Failure in male reproductive success is the predominant mode of hybrid breakdown among F2 hybrids between various Drosophila melanogaster populations. Left: F2 combined cross values and significance for average percent inviability (A), and for female (B) and male (C) reproductive failure rates. Line color denotes significance of differences in inviability/reproductive failure between-population’s crosses relative to both within-population cross groups, where pink indicates p < .05, yellow indicates .05< p < .1, and blue indicates p > .1. Within-population cross averages (gray) are listed adjacent to the population label. P-values were generated from bootstrapping (see Materials and methods section) and are listed underneath each between-population percentage. Individual cross averages are supplied in Supplementary Tables S1–S3. (D) Map of D. melanogaster population expansion and estimated divergence times from Sprengelmeyer et al. (2020). Divergence is given in thousands of years (kya) and each value represents the initial expansion estimate between nodes. Expansion out of ancestral ranges in southern-central African occurred roughly 12.8 kya. Populations rapidly colonized west Africa (12.6 kya), and later other regions of central Africa including our Ethiopian sample (9.5 kya). An additional estimated split (2.7 kya) between low- and high-altitude Ethiopian populations, the latter being used in the present study, is not depicted. Trans-Saharan migration occurred roughly 12.4 kya, during which populations experienced a moderately strong population bottleneck. Migration from the Middle East into cooler European regions occurred in the more recent past (1.8 kya). Coloration based on average annual temperature (scale bottom right) highlights the dramatic environmental differences between regions.