Genes' life stories unfold

A scanning electron micrograph of one of the seventeen fungal species analyzed in the study.
A scanning electron micrograph of one of the seventeen fungal species analyzed in the study.
Image courtesy of Janice Carr, Centers for Disease Control and Prevention

The wheels of evolution turn on genetic innovation — new genes with new functions appear, allowing organisms to grow and adapt in new ways. But deciphering the history of how and when various genes appeared, for any organism, has been a difficult and largely intractable task. A research team led by scientists at the Broad Institute of MIT and Harvard has broken new ground in this arena by developing a method, described in the September 6 advance online edition of Nature, that can reveal the ancestry of all genes across many different genomes. First applied to 17 species of fungi, the approach has unearthed some surprising clues about why new genes pop up in the first place and the biological nips and tucks that bolster their survival.

“Having the ability to trace the history of genes on a genomic scale opens the doors to a vast array of interesting and largely unexplored scientific questions,” said senior author Aviv Regev, a core member of the Broad Institute and an assistant professor of biology at MIT. “We have developed a method that accomplishes this task and applied it to seventeen different fungal species, which are separated by hundreds of millions of years of evolution. Theoretically, the method could be used to study any group of eukaryotic organisms.”

It has been recognized for decades that new genes are not created de novo, but instead first arise as carbon copies of existing genes. It is thought that this replication allows one of the gene copies to persist normally, while giving the other the freedom to acquire novel biological functions. Though the importance of this so-called gene duplication process is well appreciated — it is the grist for the mill of evolutionary change — the actual mechanics have remained murky, in part because scientists have lacked the tools to study it systematically.

Driven by the recent explosion of whole genome sequence data, the authors of the new study were able to assemble a natural history of more than 100,000 genes, belonging to a group of fungi known as the Ascomycota. From this, the researchers gained a detailed view of gene duplication across the genomes of 17 different species of fungi, including the laboratory model Saccharomyces cerevisiae, commonly known as baker’s yeast.

The basis for the work comes from a new method termed “SYNERGY”, which first author Ilan Wapinski and his coworkers developed to help them reconstruct the ancestry of each fungal gene. By tracing a gene’s lineage through various species, the method helps determine in which species the gene first arose, and if — and in what species — it became duplicated or even lost altogether. SYNERGY draws its strength from the use of multiple types of data, including the evolutionary or “phylogenetic” tree that depicts how species are related to each other, and the DNA sequences and relative positions of genes along the genome. Perhaps most importantly, the method does not tackle the problem of gene origins in one fell swoop, as has typically been done, but rather breaks it into discrete, more manageable bits. Instead of treating all species at once, SYNERGY first focuses on a pair of the most recently evolved species — those at the outer branches of the tree — and works, two-by-two, toward the more ancestral species that comprise the roots.

From this analysis, Regev and her colleagues were able to identify a set of core principles that govern gene duplication in fungi. One principle relates to the types of genes that tend to get duplicated. In sporadic gene duplication — that is, intermittent with respect to all of the genes in the genome — only a special portion of the fungal genome tends to be copied. This portion contains the genes that regulate the responses to stressful biological conditions. On the other hand, the so-called essential compartment, consisting primarily of genes that regulate growth, is rarely, if ever, duplicated.

Upon defining this rule, the researchers also uncovered its major exception, which occurs when the entire genome — the whole kit and caboodle — gets duplicated. Although such whole genome duplication (WGD) events are rare, they can be watershed moments evolutionarily speaking, allowing organisms to evolve in ways that might otherwise not have been possible. In the context of a WGD, the scientists discovered that growth-related genes in fact retain their duplicated status. Although the reason is not entirely clear, the researchers propose that genes involved in growth may normally be sensitive to biochemical imbalances, such as the one that ensues when only they themselves are duplicated. But, when all of their genomic companions get duplicated too, such a constraint might be lifted.

One of the researchers’ biggest surprises came from studying the fates of copied genes, regardless of whether it was in the context of a sporadic duplication or a sweeping, genome-wide one. The scientists’ expectation was that among the sets of copied genes, one copy, or paralog, would be free to take on new biological roles. It turns out, however, that fungal paralogs tend to diverge very little from one another and often remain virtually indistinguishable biochemically. Yet when the question was framed in terms of gene regulation — how and when gene copies are turned on and off — the answer turned out to be the opposite. Paralogs do diverge from each other, and in fact, can do so rather quickly, suggesting that it is easier to tweak genes’ regulation than their function.

Taken together, the findings begin to paint a picture of how new genes are groomed over hundreds of millions of years of evolution. Although the principles laid out in the study pertain to fungi, it is possible that they will have relevance to a variety of other species as well. And given the unpredicted findings that emerged from this initial, genome-wide analysis, subsequent work in other organisms has the potential to be equally, if not more, thought-provoking.

The Nature study was supported by grants from the Burroughs Wellcome Fund and the National Institute of General Medical Sciences.

Paper(s) cited

Wapinski et al. (2007) Natural history and evolutionary principles of gene duplication in fungi. Nature DOI:10.1038/nature06107