Drs David Miller and David Iles from the University of Leeds, in collaboration with Dr Martin Brinkworth at the University of Bradford, have found that sperm writes a DNA signature that can only be recognised by an egg from the same species. This enables fertilisation and may even explain how a species develops its own unique genetic identity.
Dr Iles says, "What we have discovered is a previously unrecognised DNA packaging 'signature' in mammalian sperm that may be essential for successful fertilisation of the egg and development of the embryo. We think it may also be ancient in origin."
Without the right 'key', successful fertilisation either cannot occur, or if it does, development will not proceed normally. Notably, disturbances in human sperm DNA packaging are known to cause male infertility and pregnancy failures.
This 'lock and key' mechanism has other profound implications. Not only does it explain why some otherwise healthy men produce sperm that is sterile, but it also explains how different species evolve and retain their own identity.
Says Dr Miller, "Up until now, Doctors have struggled to understand idiopathic male infertility. Our latest research offers a plausible explanation for why some sperm malfunction or fail to function correctly."
If the DNA carried by a sperm cell was unwound and stretched out, it would actually measure more than a metre in length. In order to fit all this DNA into the microscopic space within the head of the sperm cell, the DNA needs to be very tightly coiled, or packaged. The Leeds study showed that in human and mouse sperm, not all of the DNA is packaged in the same way. Whilst most of the paternal DNA is compressed in an extremely compact fashion, some is packaged less tightly.
"There is a definite pattern to the way DNA is packaged in sperm cells and we can see that this pattern is the same in unrelated fertile men. It is different in the sperm of infertile men. This implies that there is a significance to the packaging of DNA that has a direct relevance to male fertility," says Dr Iles.
Detailed analyses of the DNA in the 'open', less tightly packaged conformation, showed this DNA carries much of the information critical for activating genes essential for directing the development of the embryo. Further investigations showed the same conformation to exist in the sperm of several unrelated human donors and remarkably, highly similar packaging patterns to exist in the sperm of mice.
DNA regions in the 'open' conformation may therefore be more vulnerable to damaging toxins, such as those in cigarette smoke and certain anti-cancer drugs, than those that are tightly packaged. As Dr Brinkworth says, "this might mean that anything capable of causing genetic damage to sperm could have particular significance for the development of the embryo".
The findings also help explain why inter-species breeding is so rarely successful.
Where the locks and keys of two species do not match, however similar their DNA is, no viable offspring can be born. Occasionally, for example, with horses and donkeys, offspring are produced - but because the sperm and egg signatures are incompatible, their development as embryos is abnormal and any offspring are almost always infertile.
The research team believes that the same mechanism must also have played a role during human evolution. In the ancient history of mankind, Neanderthals co-existed with modern humans over many thousands of years. Sexual encounters between these two closely related species cannot be ruled out, yet there is no evidence in our DNA of a legacy from such couplings. It is possible that if offspring were produced, they either did not survive long or if they did, they were unable to breed.
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Tom Bennett, Royal Society (Mar 2017), £15,000
Jamie Johnston, Royal Society (Mar 2017), £15,000
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792
Richard Bayliss, Cancer Research UK (Jan 2017), £1,600,000
John Barr, EU (Jan 2017), £339,000
Mark Harris, Royal Society (Jan 2017), £250,000
Alison Dunn, NERC (Jan 2017), £105,000
Alex Breeze, Pancreatic Cancer Research Fund (Jan 2017), £180,000
Alison Dunn, NERC (Dec 2016), £18,000
Lisa Collins, BBSRC (Dec 2016), £1,681,835
Brendan Davies, Leverhulme Trust (Dec 2016), £247,555
Alan Benson, Mark Drinkhill, Ed White, British Heart Foundaion (Dec 2016), £217,223
Adrian Goldman, Royal Society (Dec 2016), £82,999
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, RCUK (Nov 2016), £484,172
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Katie Field, Rank Prize Funds (Nov 2016), £20,000
Jessica Kwok, Royal Society (Nov 2016), £14,948
John Ladbury, Cancer Research UK (Oct 2016), £4,250
Miriam Wittmann, Martin Stacey, Edward Vital, Lupus UK
(Oct 2016), £34,010
Valerie Speirs, NC3Rs
(Oct 2016), £90,000
Nicola Stonehouse, Morgan Herod, David Rowlands, BBSRC
(Sep 2016), £436,424
Joseph Cockburn, Wellcome Trust
(Sep 2016), £100,000
John Barr, Public Health England
(Sep 2016), £94,471
Helen Miller, DSM Nutritional Products A/S
(Sep 2016), £54,680
Steven Clapcote, Vitaflo International Ltd
(Sep 2016), £39,285
Juan Fontana Jordan De Urries
, Royal Society
(Sep 2016), £21,793
Jing Li, Sarah Calaghan, Mark Drinkhill, British Heart Foundation
(Sep 2016), £117,585
Sheena Radford, Alison Ashcroft, BBSRC (Sep 2016), £457,216
Patricija Van Oosten-Hawle, An-Jung Chen, David Westhead, NC3Rs
(Sep 2016), £354,456
Glyn Hemsworth, BBSRC (Sep 2016), £1,024,034
David Jayne, Paul Millner, MRC (Aug 2016), £207,860
Sheena Radford, Alison Ashcroft, BBSRC (Aug 2016), £457,215
Patricija Van Oosten-Hawle, Dave Westhead, An-Jung Chen, NC3Rs (Aug 2016), £354,456
Peter Henderson, EU - European Union
EU - European Union
(Jul 2016), £123,897
Adrian Goldman, EU - European Union
(Jul 2016), £116,290
Urwin, Howard Atkinson, NERC
(Jul 2016), £105,053
Eileen Ingham and colleagues in Engineering and M&H, EPSRC (Jul 2016), £3,867,449
Michael Colman, MRC (Jul 2016), £200,956
Tim Benton, Fresca Group Ltd
(Jul 2016), £52,082