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Abstract Scholars and the public conceive of extraterrestrial life through the lens of life as we know it on Earth. However, assumptions based on centuries of study around heredity and evolution on Earth may not apply to life truly independent forms of life, and some perspectives accepted or ruled out in the nineteenth century may need to be re-evaluated for life outside of Earth. In honor of the 200th birthday of Mendel, and to provide raw material for the creativity of storytellers, filmmakers, and the public, this thought experiment essay revisits a handful of classic concepts and approaches, as well as some unusual forms of life on Earth, to posit whether different types of genetics and evolution may exist in truly independent extraterrestrial forms. While fundamental evolutionary processes like natural selection and genetic drift are likely to still apply at least similarly in independent life forms, inheritance may be quite radically different from that envisioned by Mendel and others since. 

For nearly a century, evolutionary biologists have observed chromosomes that cause lethality when made homozygous persisting at surprisingly high frequencies (>25%) in natural populations of many species. The evolutionary forces responsible for the maintenance of such detrimental mutations have been heavily debated—are some lethal mutations under balancing selection? We suggest that mutation–selection balance alone cannot explain lethal variation in nature and the possibility that other forces play a role. We review the potential that linked selection in particular may drive maintenance of lethal alleles through associative overdominance or linkage to beneficial mutations or by reducing effective population size. Over the past five decades, investigation into this mystery has tapered. During this time, key scientific advances have provided the ability to collect more accurate data and analyze them in new ways, making the underlying genetic bases and evolutionary forces of lethal alleles timely for study once more. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 11 is February 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.