April 16, 2002

Many things in life are apparently very true but, if repeatedly stated, could sound almost phony. I am now making this risk by repeating what Th. Dobzhansky has famously said - nothing in biology makes sense except in light of evolution. As a member of a genomics institute, it is worth the platitude because it is often under-appreciated how much evolutionary meaning there is in the deluge of genomic data. 

What does it mean when someone tells us that he/she is studying evolution? Our response would very likely be “evolution of what?” In other words, evolution is really a perspective rather than an object of study. One can be studying genetics, zoology, behavior, development or genomics with (or without) an evolutionary perspective but one does not study evolution per se.　

Why then do we need an evolutionary perspective? To make this point, I will use as an example the two major discoveries in science in the 19th century – Darwinism and Mendelism. The example is the first law of Mendelian genetics - the law of equal segregation. A male or female of the A/a genotype is expected to produce gametes of A and a type at equal proportion (and a Mendelian 1:2:1 ratio for the AA, Aa and aa genotypes ensues). The question an evolutionist should ask is why the segregation ratio is so often 1:1. Imagine that A is able to take advantage of the segregation and push the ratio in its own favor to, say, 10:1. In that case, allele A will spread in the population and allele a will disappear.  Allele A is cheating against the rule of Mendelian segregation.  Therefore, one might wonder whether Darwinism negates Mendelism.

A special case of Mendelian segregation is the sex ratio problem which troubled Darwin. Why do most species have female : male ratio at 1: 1? Is it not beneficial to the species to have more females since males are almost always in excess for the need of sperm supply of the species? 

How do we reconcile between the seeming discrepancy between Darwinism and Mendelism? It turns out that Darwinian selection does indeed lead to the Mendelian ratio of 1:1.　 The deviation from the 1:1 ratio is referred to as meiotic drive (meaning the cheating allele is driven to high frequency by meiosis-related mechanisms, rather than by selection). Most known meiotic drive systems consist of two very closely-linked loci which are so close that they look like a single locus. This is understandable as a one-locus drive system is difficult to achieve mechanistically. In a one-locus system, allele A has to destroy allele a. The same locus has to act both as an activator and as a receiver by, for example, requiring a protein to recognize its own DNA as a target. In reality, A usually targets an allele of a second locus, b, which is closely linked to the allele a. Hence, the pre-requisite of a meiotic drive system is that an activator locus finds a target locus nearby in the genome. This requirement reduces the chance of the violation of Mendelism. 

Still, such violations would occasionally emerge. What would happen then? It can be shown by a mathematical argument that any third locus that nullifies the meiotic drive would be favored by selection. (The detailed reasoning is rather complex and we shall forgo it for now.) The interesting part is that this third locus does not have to be physically close to the locus A and B. Let me use an analogy to explain the preservation of Mendelism by Dariwinism. The violation of Mendelism (cheating) can happen only between neighbors. When the cheating occasional arises, any third party, who may live anywhere, would be favored if it could suppress the cheating. In the end, Mendelism is preserved by Selectionism. For a side note, the first law of Mendelian genetics should be about “segregation”, rather than about “equal segregation”.　

The message is a simple one. Something as basic as the first law of Mendelian genetics is also the product of natural selection. One can study biology without an evolutionary perspective and, indeed, many biologists and medical professionals appear to do so. However, biology is much more interesting if seen through the prism of natural selection.