwaarden et al. (2011); Pyhajarvi et al. (2013)). The location of hybrids at inter- 


. 119  mediate altitudes is compelling since hybrid zones defined by altitude are often adaptive 


. 120  given the substantial environmental variation spanning altitudinal gradients (e.g., tempera- 


. 121  ture, atmospheric pressure, soil moisture, light intensity, and wind velocity (Korner (2007)). 


. 122  Moreover, teosinte hybrids have been documented across a region spanning hundreds of kilo- 


. 123  meters and several degrees of latitude in Mexico, which presents the opportunity for varying 


. 124  adaptive architectures of hybridization. To explore this system more fully and assess the 


. 125  evidence for multiple, independent hybrid zones we utilized a publicly available data set of 


. 126  983 SNPs genotyped in 2,793 individuals (Fang et al. (2012)). We additionally generated 


. 127  new data with 822 SNPs using the same genotyping platform across 239 individuals from 


. 128  12 populations The markers were not identical. That’s not clear here. Is that okay?. With 


. 129  these data we identify and confirm a set of 112 Zea mays parviglumis and Zea mays mexicana 


. 130  hybrids, residing in three allopatric, genetically distinct hybrid groups in the Central Plateau, 


. 131  the Central Balsas River Valley, and South Guerrero State of Mexico. The environments of 


. 132  these hybrid groups were all shown to be distinct and intermediate between that of Zea mays 


. 133  parviglumis and Zea mays mexicana. We present multiple independent sources of evidence 


. 134  that these plants are true hybrids and neither ancestral to parviglumis and mexicana, nor 


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. 135  products of IBD. Finally, we present this Mexican annual teosinte system as a great, all 


. 136  natural model system for studying hybridization and hybrid zones because of its potential 


. 137  for isolated local adaptation, variable hybrid zone dynamics, and differential architectures of 


. 138  hybridization in all three populations. 


139

. 140  3 MATERIALS & METHODS 


. 141  3.1 Generation of SNP Dataset 


. 142  Our starting dataset was a publicly available collection of 983 SNPs genotyped in 2,793 in- 


. 143  dividuals (Van Heerwaarden et al. (2010), Van Heerwaarden et al. (2011), & Fang et al. 


. 144  (2012)). From this extensive dataset we subsampled only parviglumis, mexicana and maize 


. 145  individuals relevant to our analyses. We retained only maize from Mexico since these lan- 


. 146  draces were most likely to have experienced gene flow with parviglumis and mexicana. The 


. 147  dataset was also filtered by first removing markers, then individuals, with ≥ 10% missing 


. 148  data. After data filtering, we retained 967 SNPs genotyped in 1344 individuals. 


. 149  3.2 Identifying Hybrids 


. 150  To determine whether an individual is substantially admixed, we first ran a STRUCTURE 


. 151  (version 2.3.4)(Pritchard et al. (2000)) analysis using all group size (k) values from two to 


. 152  eight, with 5,000 iterations of burnin and 10,000 MCMC repetitions, on all 1,344 teosinte 


. 153  and maize individuals in the published 967 SNP dataset. The curve of the likelihood asso- 


. 154  ciated with increases in k-values had mostly leveled out before reaching k=8. We therefore 


. 155  determined the highest group size did not need to be increased to find the best k-value. We 


. 156  then used the resulting likelihood values with the web Application, “Structure Harvester” 


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. 157  (version 0.6.93) (Earl & vonHoldt (2011)), to determine the best fitting k based on the deltaK 


. 158  statistic: the second order rate of change of the likelihood. The best k was determined to be 


. 159  three. We defined hybrids as individuals with greatest attribution to the teosinte subspecies 


. 160  they are annotated as and a significant (≥ 25%) attribution to the other teosinte. Teosinte 


. 161  with ≥ 90% self attribution were considered high confidence, non-admixed individuals. One 


. 162  plant resided among Central Balsas hybrids, had a parviglumis label, but had more mexicana 


. 163  attribution than parviglumis and therefore did not meet our definition of hybrid. Rather than 


. 164  make a subjective determination of the the status of this individual we removed it from the 


. 165  dataset. 


. 166  3.3 Environmental Data Extraction 


. 167  A custom R script, utilizing the package ”dismo” (version 1.1-1) using the BIOCLIM algo- 


. 168  rithm with 30 second resolution, was used to extract environmental data related to tempera- 


. 169  ture and precipitation based on the geographic coordinates of our hybrid individuals within 


. 170  hybrid groups as well as parviglumis and mexicana samples from our SNP dataset. 


. 171  3.4 Fst X Fst Calculations 


. 172  Wright’s Fst was determined with custom R and Python scripts using the R package “hierf- 


. 173  stat” (version 0.04-10). 60 Scatterplots were created using a custom R script comparing Fst 


. 174  values of each hybrid group (two at a time) vs each parent population (one at a time) for 


. 175  each of 10 chromosomes. 60 corresponding density plots were also created using a custom 


. 176  R script. The density plots show the distances of all points on each scatterplot to the y=x 


. 177  line. For each point this was done by creating a virtual point reflected across the y=x line 


. 178  by switching the x and y values. The Euclidean distance between the real and virtual points 


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. 179  was calculated, divided by two, then multiplied by -1 if the real point resides below the y=x 


. 180  line. 


. 181  3.5 Principle Component Analysis 


. 182  The Principle Component analysis was done with a custom R script using the package 


. 183  “prcomp” (from the “stats” package version 3.2.2). give credit to Joost script? I would 


. 184  cite the paper where this script was first used and I would explain how the script customizes 


. 185  the analysis beyond with prcomp can do Do you know what paper this was first used in? 


. 186  3.6 STRUCTURE Analysis with Both Datasets 


. 187  A STRUCTURE (version 2.3.4) analysis was performed using group sizes (k-values) from 


. 188  two to eight with 100,000 iterations of burnin and 1,000,000 MCMC repetitions both for 


. 189  the published 967 SNP dataset (Fang et al. (2012)) and for the generated 822 SNP dataset 


. 190  separtely. Three was chosen as the best k for both datasets using the deltaK method (Earl & 


. 191  vonHoldt (2011)). Also, using k ̄3 three randomly selected members of each each population 


. 192  of high-confidence parviglumis, high-confidence mexicana, and Mexican maize from the 967 


. 193  SNP dataset and each population from the 822 SNP dataset were used to test the effects 


. 194  of subsampling on STRUCTURE results. Five biological replicates were ran using k ̄3, 3,000 


. 195  iterations of burnin and 10,000 MCMC repetitions and the highest mean ln likelihood repe- 


. 196  tition was chosen for presentation. Plots were generated using the program distruct (version 


. 197  1.1) (Rosenberg et al. (2002)). 


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. 198  3.7 Inversion Analyses 


. 199  Wright’s Fst (Wright (1952)) was calculated with custom R and Python scripts using the 


. 200  R package “hierfstat” (version 0.04-10) comparing high-confidence parviglumis and mexi- 


. 201  cana samples. Markers with an Fst greater than 0.7 were extracted using a custom Python 


. 202  script. Four markers were then identified as high-confidence inv4m markers (PZD00030.4, 


. 203  PZA01637.3, PZA01637.4, and PZD00030.1), meaning that they lie within the well known 


. 204  inversion on chromosome Four, citation here, any ideas Matt? Where was it first identi- 


. 205  fied?, and they have >0.95 Fst values. Using another custom Python script, these loci were 


. 206  examined in all high-confidence parviglumis and mexicana samples and a parviglumis and 


. 207  mexicana type were identified or each locus based on allele frequencies within each subspecies. 


. 208  Each individual was then analyzed using a custom Python script, and had one of five possible 


. 209  mutually exclusive inversion states assigned to it based on genotypes at these loci. 


210

. 211  The frequency of the mexicana inversion types per sampling site was plotted against alti- 


. 212  tude. This frequency was calculated by summing, for each sampling site, mexicana inversion 


. 213  types weighted as two, parviglumis types weighted as zero, and heterozygotes types weighted 


. 214  as one normalized by 2N where N is the sum of mexicana, parviglumis and heterozygous in- 


. 215  version types in the sampling site. In order to be considered as having “mixed” hybrid status 


. 216  a sampling site must have at least 20% minority hybrid status individuals. The highest Fst 


. 217  SNP on inv4m between high confidence parviglumis and high confidence mexicana was also 


. 218  determined in order to look at the inversion data in terms of allele frequencies. 


219

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. 220  3.8 ConStruct Analysis 


. 221  The program conStruct (version beta) was used to generate a STRUCTURE-like q-matrix 


. 222  explicitly controlling for isolation by distance. Because the package is not designed for high 


. 223  numbers of individuals and cannot run with more individuals than SNPS, we randomly sub- 


. 224  sampled one individual from each parviglumis, mexicana, and hybrid accession reducing the 


. 225  data to 195 individuals. Using these individuals we ran the program under the spatial model 


. 226  using default parameters. We ran conStruct at group size two with five replicates, then used 


. 227  the output from the highest likelihood replicate to determine the percent attribution to the 


. 228  alternative teosinte for each group, where the alternative teosinte is the mexicana annual 


. 229  teosinte that does not match the individual’s taxonomic description. The groups used to 


. 230  make the alternative attribution table were high-confidence parviglumis, ambiguous parvig- 


. 231  lumis, high-confidence, high-confidence mexicana, ambiguous mexicana, all hybrids, Central 


. 232  Plateau hybrids, Central Balsas hybrids, and South Guerrero hybrids. 


233

. 234  4 RESULTS 


. 235  4.1 Identifying Hybrids and Hybrid Groups 


. 236  To identify hybrids, we used the program STRUCTURE with a subset of a publicly avail- 


. 237  able SNP dataset (Van Heerwaarden et al. (2010), Van Heerwaarden et al. (2011), & Fang 


. 238  et al. (2012)) that includes 967 SNPs genotyped in 1,344 individuals. STRUCTURE uses 


. 239  a model-based approach to infer population structure and assign individuals to populations 


. 240  probabilistically (Pritchard et al. (2000)). STRUCTURE results (Figure 4), suggested that 


. 241  the population structure of maize and the Mexican annual teosintes, together, was best de- 


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. 242  scribed as having three groups: parviglumis, mexicana, and maize. This aligns perfectly with 


. 243  the taxonomic descriptions assigned to these individuals. Within each taxonomic group, in- 


. 244  dividuals were sorted from lowest to highest altitude. Many of the admixed individuals in 


. 245  both teosinte subspecies were the individuals closest in altitude to the altitudinal distribution 


. 246  of the other subspecies, and were therefore more likely to have come into contact with and 


. 247  potentially admixed with the other subspecies (Figures 4 & 20). 


248

. 249  We plotted all 1344 individuals on a map of Mexico (Figure 5). We also used the q-matrix 


. 250  from STRUCTURE to make a map of Mexico with pie charts representing hybrid individuals 


. 251  and their genome-wide attribution to the three taxonomic groups (Figure 6). Using this data 


. 252  we identified 112 high-confidence hybrids, 634 high-confidence non-admixed parviglumis in- 


. 253  dividuals, 95 high-confidence non-admixed mexicana individuals, as well as 176 parviglumis 


. 254  and 51 mexicana individuals that showed evidence of admixture, but did not pass the thresh- 


. 255  old to be considered high-confidence hybrids. Most high-confidence hybrids were among three 


. 256  groups of clustered hybrid populations in Mexico: one in the Central Plateau (CPG), one in 


. 257  the Central Balsas River Valley (CBG), and one in Southern Guerrero State (SGG) (Figure 


. 258  5). Relatedly, the putative hybrid zones they reside in will be referred to as the CPZ, CBG, 


. 259  and SGZ respectively. These hybrid groups varied substantially in the number of individuals 


. 260  sampled: 4 in the CPG, 84 in the CBG, and 14 in the SGG. Note that this was not all 


. 261  admixed individuals in these areas, but rather those found using our SNP dataset which also 


. 262  passed our high threshold for being labeled high-confidence hybrids. The hybrid groups also 


. 263  differed in their general pattern of attribution to parviglumis, mexicana and Mexican maize. 


. 264  The CPG showed greatest attribution to mexicana, the SGG showed greatest attribution to 


. 265  parviglumis, and the CBG showed greatest attribution to parviglumis, much attribution to 


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266 mexicana, and some to maize. 267

. 268  In addition to the CPG,CBG, and SGG, other hybrids were identified including those 


. 269  from a sampling location East of the CBG and North of the SGG called Ahuacatitlan (Fig- 


. 270  ure 6). This population was noteworthy as a previously studied mexicana-parviglumis hybrid 


. 271  population (Fukunaga et al. (2005) & Pyhajarvi et al. (2013)). For this reason, we wanted 


. 272  to include the population as part of either the CBG or SGG if it was appropriate. We also 


. 273  needed a more rigorous method for determining hybrid groups than geographic ranges in 


. 274  order to ensure that each group is genetically distinct and showed within-group genetic simi- 


. 275  larity. In order to solve both problems concurrently, we ran a Principle Component Analysis 


. 276  (PCA) with all parviglumis, mexicana, and hybrid samples. 


277

. 278  4.2 Confirming Hybrid Grouping 


. 279  The PCA showed clear clustering of all Zea subspecies as well as hybrids broadly and all 


. 280  hybrid groups indicating common ancestry within each hybrid group and genetic differen- 


. 281  tiation between groups (Figure 7). This validates both our threshold for identifying high 


. 282  confidence hybrids as well as our grouping of these hybrids. As for the Ahuacatitlan pop- 


. 283  ulation, we found they form their own cluster separate from the CBG and the SGG. We 


. 284  therefore concluded that the Ahuacatitlan plants could not reasonably be considered a part 


. 285  of any of the hybrid groups identified here. For this reason, together with the fact they 


. 286  represented only one sampling location, we decided to consider the Ahuacatitlan samples as 


. 287  part of the “other hybrids” category. PC1 distinguished between parviglumis and mexicana 


. 288  with hybrids inhabiting the space between, while PC2 distinguished between the CBG and 


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. 289  parent samples. We also made a biplot of both samples and SNPs on PCs one and two and 


. 290  found that among the top 10 SNPs, in terms of vector magnitude, were one SNP on the large 


. 291  inversion on chromosome3 (citation here for chr3 inversion), five SNPs on inv4m (citation 


. 292  here for inv4m), and one SNP located on the ZMM4 gene, a MADS-box gene which affects 


. 293  flowering time and development (Danilevskaya et al. (2008)) (Figures 8 & 25). In fact, four 


. 294  of the five SNPs on inv4m were the top four SNPs in the entire dataset by this measure 


295

. 296  We wondered whether the CBG’s increased genetic differentiation from its parent sub- 


. 297  species could be explained by its unique STRUCTURE attribution to maize (Figure 6). To 


. 298  test this we reran the PCA with maize as part of the dataset. We found that when maize 


. 299  was incorporated into the PCA (Figure 9) the CBG did not cluster with maize, and was not 


. 300  closer to maize than all other teosinte samples. We therefore could not conclude that the 


. 301  CBG’s place in the original PCA was due to genetic relatedness to maize. Here PC1 seemed 


. 302  to explain the differentiation between teosinte and maize, and PC2 seemed to distinguish 


. 303  between parviglumis/maize and mexicana with all hybrids clustering with teosinte relative 


. 304  to PC1 and inhabiting the center with regards to PC2. 


305

. 306  4.3 Confirming Hybrid Identification 


. 307  In order to determine whether our hybrids are true hybrids, and not merely products of Iso- 


. 308  lation by Distance (IBD) we performed a STRUCTURE analysis using k values from two to 


. 309  eight on known parviglumis, mexicana, and hybrid populations from our generated 822 SNP 


. 310  dataset and separately with our 967 SNP dataset. In both cases 100,000 iterations of burnin 


. 311  and 1,000,000 MCMC repetitions were used in order to generate results of the highest quality. 


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