Genome complexity: reproductive molecules battle (Introduction)

by David Turell , Monday, April 10, 2023, 17:47 (383 days ago) @ David Turell

So-called 'selfish genes' fight in the reproductive process:

https://www.the-scientist.com/features/probing-selfish-centromeres-unveils-an-evolution...

"The Portuguese island of Madeira is home to six different chromosomal races of mice, each with dramatically reduced diploid chromosome numbers compared to mice elsewhere. This striking diversity, first identified at the turn of the 21st century, can be explained by the repeated fusions of separate chromosomes. Each race has a different set of fusions, and a hybrid between two races would likely have reduced fertility or be sterile because of problems with chromosome pairing. Such reproductive isolation among populations is a key step on the road to speciation—and in the mice’s case, these chromosomal changes have all occurred within the 1,000 years.

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"We usually think of the chromosome segregation machinery as ensuring unbiased, random segregation. As we learn in high school biology, if a diploid individual carries two different alleles of a gene (i.e., is heterozygous), then either allele is equally likely to end up in a haploid gamete. This law explains the 3:1 ratio of phenotypes that Mendel observed in his classic studies of heredity. Scientists have known for decades, however, that selfish genes can subvert Mendelian segregation to increase their frequency in the next generation, a phenomenon known as meiotic drive. The Madeira mice suggest that fusion chromosomes can also drive unequal inheritance.

"Because Rb fusions are easy to identify morphologically, and because mouse oocytes are an established model system, studying these fusions in mice provided an entry for my lab at the University of Pennsylvania to investigate the cell biology of meiotic drive, starting in 2010. Focusing on the centromere—the part of each chromosome that interacts with spindle microtubules to direct segregation in mitosis or meiosis—we found that the structure’s size determines the direction of biased segregation, with bigger centromeres preferentially segregating into the egg.

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"As a readout for functional asymmetry, we measured the position of the paired homologous chromosomes on the meiotic spindle. Chromosomes are positioned at the spindle equator when centromeres are functionally similar, as in a typical metaphase configuration, and off center when centromeres are functionally different. We found that chromosomes are positioned closer to the spindle equator when the kinetochore pathway is weakened, consistent with our prediction that the centromeres become functionally more similar. Conversely, when we weakened the heterochromatin pathway by knocking out the centromere protein CENP-B, which contributes to formation of heterochromatin near the centromere, we found that centromeres became functionally more different (i.e., more off center).

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"Thus, there appear to be competing parallel pathways: the kinetochore pathway exploited by selfish centromeres, and the heterochromatin pathway that promotes equal segregation. This means that proteins in both pathways can evolve to suppress drive by either weakening the kinetochore pathway or strengthening the heterochromatin pathway. Consistent with this prediction, by comparing rodent genomes in our study, we found signatures of adaptive evolution in components of both pathways, suggesting that changes in multiple centromere proteins can suppress the costs of drive.

"Our and other groups’ analyses are just beginning to probe the genetic conflict between selfish centromere DNA and rapidly evolving centromere proteins. We have experimental mouse model systems and a conceptual framework for drive and suppression, and we know which amino acid changes in centromere proteins have signatures of positive selection. We now face the challenge of designing experiments to dissect the functional consequences of these changes, which may be subtle."

Comment: to call competing molecular pathway 'selfish' returns to the stupidity of Dawkin's selfish gene mantra. What we are seeing is competing automatic molecular pathways, not competing human football teams! An interesting thought about possible speciation method.