The evolution of a novel organism from the joining of 2 unmarried cells is a carefully orchestrated endeavor. But fifty-fifty before sperm meets egg, an every bit elaborate ready of choreographed steps must plough over off to ensure successful sexual reproduction. Those steps, known as reproductive jail cellular telephone sectionalization or meiosis, split upwardly the master copy number of chromosomes inward one-half hence that offspring volition inherit one-half their genetic fabric from 1 bring upwardly as well as one-half from the other.
During meiosis, each ready of homologous chromosomes couplet upwardly inward a form of chromosomal foursquare dance, chromosome 1 alongside chromosome 1, 2 alongside 2, as well as hence on downwards the line. The partners stick together, dancing through the phases of meiosis, until it is fourth dimension to segregate or separate to reverse ends of the dividing cell. When the dancers don't couplet or purpose appropriately it tin consequence inward eggs as well as sperm alongside the incorrect number of chromosomes, a major crusade of miscarriage as well as nascence defects.
To avoid these mistakes, nearly chromosomes usage a procedure known as crossing over, looping their arms alongside their partners as well as fifty-fifty swapping pieces of genetic fabric to stick together until the trip the lite fantastic toe is over. H5N1 few chromosomes, similar chromosome iv inward the fruit fly Drosophila melanogaster, are besides brusk to brand these crossovers. Yet somehow, they lead maintain figured out some other agency to remain connected to their partners.
Previously, Stacie E. Hughes, Ph.D., a enquiry specialist II at the Stowers Institute for Medical Research, identified sparse threads of deoxyribonucleic acid that seemed to necktie these other homologous chromosomes together. Yet a major query remained: in 1 lawsuit these chromosomes are roped into pairs, how practise they grapple to come upwardly apart again?
Now, Hughes as well as R. Scott Hawley, Ph.D., lead maintain shown that an enzyme called Topoisomerase II is required for resolving these threads hence homologous chromosomes tin purpose ways. The finding, published inward the Oct 23, 2014 number of PLoS Genetics, underscores the complexity of the meiotic process.
"It is non surprising in that place are many ways to segregate chromosomes because in that place are also many ways to command other molecular events, similar cistron expression," says Hawley, a Stowers Institute investigator as well as American Cancer Society enquiry professor. "This method of segregating shorter chromosomes may live clunky, odd, crazy, as well as as noncanonical as it gets, but that doesn't matter, because the cells survive. In the end, these processes don't lead maintain to live elegant, they just lead maintain to work."
Ever since Hughes' initial regain of deoxyribonucleic acid threads, she as well as Hawley lead maintain been looking for the molecular pair of scissors responsible for cutting entangled chromosomes free. The nearly prominent candidate to emerge from their search was Topoisomerase II, an enzyme known to cutting as well as untwist tangled strands of the double helix.
Previous enquiry had shown that Topisomerase II was involved inward before cellular processes similar deoxyribonucleic acid replication, as well as the enzyme was all the same detectable fifty-fifty during later on phases of meiosis. The researchers idea that Topoisomerase II mightiness live waiting around to practise yet some other job, cutting deoxyribonucleic acid threads to allow homologous chromosomes to segregate.
Testing their hypothesis seemed relatively straightforward. The researchers but needed to "knock out" Topoisomerase II inward their model organism of choice -- the woman individual fruit wing -- as well as and hence expect to regard whether meiosis was able to boot the bucket on usually without it. However, because the enzyme was involved inward hence many critical cellular processes, the researchers knew that such an approach would yield naught to a greater extent than than dead fruit flies.
Instead, they adapted a sophisticated method known as RNA interference -- which uses pocket-sized pieces of DNA's chemic cousin RNA to quiet genes -- as well as eliminated Topoisomerase II at a specific fourth dimension indicate belatedly inward meiosis. Hughes as well as hence isolated the oocytes from the fruit flies as well as analyzed them using fluorescent tags that illuminate the deoxyribonucleic acid threads connecting the chromosomes. Their findings were dramatic.
"Without this enzyme the chromosomes can't come upwardly apart, they are stuck together similar glue," says Hughes. "There are large regions of the chromosomes that are tethered together past times these threads, spell the balance is stretched out similar a slinky as the chromosomes are pulled inward reverse directions. It is just a mess. Because the chromosomes are just stuck there, they can't goal meiosis."
As a result, the mutant flies are essentially sterile. H5N1 separate study published inward the same magazine shows that manly individual mutants sense a similar fate, their spermatocytes permanently locked inward an young state. Without Topoisomerase II, the oocytes as well as spermatocytes are locked inward meiosis, unable to consummate the side past times side steps -- fertilization, jail cellular telephone sectionalization as well as differentiation -- needed to practise a novel organism.
The operate was funded inward purpose past times the Stowers Institute for Medical Research as well as the American Cancer Society (award number RP-05-086-06-DDC).
Summary of Findings
During the formation of eggs as well as sperm, the cell's chromosomes must couplet upwardly as well as purpose inward an elaborate sequence that results inward sexual practice cells alongside precisely one-half the number of chromosomes as the bring upwardly cell. H5N1 unmarried misstep tin crusade infertility, miscarriage, as well as nascence defects. Recent enquiry has shown that some chromosomes avoid these mistakes past times using sparse threads of deoxyribonucleic acid to tether themselves together, but how they come upwardly untied over again has non been clear. In the electrical current number of the scientific journalPLoS Genetics, Stowers Institute scientists written report that an enzyme called Topoisomerase II is required for these entangled chromosomes to live ready free. Stowers Research Associate II Stacie E. Hughes, Ph.D., who led the study, explains that without the enzyme, woman individual fruit flies were unable to consummate meiosis as well as were rendered completely sterile. Topoisomerase II probable resolves the deoxyribonucleic acid entanglements past times cutting as well as untwisting tangled DNA, as inward other processes similar deoxyribonucleic acid replication.