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Gene Evolution Is All about Regulation

Okay, so gene evolution isn’t entirely about regulation. But protein-coding sequences of genes have changed comparatively little over hundreds of millions of years. When you look at the proteins that a human produces and compare them to the zebrafish, there are homologues (i.e., near matches) about 70% of the time [1]. The zebrafish has many duplicates of genes because of a massive duplication of its genome after our two lines split about 450 million years ago. But when you think that there’s roughly only about a 30% difference in the types of genes that our two species have, the level of conservation is astounding for the evolutionary span that separates us.

Danio rerio, the zebrafish.

Scientists believe therefore that the bulk of the differences between species, such as ourselves and zebrafish, lies largely within evolution of the DNA sequences that regulate gene expression. These variations in regulation can lead to changes in a variety of ways.

For one, there may be differences in the transcripts produced from a single gene, as well as how much of a given transcript is produced. Most genes produce multiple variations of the same gene, each one having modestly different functions. Variations in gene regulation can also lead to different expression patterns of a transcript across organs of the body or even adjacent tissues within the same organ, such as regions of the brain. And finally, gene regulation can alter patterns of the cell stages during which a gene transcript is expressed. This can lead, for instance, to variations in the structure of a tissue or organ. As an example, the differences between males and females are believed to be largely due to differences in the timing of specific gene expression between the sexes, as opposed to differences necessarily in kind [2].

Differences between species, therefore, are largely a matter of:

  1. What

  2. When

  3. Where

  4. How much

of a gene transcript is produced. There are many elements that work to control these expression patterns, and their numbers appear to increase as species complexity has increased. So, for instance, in the yeast genome, each gene has about 20 transcription factors that regulate it– while in humans there are twice as many. This increasing complexity has undoubtedly had exponential effects [3].

Many of the regulatory sequences in and surrounding genes are also well-conserved across species. These sequences can be sites for transcription factor binding as mentioned above, tethering sequences that help a factor locate its DNA target, insulators that keep adjacent elements from targeting the wrong regulatory sequence, and repressors that negatively regulate gene expression [3]. Many conserved regions of the DNA are also RNA genes, that don’t ultimately code for a protein but perform no-less-vital functions in cell metabolism. In fact, many non-coding RNA genes are thought to regulate protein-coding genes.

So you see, in spite of our focus for the last half century on the protein-coding sequences in the genome, it’s clear that these are in fact very well conserved across hundreds of millions of years. Which makes sense because they are so fundamental and the loss or duplication of a single protein-coding sequence can and usually does have disastrous effects on development. Instead, evolution has played around with subtler ways to regulate these same genes, and in doing so, has led to exceptional species variety. Thus, it’s not the number of building blocks you start out with, but what you do with them that counts.

#genehomologue #transposons #genes #mobileelements #zebrafish #genetics #ncRNA #geneexpression #epigenetics #proteincodinggenes #noncodingRNA #heterochrony #generegulation #transposableelements #development #DNA

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