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The “Why” of the Fly “Y”: Reflections on “Junk” DNA

Richard Sternberg

junk DNA

In April 1980, almost exactly forty years ago, the journal Nature published a pair of highly influential articles on the topic of what has become known as “junk” or “selfish” DNA. Both reflected the key concept of The Selfish Gene, the highly influential 1976 book by Richard Dawkins, namely, that organisms are merely DNA’s way of making more DNA. The first was authored by W. Ford Doolittle and Carmen Sapienza and titled “Selfish genes, the phenotype paradigm and genome evolution.”1 The second was authored by Leslie Orgel and Francis Crick and titled “Selfish DNA: the ultimate parasite.”2 Together they posited an easy-to-grasp way to conceive of “excess” nucleotides along chromosomes — repetitive sequences in general and transposable elements in particular. In short, it was proposed that most such DNA elements neither had nor have (developmental) effects or functions (in general) in the shaping of an organism’s traits (its “phenotype”). And because they have “no phenotypic expression” (as Doolittle and Sapienza put it) or “little or no effect on the phenotype” (as Orgel and Crick put it), the only role that can be ascribed to them is that of replicative survival.

Bond-Servant of Genetics

But there are two problems with this outlook, one empirical and one formal. That which is empirical involves the organization of (eukaryotic) chromosomes, whereas that which is formal involves how to define “effect,” “expression,” and “function” when it comes to repetitive DNA sequences of any type. And so to narrow our focus on these problems, let us give some thought to the Y chromosome of Drosophila melanogaster, that engaging fly which is the bond-servant of genetics, as it is replete with a “junk” and “selfish” typography. Note that I will only be briefly touching on the first problem in this piece.

  Now the Y chromosome of this species is approximately 40,000,000 bases in length, and that is significant for it makes up around 20 percent of the male haploid DNA content.3-4 While it is essential for male fertility, it has but few protein-coding regions and these are interrupted by or surrounded by vast tracks of (often degenerated) transposable elements, tandemly arranged runs of “satellite” units (such as AACAC, AATAG, AATAT, and so forth), a block of ribosomal-RNA genes, and various other sequence families.5 In addition, its various components are densely compacted in somatic-cell nuclei, and this “heterochromatin” is supposedly “inert” until around the stage the primary spermatocytes are formed. I hasten to mention also that its composition of DNA varies from strain to strain of D. melanogaster, even though its protein-coding sequences are stable throughout.6 What all of this seems to suggest, then, is that the bulk of this chromosome may have “no phenotypic expression” or “little or no effect on the phenotype” in males of this species.

The Empirical Problem

Recall, however, that I said that there are two problems with this outlook, one of which is empirical. Concerning that, let us note that by the mid 1950s it was well-established that introducing a Y chromosome into a female D. melanogaster (by the feats of fruit-fly genetics) leads to a broad range of phenotypic effects, as does increasing the copies or dosage of a Y chromosome in a male of the same.7 Not only that, but with the sixty-plus years that have elapsed, we are much closer to understanding how such phenotypic effects due to “junk” or “selfish” DNA sequences take place. For one thing, it is now clear that different Y-chromosome sequence variants can differentially alter the expression of hundreds of genes in the somatic cells of male flies.8-10 For another, the characters that are affected are those of interest to the population geneticist — including such things as male reproductive traits. Then again, many of the genes so modulated by the Y chromosome in this Drosophila species are positioned in so-called “repressed” chromatin domains.11

A “Sink” that Titrates

Apropos is an in-press work by Emily Brown, Alison Nguyen, and Doris Bachtrog that tests a hypothesis to explain such Y-chromosomal-based phenotypic effects.12 Some have suggested that long stretches of repetitive elements on that chromosome (which again is millions of bases long) can serve as a “sink” that titrates out heterochromatic proteins, thereby depleting the latter in other domains of a nucleus.13 Congruent with this hypothesis, Brown and colleagues showed that a consequence of introducing a Y chromosome into a female, or by decreasing or increasing the copies or dosage of a Y chromosome in a male line, is a widespread redistribution in nuclei of histone markers that are specific for heterochromatin, but not for those that are specific for “active” euchromatin. This means that the Y-sequences do make their absence or presence and (if present) quantities “known” in morphogenesis. What is more, the balance of chromatin domains in female versus male flies is likely to be en masse modulated by such parameters.

We can thus rephrase what Doolittle and Sapienza or Orgel and Crick asserted back in 1980 in this manner: Seemingly “excess” nucleotides do have “phenotypic expressions” be they ever so indirect, which is to say that they do have “major effects on the phenotype.” It thus looks like there is a “why” to the fly “Y,” though it does not fit the axioms with which the “junk DNA” advocates beset us. Yet we should note that such a possibility was never actually excluded, for as Doolittle and Sapienza claimed: “We do not deny that…repetitive and unique-sequence DNAs not coding for protein in eukaryotes may have roles of immediate phenotypic benefit to the organism.”2    

References:

  1. Doolittle W.F., Sapienza C. 1980. Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601-603.  
  2. Orgel L.E., Crick F.H. 1980. Selfish DNA: the ultimate parasite. Nature 284: 604-607.
  3. Chang C.-H., Larracuente A.M. 2019. Heterochromatin-enriched assemblies reveal the sequence and organization of the Drosophila melanogaster Y chromosome. Genetics 211: 333-348.
  4. Gatti M., Pimpinelli S. 1983. Cytological and genetic analysis of the Y-chromosome of Drosophila melanogaster. 1. Organization of the fertility factors. Chromosoma 88: 349-373.  
  5. Bonaccorsi S., Lohe A. 1991. Fine mapping of satellite DNA sequences along the Y chromosome of Drosophila melanogaster: relationships between satellite sequences and fertility factors. Genetics 129: 177-189.
  6. Larracuente A.M., Clark A.G. 2013. Surprising differences in the variability of Y chromosomes in African and cosmopolitan populations of Drosophila melanogaster. Genetics 193: 201-214.
  7. Cooper, K.W. 1956. Phenotypic effects of Y chromosomal hyperploidy in Drosophila melanogaster, and their relation to variegation. Genetics 41: 242-264.
  8. Lemos B., Araripe L.O., Hartl D.L. 2008. Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences. Science 319: 91-93.
  9. Lemos B., Branco A.T., Hartl D.L. 2010. Epigenetic effects of polymorphic Y chromosomes modulate chromatin components, immune response, and sexual conflict. Proceedings of the National Academy of Science (U.S.A.) 107: 15826-15831.
  10. Sackton T.B., Montenegro H., Hartl D.L., Lemos B. 2011. Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila. Proceedings of the National Academy of Science (U.S.A.) 108: 17046-17051.
  11. Sackton T.B., Hartl D.L. 2013. Meta-analysis reveals that genes regulated by the Y chromosome in Drosophila melanogaster are preferentially localized to repressive chromatin. Genome Biology and Evolution 5: 255-266.
  12. Brown E.J., Nguyen A.H., Bachtrog D. 2020. The Drosophila Y chromosome affects heterochromatin integrity genome-wide. Molecular Biology and Evolution (in press).
  13. See references in Brown et al., 2020.

Photo: Drosophila melanogaster, an engaging fly, by Sanjay Acharya / CC BY-SA.