Last week we talked a bit about chromosomes, the process of sperm/egg/pollen formation, and how missteps during meiosis can lead to chromosomal mutations in terms of numbers of chromosomes. We defined haploidy and polyploidy as the loss or gain of an entire set of chromosomes, and monosomy and polysomy as the loss or gain of a single chromosome. We also saw how species and races contain variability, not just in the content of their DNA, but also in the number of chromosomes that they have. Humans, for instance, have one less chromosome than the other great apes; a single species of Iranian climbing weed has populations with vastly different numbers of chromosomes.
Today I’d like to continue following the layout of Dobzhansky’s book, Genetics and the Origin of Species, by continuing to categorize chromosomal mutations according to changes in their structure. Structural mutations do not affect the number of chromosomes within an organism, but rather alter the layout of genes within a chromosome. Structural mutations can be classified as follows:
1. Changes in the number of genes within a chromosome
a. Deletion (deficiency) à an entire gene, part of a gene, or a region of genes is lost from a chromosome. Remember that we have two copies of a single chromosome type; therefore an individual that has a deletion on one chromosome will still have one copy of the gene on the other chromosome, unless they inherit two chromosomes with the same deletion (which is likely in situations of inbreeding).
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| A deletion in the short arm of chromosome five in humans affects larynx development, giving affected babies a cat-like cry (hence the name 'cri-du-chat syndrome') |
b. Duplication à an entire gene, part of a gene, or a region of genes is present multiple times along a chromosome.
2. Changes in the location of genes within or between chromosomes
a. Inversion à A section of a chromosome rotates 180 degrees. For example, if genes were present along a chromosome in the order ABCDEFGHIJKL, an inversion would look like ABCJIHGFEDKL, with the inverted region in bold.
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| Inversions can lead to interesting chromosomal structures, as an inverted strand (AR) tries to find its complement in a noninverted strand (ST). Gene C on AR aligns with C on ST, D with D, etc, which is only possible by looping. |
b. Translocation (insertion) à The movement of genes from one chromosome to another
i. Simple translocation à Part of a chromosome breaks off and attaches to another chromosome
ii. Reciprocal or mutual translocations à two different chromosomes swap parts
The message I hope you take from this is that chromosomes are not static entities. They have the ability to change. Genes can ‘fall off’ one chromosome and attach to another; genes can break off and fail to attach, getting lost in the process; genes can flip around or insert themselves in new places or multiply within a chromosome. There are lots of interesting things that can happen within a chromosome, and these can drive new varieties.
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| The stripes in these corn kernels are due to jumping genes inserting themselves in genes responsible for colouration |
It is estimated that 50% of the human genome was created by jumping genes, but most of these are now inactive, or ‘fossilized’. But there is still a small subfamily, known as LINE-1, which are active in humans today. These LINE-1 jumping genes are astonishingly found in half a million different places within our chromosomes, sometimes right in the middle of a protein-coding gene. Amazingly, they do not just move themselves, but can carry other genes with them. They are active to the point that 1 in every 50 people so far examined carry within them a new insertion that was not found within their parents. If you are interested, you can read more here and here.
A related type of jumping gene, known as Alu, is found only in primates. Every human has approximately one million copies of Alu per cell, and it can be found inserted within nearly every primate gene. They are incapable of moving themselves and rely on LINE-1 jumping genes to propagate. An estimated 1 in every 200 humans acquire a new copy of Alu.
You would think that a bit of DNA inserting itself into a gene would be bad news, and indeed Alu has been implicated in some cancers. But the body can deal with at least some of these Alu insertions by simply removing them from the RNA. Here is how it works: many genes code for proteins. DNA is made up of four bases (A,C,T,G). A always binds with T, C always binds with G. DNA is double-stranded, with each strand being the mirror image of the other. A strand of ACAG would bind to TGTC, for example. Anyways, when a protein needs to be formed, the strands separate, and an enzyme docks on to the DNA to produce RNA. RNA also has four letters (A,C,U,G), with U substituting for T. Therefore RNA, which is single-stranded, becomes a mirror-copy of the DNA it was produced from. The RNA then is released from the DNA and eventually docks on to a ribosome, where every three letters of RNA code for a single amino acid in a protein. The ribosome reads the RNA and puts the protein together accordingly.
An Alu inserted into a gene would therefore produce a different, possibly non-functional, protein. And so there is a processing step that occurs before the RNA arrives at the ribosome. In this step, certain molecules cut up the RNA, remove certain pieces, and then put the RNA back together. These removed pieces, known as introns, often contain Alu inserts, among other things. The product is a garbage-free RNA molecule that can then perfectly code for a protein.
Amazingly, sometimes a single gene will code for multiple proteins, simply by having the RNA processed in different ways. Sometimes an intron will be removed, producing a ‘normal’ protein; sometimes it will be left in, producing a different protein. In this manner protein diversity can be greater than the number of genes.
And, it turns out, Alu is sometimes left in, thereby forming new proteins. It would seem, then, that Alu has been an important contributor to driving protein variation in humans.
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| Crossing-over during recombination |
There is another way in which chromosomes can change their structure apart from jumping genes. As we discovered last week, during meiosis the chromosome from your mom finds its partner from your dad and aligns in the middle of the cell. When they meet, these chromosome pairs (known as homologous chromosomes) actually join together to form a tetrad. This allows something known as recombination or, more ominously, crossing-over, to occur. Crossing-over is when a few of your mom’s alleles swap places with your dad’s alleles. If your mom and dad have identical alleles, nothing changes; if your mom had, say, an allele for blonde hair and your dad for brown hair, they may swap. This allows alleles to have new genetic backgrounds. For example, if your mom had a chromosome (and I am just making this up) that had an allele for blonde hair and an allele for tongue-rolling, and your dad’s chromosome had an allele for brown hair and an allele that inhibited tongue-rolling, crossing-over could produce a chromosome in which brown hair and tongue rolling are combined, and one in which blonde hair and the inability to roll one’s tongue are combined. New varieties are formed in this manner.
But, as is the case with meiosis in general, there can be breakdowns in crossing-over, which can lead to the formation of chromosomal mutations. If nonhomologous chromosomes align, sometimes they will swap genetic information. But this time, instead of different alleles of the same gene, they swap different genes entirely. In other cases, homologous chromosomes will swap alleles, but one may get a larger region of DNA than the other, leading to a deletion in one chromosome and a duplication in its partner. Sometimes the allele from one chromosomes is copied onto its homologous partner, without any alleles being exchanged. All of these produce new chromosomal varieties.
As with single-base mutations in genes, structural mutations in chromosomes are sometimes bad, but they can also be neutral or beneficial; their value depends, again, on the environment and their genetic background.
They are clearly common in nature. What, then, is their evolutionary significance? Come back next time for a discussion on natural variation and evolution.
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